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1. The arginine methyltransferase PRMT7 promotes extravasation of monocytes resulting in tissue injury in COPD

Author

Günes Günsel, Gizem, Conlon, Thomas M., Jeridi, Aicha, Kim, Rinho, Ertüz, Zeynep, Lang, Niklas J., Ansari, Meshal, Novikova, Mariia, Jiang, Dongsheng, Strunz, Maximilian, Gaianova, Mariia, Hollauer, Christine, Gabriel, Christina, Angelidis, Ilias, Doll, Sebastian, Pestoni, Jeanine C., Edelmann, Stephanie L., Kohlhepp, Marlene Sophia, Guillot, Adrien, Bassler, Kevin, Van Eeckhoutte, Hannelore P., Kayalar, Özgecan, Konyalilar, Nur, Kanashova, Tamara, Rodius, Sophie, Ballester-López, Carolina, Genes Robles, Carlos M., Smirnova, Natalia, Rehberg, Markus, Agarwal, Charu, Krikki, Ioanna, Piavaux, Benoit, Verleden, Stijn E., Vanaudenaerde, Bart, Königshoff, Melanie, Dittmar, Gunnar, Bracke, Ken R., Schultze, Joachim L., Watz, Henrik, Eickelberg, Oliver, Stoeger, Tobias, Burgstaller, Gerald, Tacke, Frank, Heissmeyer, Vigo, Rinkevich, Yuval, Bayram, Hasan, Schiller, Herbert B., Conrad, Marcus, Schneider, Robert, and Yildirim, Ali Önder

Published
2022
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3. Stable Isotope-Assisted Untargeted Metabolomics Identifies ALDH1A1-Driven Erythronate Accumulation in Lung Cancer Cells

Author

Zhang, Jie, primary, Keibler, Mark A., additional, Dong, Wentao, additional, Ghelfi, Jenny, additional, Cordes, Thekla, additional, Kanashova, Tamara, additional, Pailot, Arnaud, additional, Linster, Carole L., additional, Dittmar, Gunnar, additional, Metallo, Christian M., additional, Lautenschlaeger, Tim, additional, Hiller, Karsten, additional, and Stephanopoulos, Gregory, additional

Published
2023
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4. Effect of Atmospheric Aging on Soot Particle Toxicity in Lung Cell Models at the Air-Liquid Interface: Differential Toxicological Impacts of Biogenic and Anthropogenic Secondary Organic Aerosols (SOAs)

Author

Offer, Svenja, Hartner, Elena, Bucchianico, Sebastiano Di, Bisig, Christoph, Bauer, Stefanie, Pantzke, Jana, Zimmermann, Elias J., Cao, Xin, Binder, Stefanie, Kuhn, Evelyn, Huber, Anja, Jeong, Seongho, Kafer, Uwe, Martens, Patrick, Mesceriakovas, Arunas, Bendl, Jan, Brejcha, Ramona, Buchholz, Angela, Gat, Daniella, Hohaus, Thorsten, Rastak, Narges, Jakobi, Gert, Kalberer, Markus, Kanashova, Tamara, Hu, Yue, Ogris, Christoph, Marsico, Annalisa, Theis, Fabian, Pardo, Michal, Groger, Thomas, Oeder, Sebastian, Orasche, Jurgen, Paul, Andreas, Ziehm, Till, Zhang, Zhi-Hui, Adam, Thomas, Sippula, Olli, Sklorz, Martin, Schnelle-Kreis, Jurgen, Czech, Hendryk, Kiendler-Scharr, Astrid, Rudich, Yinon, and Zimmermann, Ralf

Subjects
Lung diseases -- Risk factors -- Development and progression, Aerosols -- Environmental aspects -- Health aspects, Air pollution -- Health aspects, Soot -- Environmental aspects -- Health aspects, Environmental issues, Health
Abstract

Background: Secondary organic aerosols (SOAs) formed from anthropogenic or biogenic gaseous precursors in the atmosphere substantially contribute to the ambient fine particulate matter [PM [less than or equal to] 2.5 [micro]m in aerodynamic diameter (P[M.sub.2.5])] burden, which has been associated with adverse human health effects. However, there is only limited evidence on their differential toxicological impact. OBJECTIVES: We aimed to discriminate toxicological effects of aerosols generated by atmospheric aging on combustion soot particles (SPs) of gaseous biogenic ([beta]-pinene) or anthropogenic (naphthalene) precursors in two different lung cell models exposed at the air-liquid interface (ALI). Methods: Mono- or cocultures of lung epithelial cells (A549) and endothelial cells (EA.hy926) were exposed at the ALI for 4 h to different aerosol concentrations of a photochemically aged mixture of primary combustion SP and [beta]-pinene ([SOA.sub.[beta]PIN]-SP) or naphthalene ([SOA.sub.NAP]-SP). The internally mixed soot/SOA particles were comprehensively characterized in terms of their physical and chemical properties. We conducted toxicity tests to determine cytotoxicity, intracellular oxidative stress, primary and secondary genotoxicity, as well as inflammatory and angiogenic effects. Results: We observed considerable toxicity-related outcomes in cells treated with either SOA type. Greater adverse effects were measured for [SOA.sub.NAP]-SP compared with [SOA.sub.[beta]PIN]-SP in both cell models, whereas the nano-sized soot cores alone showed only minor effects. At the functional level, we found that [SOA.sub.NAP]-SP augmented the secretion of malondialdehyde and interleukin-8 and may have induced the activation of endothelial cells in the coculture system. This activation was confirmed by comet assay, suggesting secondary genotoxicity and greater angiogenic potential. Chemical characterization of PM revealed distinct qualitative differences in the composition of the two secondary aerosol types. Discussion: In this study using A549 and EA.hy926 cells exposed at ALI, SOA compounds had greater toxicity than primary SPs. Photochemical aging of naphthalene was associated with the formation of more oxidized, more aromatic SOAs with a higher oxidative potential and toxicity compared with [beta]-pinene. Thus, we conclude that the influence of atmospheric chemistry on the chemical PM composition plays a crucial role for the adverse health outcome of emissions. https://doi.org/10.1289/EHP9413, Introduction Over the past decades, the impact of ambient fine particulate matter [PM [less than or equal to] 2.5 [micro]m (P[M.sub.2.5])] on the global burden of disease has gained substantial [...]

Published
2022
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5. Influence of wood species on toxicity of log-wood stove combustion aerosols: a parallel animal and air-liquid interface cell exposure study on spruce and pine smoke

Author

Ihantola, Tuukka, Di Bucchianico, Sebastiano, Happo, Mikko, Ihalainen, Mika, Uski, Oskari, Bauer, Stefanie, Kuuspalo, Kari, Sippula, Olli, Tissari, Jarkko, Oeder, Sebastian, Hartikainen, Anni, Rönkkö, Teemu J., Martikainen, Maria-Viola, Huttunen, Kati, Vartiainen, Petra, Suhonen, Heikki, Kortelainen, Miika, Lamberg, Heikki, Leskinen, Ari, Sklorz, Martin, Michalke, Bernhard, Dilger, Marco, Weiss, Carsten, Dittmar, Gunnar, Beckers, Johannes, Irmler, Martin, Buters, Jeroen, Candeias, Joana, Czech, Hendryk, Yli-Pirilä, Pasi, Abbaszade, Gülcin, Jakobi, Gert, Orasche, Jürgen, Schnelle-Kreis, Jürgen, Kanashova, Tamara, Karg, Erwin, Streibel, Thorsten, Passig, Johannes, Hakkarainen, Henri, Jokiniemi, Jorma, Zimmermann, Ralf, Hirvonen, Maija-Riitta, and Jalava, Pasi I.

Published
2020
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6. Senescence-associated reprogramming promotes cancer stemness

Author

Milanovic, Maja, Fan, Dorothy N. Y., Belenki, Dimitri, Dbritz, J. Henry M., Zhao, Zhen, Yu, Yong, Drr, Jan R., Dimitrova, Lora, Lenze, Dido, Monteiro Barbosa, Ines A., Mendoza-Parra, Marco A., Kanashova, Tamara, Metzner, Marlen, Pardon, Katharina, Reimann, Maurice, Trumpp, Andreas, Drken, Bernd, Zuber, Johannes, Gronemeyer, Hinrich, Hummel, Michael, Dittmar, Gunnar, Lee, Soyoung, and Schmitt, Clemens A.

Subjects
Cancer -- Physiological aspects, Aging (Biology) -- Health aspects, Cancer cells -- Physiological aspects, Stem cells -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Maja Milanovic [1]; Dorothy N. Y. Fan [1, 2, 3, 4]; Dimitri Belenki [1]; J. Henry M. Dbritz [1]; Zhen Zhao [5]; Yong Yu [6]; Jan R. Drr [1]; [...]

Published
2018
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7. Stable Isotope-Assisted Untargeted Metabolomics Identifies ALDH1A1-Driven Erythronate Accumulation in Lung Cancer Cells

Author

Massachusetts Institute of Technology. Department of Chemical Engineering, Zhang, Jie, Keibler, Mark A., Dong, Wentao, Ghelfi, Jenny, Cordes, Thekla, Kanashova, Tamara, Pailot, Arnaud, Linster, Carole L., Dittmar, Gunnar, Metallo, Christian M., Lautenschlaeger, Tim, Hiller, Karsten, Stephanopoulos, Gregory, Massachusetts Institute of Technology. Department of Chemical Engineering, Zhang, Jie, Keibler, Mark A., Dong, Wentao, Ghelfi, Jenny, Cordes, Thekla, Kanashova, Tamara, Pailot, Arnaud, Linster, Carole L., Dittmar, Gunnar, Metallo, Christian M., Lautenschlaeger, Tim, Hiller, Karsten, and Stephanopoulos, Gregory

Abstract

Using an untargeted stable isotope-assisted metabolomics approach, we identify erythronate as a metabolite that accumulates in several human cancer cell lines. Erythronate has been reported to be a detoxification product derived from off-target glycolytic metabolism. We use chemical inhibitors and genetic silencing to define the pentose phosphate pathway intermediate erythrose 4-phosphate (E4P) as the starting substrate for erythronate production. However, following enzyme assay-coupled protein fractionation and subsequent proteomics analysis, we identify aldehyde dehydrogenase 1A1 (ALDH1A1) as the predominant contributor to erythrose oxidation to erythronate in cell extracts. Through modulating ALDH1A1 expression in cancer cell lines, we provide additional support. We hence describe a possible alternative route to erythronate production involving the dephosphorylation of E4P to form erythrose, followed by its oxidation by ALDH1A1. Finally, we measure increased erythronate concentrations in tumors relative to adjacent normal tissues from lung cancer patients. These findings suggest the accumulation of erythronate to be an example of metabolic reprogramming in cancer cells, raising the possibility that elevated levels of erythronate may serve as a biomarker of certain types of cancer.

Published
2023

8. Non-targeted metabolomics identifies erythronate accumulation in cancer cells

Author

Zhang, Jie, primary, Keibler, Mark A., additional, Dong, Wentao, additional, Ghelfi, Jenny, additional, Cordes, Thekla, additional, Kanashova, Tamara, additional, Pailot, Arnaud, additional, Linster, Carole, additional, Dittmar, Gunnar, additional, Metallo, Christian M., additional, Lautenschlaeger, Tim, additional, Hiller, Karsten, additional, and Stephanopoulos, Gregory, additional

Published
2022
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9. Exposure to naphthalene and β-pinene-derived secondary organic aerosol induced divergent changes in transcript levels of BEAS-2B cells

Author

Pardo, Michal, primary, Offer, Svenja, additional, Hartner, Elena, additional, Di Bucchianico, Sebastiano, additional, Bisig, Christoph, additional, Bauer, Stefanie, additional, Pantzke, Jana, additional, Zimmermann, Elias J., additional, Cao, Xin, additional, Binder, Stephanie, additional, Kuhn, Evelyn, additional, Huber, Anja, additional, Jeong, Seongho, additional, Käfer, Uwe, additional, Schneider, Eric, additional, Mesceriakovas, Arunas, additional, Bendl, Jan, additional, Brejcha, Ramona, additional, Buchholz, Angela, additional, Gat, Daniela, additional, Hohaus, Thorsten, additional, Rastak, Narges, additional, Karg, Erwin, additional, Jakobi, Gert, additional, Kalberer, Markus, additional, Kanashova, Tamara, additional, Hu, Yue, additional, Ogris, Christoph, additional, Marsico, Annalisa, additional, Theis, Fabian, additional, Shalit, Tali, additional, Gröger, Thomas, additional, Rüger, Christopher P., additional, Oeder, Sebastian, additional, Orasche, Jürgen, additional, Paul, Andreas, additional, Ziehm, Till, additional, Zhang, Zhi-Hui, additional, Adam, Thomas, additional, Sippula, Olli, additional, Sklorz, Martin, additional, Schnelle-Kreis, Jürgen, additional, Czech, Hendryk, additional, Kiendler-Scharr, Astrid, additional, Zimmermann, Ralf, additional, and Rudich, Yinon, additional

Published
2022
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12. Additional file 8 of Influence of wood species on toxicity of log-wood stove combustion aerosols: a parallel animal and air-liquid interface cell exposure study on spruce and pine smoke

Author

Ihantola, Tuukka, Bucchianico, Sebastiano Di, Happo, Mikko, Ihalainen, Mika, Uski, Oskari, Bauer, Stefanie, Kuuspalo, Kari, Sippula, Olli, Tissari, Jarkko, Oeder, Sebastian, Hartikainen, Anni, Rönkkö, Teemu J., Maria-Viola Martikainen, Huttunen, Kati, Vartiainen, Petra, Suhonen, Heikki, Kortelainen, Miika, Lamberg, Heikki, Leskinen, Ari, Sklorz, Martin, Michalke, Bernhard, Dilger, Marco, Weiss, Carsten, Dittmar, Gunnar, Beckers, Johannes, Irmler, Martin, Buters, Jeroen, Candeias, Joana, Hendryk Czech, Yli-Pirilä, Pasi, Gülcin Abbaszade, Jakobi, Gert, Orasche, Jürgen, Schnelle-Kreis, Jürgen, Kanashova, Tamara, Karg, Erwin, Streibel, Thorsten, Passig, Johannes, Hakkarainen, Henri, Jokiniemi, Jorma, Zimmermann, Ralf, Maija-Riitta Hirvonen, and Jalava, Pasi I.

Subjects
respiratory system, respiratory tract diseases
Abstract

Additional file 8 Figure S4. Viability (A), Comet assay (B) and IL-8 secretion (C) of A549 control cells after exposed one hour at incubator with CO2, incubator without CO2 or Tox-ALI to clean air. Each bar shows mean ± SEM, n = 3.

Published
2020
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13. Additional file 4 of Influence of wood species on toxicity of log-wood stove combustion aerosols: a parallel animal and air-liquid interface cell exposure study on spruce and pine smoke

Author

Ihantola, Tuukka, Bucchianico, Sebastiano Di, Happo, Mikko, Ihalainen, Mika, Uski, Oskari, Bauer, Stefanie, Kuuspalo, Kari, Sippula, Olli, Tissari, Jarkko, Oeder, Sebastian, Hartikainen, Anni, Rönkkö, Teemu J., Maria-Viola Martikainen, Huttunen, Kati, Vartiainen, Petra, Suhonen, Heikki, Kortelainen, Miika, Lamberg, Heikki, Leskinen, Ari, Sklorz, Martin, Michalke, Bernhard, Dilger, Marco, Weiss, Carsten, Dittmar, Gunnar, Beckers, Johannes, Irmler, Martin, Buters, Jeroen, Candeias, Joana, Hendryk Czech, Yli-Pirilä, Pasi, Gülcin Abbaszade, Jakobi, Gert, Orasche, Jürgen, Schnelle-Kreis, Jürgen, Kanashova, Tamara, Karg, Erwin, Streibel, Thorsten, Passig, Johannes, Hakkarainen, Henri, Jokiniemi, Jorma, Zimmermann, Ralf, Maija-Riitta Hirvonen, and Jalava, Pasi I.

Abstract

Additional file 4 Figure S2. Size of the particles measured by SMPS per day to day. The geometric mean diameters are shown with the solid lines, while GSDs are represented with dashed lines. (average of 3 experiments)

Published
2020
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14. Additional file 7 of Influence of wood species on toxicity of log-wood stove combustion aerosols: a parallel animal and air-liquid interface cell exposure study on spruce and pine smoke

Author

Ihantola, Tuukka, Bucchianico, Sebastiano Di, Happo, Mikko, Ihalainen, Mika, Uski, Oskari, Bauer, Stefanie, Kuuspalo, Kari, Sippula, Olli, Tissari, Jarkko, Oeder, Sebastian, Hartikainen, Anni, Rönkkö, Teemu J., Maria-Viola Martikainen, Huttunen, Kati, Vartiainen, Petra, Suhonen, Heikki, Kortelainen, Miika, Lamberg, Heikki, Leskinen, Ari, Sklorz, Martin, Michalke, Bernhard, Dilger, Marco, Weiss, Carsten, Dittmar, Gunnar, Beckers, Johannes, Irmler, Martin, Buters, Jeroen, Candeias, Joana, Hendryk Czech, Yli-Pirilä, Pasi, Gülcin Abbaszade, Jakobi, Gert, Orasche, Jürgen, Schnelle-Kreis, Jürgen, Kanashova, Tamara, Karg, Erwin, Streibel, Thorsten, Passig, Johannes, Hakkarainen, Henri, Jokiniemi, Jorma, Zimmermann, Ralf, Maija-Riitta Hirvonen, and Jalava, Pasi I.

Abstract

Additional file 7 Table S3. Inorganic elements from spruce and pine combustion emissions. Organic compounds were sampled over 4-h exposure. Concentrations are calculated as averages from three test cycles ± standard deviation.

Published
2020
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15. Additional file 9 of Influence of wood species on toxicity of log-wood stove combustion aerosols: a parallel animal and air-liquid interface cell exposure study on spruce and pine smoke

Author

Ihantola, Tuukka, Bucchianico, Sebastiano Di, Happo, Mikko, Ihalainen, Mika, Uski, Oskari, Bauer, Stefanie, Kuuspalo, Kari, Sippula, Olli, Tissari, Jarkko, Oeder, Sebastian, Hartikainen, Anni, Rönkkö, Teemu J., Maria-Viola Martikainen, Huttunen, Kati, Vartiainen, Petra, Suhonen, Heikki, Kortelainen, Miika, Lamberg, Heikki, Leskinen, Ari, Sklorz, Martin, Michalke, Bernhard, Dilger, Marco, Weiss, Carsten, Dittmar, Gunnar, Beckers, Johannes, Irmler, Martin, Buters, Jeroen, Candeias, Joana, Hendryk Czech, Yli-Pirilä, Pasi, Gülcin Abbaszade, Jakobi, Gert, Orasche, Jürgen, Schnelle-Kreis, Jürgen, Kanashova, Tamara, Karg, Erwin, Streibel, Thorsten, Passig, Johannes, Hakkarainen, Henri, Jokiniemi, Jorma, Zimmermann, Ralf, Maija-Riitta Hirvonen, and Jalava, Pasi I.

Abstract

Additional file 9 Table S4. Top 5 significant ingenuity canonical pathways of spruce aerosol exposure.

Published
2020
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16. Additional file 5 of Influence of wood species on toxicity of log-wood stove combustion aerosols: a parallel animal and air-liquid interface cell exposure study on spruce and pine smoke

Author

Ihantola, Tuukka, Bucchianico, Sebastiano Di, Happo, Mikko, Ihalainen, Mika, Uski, Oskari, Bauer, Stefanie, Kuuspalo, Kari, Sippula, Olli, Tissari, Jarkko, Oeder, Sebastian, Hartikainen, Anni, Rönkkö, Teemu J., Maria-Viola Martikainen, Huttunen, Kati, Vartiainen, Petra, Suhonen, Heikki, Kortelainen, Miika, Lamberg, Heikki, Leskinen, Ari, Sklorz, Martin, Michalke, Bernhard, Dilger, Marco, Weiss, Carsten, Dittmar, Gunnar, Beckers, Johannes, Irmler, Martin, Buters, Jeroen, Candeias, Joana, Hendryk Czech, Yli-Pirilä, Pasi, Gülcin Abbaszade, Jakobi, Gert, Orasche, Jürgen, Schnelle-Kreis, Jürgen, Kanashova, Tamara, Karg, Erwin, Streibel, Thorsten, Passig, Johannes, Hakkarainen, Henri, Jokiniemi, Jorma, Zimmermann, Ralf, Maija-Riitta Hirvonen, and Jalava, Pasi I.

Abstract

Additional file 5 Figure S3. Size of the particles measured by SMPS. The geometric mean diameters (a) and mass median diameters (b) are shown with the solid lines, while GSDs are represented with dashed lines. Average of 3 experiments.

Published
2020
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17. Additional file 11 of Influence of wood species on toxicity of log-wood stove combustion aerosols: a parallel animal and air-liquid interface cell exposure study on spruce and pine smoke

Author

Ihantola, Tuukka, Bucchianico, Sebastiano Di, Happo, Mikko, Ihalainen, Mika, Uski, Oskari, Bauer, Stefanie, Kuuspalo, Kari, Sippula, Olli, Tissari, Jarkko, Oeder, Sebastian, Hartikainen, Anni, Rönkkö, Teemu J., Maria-Viola Martikainen, Huttunen, Kati, Vartiainen, Petra, Suhonen, Heikki, Kortelainen, Miika, Lamberg, Heikki, Leskinen, Ari, Sklorz, Martin, Michalke, Bernhard, Dilger, Marco, Weiss, Carsten, Dittmar, Gunnar, Beckers, Johannes, Irmler, Martin, Buters, Jeroen, Candeias, Joana, Hendryk Czech, Yli-Pirilä, Pasi, Gülcin Abbaszade, Jakobi, Gert, Orasche, Jürgen, Schnelle-Kreis, Jürgen, Kanashova, Tamara, Karg, Erwin, Streibel, Thorsten, Passig, Johannes, Hakkarainen, Henri, Jokiniemi, Jorma, Zimmermann, Ralf, Maija-Riitta Hirvonen, and Jalava, Pasi I.

Abstract

Additional file 11 Figure S5. Area under curve (AUC) calculated from exposed A549 cells from three different timepoints of H2DCFDA measurements. Each bar shows mean ± SEM, n = 3.

Published
2020
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18. An Integrative Workflow to Prioritize Toxicity Initiation Events From Air-liquid-interface Exposure of Human Lung Cells to Combustion Aerosols: First Application to Emissions From a Heavy Fuel Oil or Diesel Fuel Operated Ship Engine

Author

Gupta, Suchi Smita, primary, Orasche, Jürgen, additional, Streibel, Thorsten, additional, Passig, Johannes, additional, Czech, Hendryk, additional, Schnelle-Kreis, Jürgen, additional, Sklorz, Martin, additional, Sippula, Olli, additional, Jokiniemi, Jorma, additional, Hirvonen, Maija-Riitta, additional, Dittmar, Gunnar, additional, Kanashova, Tamara, additional, Öder, Sebastian, additional, Buters, Jeroen, additional, Stengel, Benjamin, additional, Harndorf, Horst, additional, Dilger, Marco, additional, Schlager, Christoph, additional, Hiller, Karsten, additional, Sapcariou, Sean, additional, Gupta, Shailendra, additional, Wolkenhauer, Olaf, additional, and Zimmermann, Ralf, additional

Published
2021
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23. Muscle RING‐finger 2 and 3 maintain striated‐muscle structure and function

Author

Lodka, Dörte, Pahuja, Aanchal, Geers‐Knörr, Cornelia, Scheibe, Renate J., Nowak, Marcel, Hamati, Jida, Köhncke, Clemens, Purfürst, Bettina, Kanashova, Tamara, Schmidt, Sibylle, Glass, David J., Morano, Ingo, Heuser, Arnd, Kraft, Theresia, Bassel‐Duby, Rhonda, Olson, Eric N., Dittmar, Gunnar, Sommer, Thomas, and Fielitz, Jens

Subjects
MAPKAPK, Protein surplus myopathy, Original Article, Heart failure, Original Articles, Protein homeostasis, MuRF2, MuRF3
Abstract

Background The Muscle‐specific RING‐finger (MuRF) protein family of E3 ubiquitin ligases is important for maintenance of muscular structure and function. MuRF proteins mediate adaptation of striated muscles to stress. MuRF2 and MuRF3 bind to microtubules and are implicated in sarcomere formation with noticeable functional redundancy. However, if this redundancy is important for muscle function in vivo is unknown. Our objective was to investigate cooperative function of MuRF2 and MuRF3 in the skeletal muscle and the heart in vivo. Methods MuRF2 and MuRF3 double knockout mice (DKO) were generated and phenotypically characterized. Skeletal muscle and the heart were investigated by morphological measurements, histological analyses, electron microscopy, immunoblotting, and real‐time PCR. Isolated muscles were subjected to in vitro force measurements. Cardiac function was determined by echocardiography and working heart preparations. Function of cardiomyocytes was measured in vitro. Cell culture experiments and mass‐spectrometry were used for mechanistic analyses. Results DKO mice showed a protein aggregate myopathy in skeletal muscle. Maximal force development was reduced in DKO soleus and extensor digitorum longus. Additionally, a fibre type shift towards slow/type I fibres occurred in DKO soleus and extensor digitorum longus. MuRF2 and MuRF3‐deficient hearts showed decreased systolic and diastolic function. Further analyses revealed an increased expression of the myosin heavy chain isoform beta/slow and disturbed calcium handling as potential causes for the phenotype in DKO hearts. Conclusions The redundant function of MuRF2 and MuRF3 is important for maintenance of skeletal muscle and cardiac structure and function in vivo.

Published
2015

24. Particulate Matter from Both Heavy Fuel Oil and Diesel Fuel Shipping Emissions Show Strong Biological Effects on Human Lung Cells at Realistic and Comparable In Vitro Exposure Conditions

Author

Oeder Sebastian, Kanashova Tamara, Sippula Olli, Sapcariu Sean C., Streibel Thorsten, Arteaga-Salas Jose Manuel, Passig Johannes, Dilger Marco, Paur Hanns-Rudolf, Schlager Christoph, Mulhopt Sonja, Diabate Silvia, Weiss Carsten, Stengel Benjamin, Rabe Rom, Harndorf Horst, Torvela Tiina, Jokiniemi Jorma K., Hirvonen Maija-Riitta, Schmidt-Weber Carsten, Traidl-Hoffmann Claudia, Berube Kelly A., Wlodarczyk Anna J., Prytherch Zoe, and Michalke Bernhard

Published
2015
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27. Senescence-associated reprogramming promotes cancer stemness

Author

Milanovic, Maja, primary, Fan, Dorothy N. Y., additional, Belenki, Dimitri, additional, Däbritz, J. Henry M., additional, Zhao, Zhen, additional, Yu, Yong, additional, Dörr, Jan R., additional, Dimitrova, Lora, additional, Lenze, Dido, additional, Monteiro Barbosa, Ines A., additional, Mendoza-Parra, Marco A., additional, Kanashova, Tamara, additional, Metzner, Marlen, additional, Pardon, Katharina, additional, Reimann, Maurice, additional, Trumpp, Andreas, additional, Dörken, Bernd, additional, Zuber, Johannes, additional, Gronemeyer, Hinrich, additional, Hummel, Michael, additional, Dittmar, Gunnar, additional, Lee, Soyoung, additional, and Schmitt, Clemens A., additional

Published
2017
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30. Particulate Matter from Both Heavy Fuel Oil and Diesel Fuel Shipping Emissions Show Strong Biological Effects on Human Lung Cells at Realistic and Comparable In Vitro Exposure Conditions

Author

Oeder, Sebastian, Kanashova, Tamara, Sippula, Olli, Sapcariu, Sean C., Streibel, Thorsten, Arteaga-Salas, Jose Manuel, Passig, Johannes, Dilger, Marco, Paur, Hanns-Rudolf, Schlager, Christoph, Mülhopt, Sonja, Diabaté, Silvia, Weiss, Carsten, Stengel, Benjamin, Rabe, Rom, Harndorf, Horst, Torvela, Tiina, Jokiniemi, Jorma K., Hirvonen, Maija-Riitta, Schmidt-Weber, Carsten, Traidl-Hoffmann, Claudia, BéruBé, Kelly A., Wlodarczyk, Anna J., Prytherch, Zoë, Michalke, Bernhard, Krebs, Tobias, Prévôt, André S. H., Kelbg, Michael, Tiggesbäumker, Josef, Karg, Erwin, Jakobi, Gert, Scholtes, Sorana, Schnelle-Kreis, Jürgen, Lintelmann, Jutta, Matuschek, Georg, Sklorz, Martin, Klingbeil, Sophie, Orasche, Jürgen, Richthammer, Patrick, Müller, Laarnie, Elsasser, Michael, Reda, Ahmed, Gröger, Thomas, Weggler, Benedikt, Schwemer, Theo, Czech, Hendryk, Rüger, Christopher P., Abbaszade, Gülcin, Radischat, Christian, Hiller, Karsten, Buters, Jeroen T. M., Dittmar, Gunnar, and Zimmermann, Ralf

Subjects
ddc
Published
2015

31. Metabolic Profiling as Well as Stable Isotope Assisted Metabolic and Proteomic Analysis of RAW 264.7 Macrophages Exposed to Ship Engine Aerosol Emissions: Different Effects of Heavy Fuel Oil and Refined Diesel Fuel.

Author

Sapcariu, Sean, Kanashova, Tamara, Dilger, Marco, Diabate, Silvia, Oeder, Sebastian, Passig, Johannes, Radischat, Christian, Buters, Jeroen, Sippula, Olli, Streibel, Thorsten, Paur, Hanns-Rudolf, Schlager, Christoph, Mulhopt, Sonja, Stengel, Benjamin, Rabe, Rom, Harndorf, Horst, Krebs, Tobias, Karg, Erwin, Groger, Thomas, Weiss, Carsten, Dittmar, Gunnar, Hiller, Karsten, Zimmermann, Ralf, Sapcariu, Sean, Kanashova, Tamara, Dilger, Marco, Diabate, Silvia, Oeder, Sebastian, Passig, Johannes, Radischat, Christian, Buters, Jeroen, Sippula, Olli, Streibel, Thorsten, Paur, Hanns-Rudolf, Schlager, Christoph, Mulhopt, Sonja, Stengel, Benjamin, Rabe, Rom, Harndorf, Horst, Krebs, Tobias, Karg, Erwin, Groger, Thomas, Weiss, Carsten, Dittmar, Gunnar, Hiller, Karsten, and Zimmermann, Ralf

Abstract

Exposure to air pollution resulting from fossil fuel combustion has been linked to multiple short-term and long term health effects. In a previous study, exposure of lung epithelial cells to engine exhaust from heavy fuel oil (HFO) and diesel fuel (DF), two of the main fuels used in marine engines, led to an increased regulation of several pathways associated with adverse cellular effects, including pro-inflammatory pathways. In addition, DF exhaust exposure was shown to have a wider response on multiple cellular regulatory levels compared to HFO emissions, suggesting a potentially higher toxicity of DF emissions over HFO. In order to further understand these effects, as well as to validate these findings in another cell line, we investigated macrophages under the same conditions as a more inflammation-relevant model. An air-liquid interface aerosol exposure system was used to provide a more biologically relevant exposure system compared to submerged experiments, with cells exposed to either the complete aerosol (particle and gas phase), or the gas phase only (with particles filtered out). Data from cytotoxicity assays were integrated with metabolomics and proteomics analyses, including stable isotope-assisted metabolomics, in order to uncover pathways affected by combustion aerosol exposure in macrophages. Through this approach, we determined differing phenotypic effects associated with the different components of aerosol. The particle phase of diluted combustion aerosols was found to induce increased cell death in macrophages, while the gas phase was found more to affect the metabolic profile. In particular, a higher cytotoxicity of DF aerosol emission was observed in relation to the HFO aerosol. Furthermore, macrophage exposure to the gas phase of HFO leads to an induction of a pro-inflammatory metabolic and proteomic phenotype. These results validate the effects found in lung epithelial cells, confirming the role of inflammation and cellular stress in the respon

Published
2016

32. Metabolic Profiling as Well as Stable Isotope Assisted Metabolic and Proteomic Analysis of RAW 264.7 Macrophages Exposed to Ship Engine Aerosol Emissions: Different Effects of Heavy Fuel Oil and Refined Diesel Fuel

Author

Sapcariu, Sean C., primary, Kanashova, Tamara, additional, Dilger, Marco, additional, Diabaté, Silvia, additional, Oeder, Sebastian, additional, Passig, Johannes, additional, Radischat, Christian, additional, Buters, Jeroen, additional, Sippula, Olli, additional, Streibel, Thorsten, additional, Paur, Hanns-Rudolf, additional, Schlager, Christoph, additional, Mülhopt, Sonja, additional, Stengel, Benjamin, additional, Rabe, Rom, additional, Harndorf, Horst, additional, Krebs, Tobias, additional, Karg, Erwin, additional, Gröger, Thomas, additional, Weiss, Carsten, additional, Dittmar, Gunnar, additional, Hiller, Karsten, additional, and Zimmermann, Ralf, additional

Published
2016
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33. Particulate Matter from Both Heavy Fuel Oil and Diesel Fuel Shipping Emissions Show Strong Biological Effects on Human Lung Cells at Realistic and Comparable In Vitro Exposure Conditions

Author

HICE [sponsor], Sapcariu, Sean, Oeder, Sebastian, Kanashova, Tamara, Sippula, Olli, Streibel, Thorsten, Arteaga-Salas, Jose Manuel, Passig, Johannes, Dilger, Marco, Paur, Hanns-Rudolf, Schlager, Christoph, Mülhopt, Sonja, Diabaté, Silvia, Weiss, Carsten, Stengel, Benjamin, Rabe, Rom, Harnsdorf, Horst, Torvela, Tiina, Jokiniemi, Jorma, Hirvonen, Maija-Riitta, Schmidt-Weber, Carsten, Traidl-Hoffmann, Claudia, BéruBé, Kelly, Wlodarczyk, Anna, Prytherch, Zoe, Michalke, Bernhard, Krebs, Tobias, Prévot, Andre, Kelbg, Michael, Tiggesbäumker, Josef, Karg, Erwin, Jaokobi, Gert, Scholtes, Sorana, Schnelle-Kreis, Jürgen, Lintelmann, Jutta, Matuschek, Georg, Sklorz, Martin, Klingbeil, Sophie, Orasche, Jürgen, Richthammer, Patrick, Müller, Laarnie, Elsasser, Michael, Reda, Ahmed, Gröger, Thomas, Weggler, Benedikt, Schwemer, Theo, Czech, Hendryk, Rüger, Christopher, Abbaszade, Gülcin, Radischat, Christian, Hiller, Karsten, Buters, Jeroen, Dittmar, Gunnar, Zimmermann, Ralf, HICE [sponsor], Sapcariu, Sean, Oeder, Sebastian, Kanashova, Tamara, Sippula, Olli, Streibel, Thorsten, Arteaga-Salas, Jose Manuel, Passig, Johannes, Dilger, Marco, Paur, Hanns-Rudolf, Schlager, Christoph, Mülhopt, Sonja, Diabaté, Silvia, Weiss, Carsten, Stengel, Benjamin, Rabe, Rom, Harnsdorf, Horst, Torvela, Tiina, Jokiniemi, Jorma, Hirvonen, Maija-Riitta, Schmidt-Weber, Carsten, Traidl-Hoffmann, Claudia, BéruBé, Kelly, Wlodarczyk, Anna, Prytherch, Zoe, Michalke, Bernhard, Krebs, Tobias, Prévot, Andre, Kelbg, Michael, Tiggesbäumker, Josef, Karg, Erwin, Jaokobi, Gert, Scholtes, Sorana, Schnelle-Kreis, Jürgen, Lintelmann, Jutta, Matuschek, Georg, Sklorz, Martin, Klingbeil, Sophie, Orasche, Jürgen, Richthammer, Patrick, Müller, Laarnie, Elsasser, Michael, Reda, Ahmed, Gröger, Thomas, Weggler, Benedikt, Schwemer, Theo, Czech, Hendryk, Rüger, Christopher, Abbaszade, Gülcin, Radischat, Christian, Hiller, Karsten, Buters, Jeroen, Dittmar, Gunnar, and Zimmermann, Ralf

Published
2015

34. Isolation of native plasma membrane H+‐ATPase (Pma1p) in both the active and basal activation states.

Author

Pedersen, Jesper Torbøl, Kanashova, Tamara, Dittmar, Gunnar, and Palmgren, Michael

Subjects
CELL membranes, ADENOSINE triphosphatase, POLYMERSOMES, PROTEIN hydrolysates, SACCHAROMYCES cerevisiae
Abstract

The yeast plasma membrane H+‐ATPase Pma1p is a P‐type ATPase that energizes the yeast plasma membrane. Pma1p exists in two activation states: an autoinhibited basal state and an activated state. Here we show that functional and stable Pma1p can be purified in native form and reconstituted in artificial liposomes without altering its activation state. Acetylated tubulin has previously been reported to maintain Pma1p in the basal state but, as this protein was absent from the purified preparations, it cannot be an essential component of the autoinhibitory mechanism. Purification of and reconstitution of native Pma1p in both activation states opens up for a direct comparison of the transport properties of these states, which allowed us to confirm that the basal state has a low coupling ratio between ATP hydrolysis and protons pumped, whereas the activated state has a high coupling ratio. The ability to prepare native Pma1p in both activation states will facilitate further structural and biochemical studies examining the mechanism by which plasma membrane H+‐ATPases are autoinhibited. [ABSTRACT FROM AUTHOR]

Published
2018
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36. Simultaneous extraction of proteins and metabolites from cells in culture

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Metabolomics (Hiller Group) [research center], Sapcariu, Sean, Kanashova, Tamara, Weindl, Daniel, Ghelfi, Jenny, Dittmar, Gunnar, Hiller, Karsten, Luxembourg Centre for Systems Biomedicine (LCSB): Metabolomics (Hiller Group) [research center], Sapcariu, Sean, Kanashova, Tamara, Weindl, Daniel, Ghelfi, Jenny, Dittmar, Gunnar, and Hiller, Karsten

Published
2014
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37. Muscle RING-finger 2 and 3 maintain striated-muscle structure and function.

Author

Lodka, Dörte, Pahuja, Aanchal, Geers ‐ Knörr, Cornelia, Scheibe, Renate J., Nowak, Marcel, Hamati, Jida, Köhncke, Clemens, Purfürst, Bettina, Kanashova, Tamara, Schmidt, Sibylle, Glass, David J., Morano, Ingo, Heuser, Arnd, Kraft, Theresia, Bassel ‐ Duby, Rhonda, Olson, Eric N., Dittmar, Gunnar, Sommer, Thomas, and Fielitz, Jens

Subjects
FINGERS, STRIATED muscle, UBIQUITIN ligases, BIOLOGICAL adaptation, CELL culture
Abstract

Background The Muscle-specific RING-finger (MuRF) protein family of E3 ubiquitin ligases is important for maintenance of muscular structure and function. MuRF proteins mediate adaptation of striated muscles to stress. MuRF2 and MuRF3 bind to microtubules and are implicated in sarcomere formation with noticeable functional redundancy. However, if this redundancy is important for muscle function in vivo is unknown. Our objective was to investigate cooperative function of MuRF2 and MuRF3 in the skeletal muscle and the heart in vivo. Methods MuRF2 and MuRF3 double knockout mice (DKO) were generated and phenotypically characterized. Skeletal muscle and the heart were investigated by morphological measurements, histological analyses, electron microscopy, immunoblotting, and real-time PCR. Isolated muscles were subjected to in vitro force measurements. Cardiac function was determined by echocardiography and working heart preparations. Function of cardiomyocytes was measured in vitro. Cell culture experiments and mass-spectrometry were used for mechanistic analyses. Results DKO mice showed a protein aggregate myopathy in skeletal muscle. Maximal force development was reduced in DKO soleus and extensor digitorum longus. Additionally, a fibre type shift towards slow/type I fibres occurred in DKO soleus and extensor digitorum longus. MuRF2 and MuRF3-deficient hearts showed decreased systolic and diastolic function. Further analyses revealed an increased expression of the myosin heavy chain isoform beta/slow and disturbed calcium handling as potential causes for the phenotype in DKO hearts. Conclusions The redundant function of MuRF2 and MuRF3 is important for maintenance of skeletal muscle and cardiac structure and function in vivo. [ABSTRACT FROM AUTHOR]

Published
2016
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38. Additional file 6 of Influence of wood species on toxicity of log-wood stove combustion aerosols: a parallel animal and air-liquid interface cell exposure study on spruce and pine smoke

Author

Ihantola, Tuukka, Bucchianico, Sebastiano Di, Happo, Mikko, Ihalainen, Mika, Uski, Oskari, Bauer, Stefanie, Kuuspalo, Kari, Sippula, Olli, Tissari, Jarkko, Oeder, Sebastian, Hartikainen, Anni, Rönkkö, Teemu J., Maria-Viola Martikainen, Huttunen, Kati, Vartiainen, Petra, Suhonen, Heikki, Kortelainen, Miika, Lamberg, Heikki, Leskinen, Ari, Sklorz, Martin, Michalke, Bernhard, Dilger, Marco, Weiss, Carsten, Dittmar, Gunnar, Beckers, Johannes, Irmler, Martin, Buters, Jeroen, Candeias, Joana, Hendryk Czech, Yli-Pirilä, Pasi, Gülcin Abbaszade, Jakobi, Gert, Orasche, Jürgen, Schnelle-Kreis, Jürgen, Kanashova, Tamara, Karg, Erwin, Streibel, Thorsten, Passig, Johannes, Hakkarainen, Henri, Jokiniemi, Jorma, Zimmermann, Ralf, Maija-Riitta Hirvonen, and Jalava, Pasi I.

Subjects
13. Climate action
Abstract

Additional file 6 Table S2. All measured organic compounds from wood combustion emissions. Organic compounds were sampled over 4-h exposure. Concentrations are calculated as averages from three test cycles ± standard deviation.

39. Additional file 1 of Influence of wood species on toxicity of log-wood stove combustion aerosols: a parallel animal and air-liquid interface cell exposure study on spruce and pine smoke

Author

Ihantola, Tuukka, Bucchianico, Sebastiano Di, Happo, Mikko, Ihalainen, Mika, Uski, Oskari, Bauer, Stefanie, Kuuspalo, Kari, Sippula, Olli, Tissari, Jarkko, Oeder, Sebastian, Hartikainen, Anni, Rönkkö, Teemu J., Maria-Viola Martikainen, Huttunen, Kati, Vartiainen, Petra, Suhonen, Heikki, Kortelainen, Miika, Lamberg, Heikki, Leskinen, Ari, Sklorz, Martin, Michalke, Bernhard, Dilger, Marco, Weiss, Carsten, Dittmar, Gunnar, Beckers, Johannes, Irmler, Martin, Buters, Jeroen, Candeias, Joana, Hendryk Czech, Yli-Pirilä, Pasi, Gülcin Abbaszade, Jakobi, Gert, Orasche, Jürgen, Schnelle-Kreis, Jürgen, Kanashova, Tamara, Karg, Erwin, Streibel, Thorsten, Passig, Johannes, Hakkarainen, Henri, Jokiniemi, Jorma, Zimmermann, Ralf, Maija-Riitta Hirvonen, and Jalava, Pasi I.

Subjects
13. Climate action
Abstract

Additional file 1: Table S1. Calibration and quantification mixtures of isotope labelled internal standards and calibration standards.

40. Additional file 6 of Influence of wood species on toxicity of log-wood stove combustion aerosols: a parallel animal and air-liquid interface cell exposure study on spruce and pine smoke

Author

Ihantola, Tuukka, Bucchianico, Sebastiano Di, Happo, Mikko, Ihalainen, Mika, Uski, Oskari, Bauer, Stefanie, Kuuspalo, Kari, Sippula, Olli, Tissari, Jarkko, Oeder, Sebastian, Hartikainen, Anni, Rönkkö, Teemu J., Maria-Viola Martikainen, Huttunen, Kati, Vartiainen, Petra, Suhonen, Heikki, Kortelainen, Miika, Lamberg, Heikki, Leskinen, Ari, Sklorz, Martin, Michalke, Bernhard, Dilger, Marco, Weiss, Carsten, Dittmar, Gunnar, Beckers, Johannes, Irmler, Martin, Buters, Jeroen, Candeias, Joana, Hendryk Czech, Yli-Pirilä, Pasi, Gülcin Abbaszade, Jakobi, Gert, Orasche, Jürgen, Schnelle-Kreis, Jürgen, Kanashova, Tamara, Karg, Erwin, Streibel, Thorsten, Passig, Johannes, Hakkarainen, Henri, Jokiniemi, Jorma, Zimmermann, Ralf, Maija-Riitta Hirvonen, and Jalava, Pasi I.

Subjects
13. Climate action
Abstract

Additional file 6 Table S2. All measured organic compounds from wood combustion emissions. Organic compounds were sampled over 4-h exposure. Concentrations are calculated as averages from three test cycles ± standard deviation.

41. Particulate Matter from Both Heavy Fuel Oil and Diesel Fuel Shipping Emissions Show Strong Biological Effects on Human Lung Cells at Realistic and Comparable In Vitro Exposure Conditions

Author

Oeder, Sebastian, Kanashova, Tamara, Sippula, Olli, Sapcariu, Sean C., Streibel, Thorsten, Arteaga-Salas, Jose M., Passig, Johannes, Dilger, Marco, Paur, Hanns-Rudolf, Schlager, Christoph, Mulhopt, Sonja, Diabate, Silvia, Weiss, Carsten, Stengel, Benjamin, Rabe, Rom, Harndorf, Horst, Torvela, Tiina, Jokiniemi, Jorma K., Hirvonen, Maija-Riitta, Schmidt-Weber, Carsten, Traidl-Hoffmann, Claudia, BéruBé, Kelly A., Wlodarczyk, Anna J., Prytherch, Zoe, Michalke, Bernhard, Krebs, Tobias, Prévôt, André S.H., Kelbg, Michael, Tiggesbäumker, Josef, Karg, Erwin, Jakobi, Gert, Scholtes, Sorana, Schnelle-Kreis, Jürgen, Lintelmann, Jutta, Matuschek, Georg, Sklorz, Martin, Klingbeil, Sophie, Orasche, Jürgen, Richthammer, Patrick, Müller, Laarnie, Elsasser, Michael, Reda, Ahmed, Gröger, Thomas, Weggler, Benedikt, Schwemer, Theo, Czech, Hendryk, Rüger, Christopher P., Abbaszade, Gülcin, Radischat, Christian, Hiller, Karsten, Buters, Jeroen T.M., Dittmar, Gunnar, and Zimmermann, Ralf

Subjects
13. Climate action, complex mixtures, 3. Good health
Abstract

Background Ship engine emissions are important with regard to lung and cardiovascular diseases especially in coastal regions worldwide. Known cellular responses to combustion particles include oxidative stress and inflammatory signalling. Objectives To provide a molecular link between the chemical and physical characteristics of ship emission particles and the cellular responses they elicit and to identify potentially harmful fractions in shipping emission aerosols. Methods Through an air-liquid interface exposure system, we exposed human lung cells under realistic in vitro conditions to exhaust fumes from a ship engine running on either common heavy fuel oil (HFO) or cleaner-burning diesel fuel (DF). Advanced chemical analyses of the exhaust aerosols were combined with transcriptional, proteomic and metabolomic profiling including isotope labelling methods to characterise the lung cell responses. Results The HFO emissions contained high concentrations of toxic compounds such as metals and polycyclic aromatic hydrocarbon, and were higher in particle mass. These compounds were lower in DF emissions, which in turn had higher concentrations of elemental carbon (“soot”). Common cellular reactions included cellular stress responses and endocytosis. Reactions to HFO emissions were dominated by oxidative stress and inflammatory responses, whereas DF emissions induced generally a broader biological response than HFO emissions and affected essential cellular pathways such as energy metabolism, protein synthesis, and chromatin modification. Conclusions Despite a lower content of known toxic compounds, combustion particles from the clean shipping fuel DF influenced several essential pathways of lung cell metabolism more strongly than particles from the unrefined fuel HFO. This might be attributable to a higher soot content in DF. Thus the role of diesel soot, which is a known carcinogen in acute air pollution-induced health effects should be further investigated. For the use of HFO and DF we recommend a reduction of carbonaceous soot in the ship emissions by implementation of filtration devices., PLoS ONE, 10 (6), ISSN:1932-6203

42. Additional file 3 of Influence of wood species on toxicity of log-wood stove combustion aerosols: a parallel animal and air-liquid interface cell exposure study on spruce and pine smoke

Author

Ihantola, Tuukka, Bucchianico, Sebastiano Di, Happo, Mikko, Ihalainen, Mika, Uski, Oskari, Bauer, Stefanie, Kuuspalo, Kari, Sippula, Olli, Tissari, Jarkko, Oeder, Sebastian, Hartikainen, Anni, Rönkkö, Teemu J., Maria-Viola Martikainen, Huttunen, Kati, Vartiainen, Petra, Suhonen, Heikki, Kortelainen, Miika, Lamberg, Heikki, Leskinen, Ari, Sklorz, Martin, Michalke, Bernhard, Dilger, Marco, Weiss, Carsten, Dittmar, Gunnar, Beckers, Johannes, Irmler, Martin, Buters, Jeroen, Candeias, Joana, Hendryk Czech, Yli-Pirilä, Pasi, Gülcin Abbaszade, Jakobi, Gert, Orasche, Jürgen, Schnelle-Kreis, Jürgen, Kanashova, Tamara, Karg, Erwin, Streibel, Thorsten, Passig, Johannes, Hakkarainen, Henri, Jokiniemi, Jorma, Zimmermann, Ralf, Maija-Riitta Hirvonen, and Jalava, Pasi I.

Subjects
13. Climate action, fungi
Abstract

Additional file 3 Figure S1. Physical properties in the diluted exposure exhaust per day to day, for spruce (A) and pine (B) experiments. Parts A and C show average of 3 experiment days total suspended particulate mass (TSP), lung deposited surface area (LDSA) and particle number concentration (PNC) during exposures.

43. Additional file 1 of Influence of wood species on toxicity of log-wood stove combustion aerosols: a parallel animal and air-liquid interface cell exposure study on spruce and pine smoke

Author

Ihantola, Tuukka, Bucchianico, Sebastiano Di, Happo, Mikko, Ihalainen, Mika, Uski, Oskari, Bauer, Stefanie, Kuuspalo, Kari, Sippula, Olli, Tissari, Jarkko, Oeder, Sebastian, Hartikainen, Anni, Rönkkö, Teemu J., Maria-Viola Martikainen, Huttunen, Kati, Vartiainen, Petra, Suhonen, Heikki, Kortelainen, Miika, Lamberg, Heikki, Leskinen, Ari, Sklorz, Martin, Michalke, Bernhard, Dilger, Marco, Weiss, Carsten, Dittmar, Gunnar, Beckers, Johannes, Irmler, Martin, Buters, Jeroen, Candeias, Joana, Hendryk Czech, Yli-Pirilä, Pasi, Gülcin Abbaszade, Jakobi, Gert, Orasche, Jürgen, Schnelle-Kreis, Jürgen, Kanashova, Tamara, Karg, Erwin, Streibel, Thorsten, Passig, Johannes, Hakkarainen, Henri, Jokiniemi, Jorma, Zimmermann, Ralf, Maija-Riitta Hirvonen, and Jalava, Pasi I.

Subjects
13. Climate action
Abstract

Additional file 1: Table S1. Calibration and quantification mixtures of isotope labelled internal standards and calibration standards.

44. Additional file 3 of Influence of wood species on toxicity of log-wood stove combustion aerosols: a parallel animal and air-liquid interface cell exposure study on spruce and pine smoke

Author

Ihantola, Tuukka, Bucchianico, Sebastiano Di, Happo, Mikko, Ihalainen, Mika, Uski, Oskari, Bauer, Stefanie, Kuuspalo, Kari, Sippula, Olli, Tissari, Jarkko, Oeder, Sebastian, Hartikainen, Anni, Rönkkö, Teemu J., Maria-Viola Martikainen, Huttunen, Kati, Vartiainen, Petra, Suhonen, Heikki, Kortelainen, Miika, Lamberg, Heikki, Leskinen, Ari, Sklorz, Martin, Michalke, Bernhard, Dilger, Marco, Weiss, Carsten, Dittmar, Gunnar, Beckers, Johannes, Irmler, Martin, Buters, Jeroen, Candeias, Joana, Hendryk Czech, Yli-Pirilä, Pasi, Gülcin Abbaszade, Jakobi, Gert, Orasche, Jürgen, Schnelle-Kreis, Jürgen, Kanashova, Tamara, Karg, Erwin, Streibel, Thorsten, Passig, Johannes, Hakkarainen, Henri, Jokiniemi, Jorma, Zimmermann, Ralf, Maija-Riitta Hirvonen, and Jalava, Pasi I.

Subjects
13. Climate action, fungi
Abstract

Additional file 3 Figure S1. Physical properties in the diluted exposure exhaust per day to day, for spruce (A) and pine (B) experiments. Parts A and C show average of 3 experiment days total suspended particulate mass (TSP), lung deposited surface area (LDSA) and particle number concentration (PNC) during exposures.

45. Metabolic Profiling as Well as Stable Isotope Assisted Metabolic and Proteomic Analysis of RAW 264.7 Macrophages Exposed to Ship Engine Aerosol Emissions: Different Effects of Heavy Fuel Oil and Refined Diesel Fuel

Author

Sapcariu, Sean C., Kanashova, Tamara, Dilger, Marco, Diabat��, Silvia, Oeder, Sebastian, Passig, Johannes, Radischat, Christian, Buters, Jeroen, Sippula, Olli, Streibel, Thorsten, Paur, Hanns-Rudolf, Schlager, Christoph, M��lhopt, Sonja, Stengel, Benjamin, Rabe, Rom, Harndorf, Horst, Krebs, Tobias, Karg, Erwin, Gr��ger, Thomas, Weiss, Carsten, Dittmar, Gunnar, Hiller, Karsten, and Zimmermann, Ralf

Subjects
13. Climate action
Abstract

Exposure to air pollution resulting from fossil fuel combustion has been linked to multiple short-term and long term health effects. In a previous study, exposure of lung epithelial cells to engine exhaust from heavy fuel oil (HFO) and diesel fuel (DF), two of the main fuels used in marine engines, led to an increased regulation of several pathways associated with adverse cellular effects, including pro-inflammatory pathways. In addition, DF exhaust exposure was shown to have a wider response on multiple cellular regulatory levels compared to HFO emissions, suggesting a potentially higher toxicity of DF emissions over HFO. In order to further understand these effects, as well as to validate these findings in another cell line, we investigated macrophages under the same conditions as a more inflammationrelevant model. An air-liquid interface aerosol exposure system was used to provide a more biologically relevant exposure system compared to submerged experiments, with cells exposed to either the complete aerosol (particle and gas phase), or the gas phase only (with particles filtered out). Data from cytotoxicity assays were integrated with metabolomics and proteomics analyses, including stable isotope-assisted metabolomics, in order to uncover pathways affected by combustion aerosol exposure in macrophages. Through this approach, we determined differing phenotypic effects associated with the different components of aerosol. The particle phase of diluted combustion aerosols was found to induce increased cell death in macrophages, while the gas phase was found more to affect the metabolic profile. In particular, a higher cytotoxicity of DF aerosol emission was observed in relation to the HFO aerosol. Furthermore, macrophage exposure to the gas phase of HFO leads to an induction of a pro-inflammatory metabolic and proteomic phenotype. These results validate the effects found in lung epithelial cells, confirming the role of inflammation and cellular stress in the response to combustion aerosols.

46. The arginine methyltransferase PRMT7 promotes extravasation of monocytes resulting in tissue injury in COPD

Author

Gizem Günes Günsel, Thomas M. Conlon, Aicha Jeridi, Rinho Kim, Zeynep Ertüz, Niklas J. Lang, Meshal Ansari, Mariia Novikova, Dongsheng Jiang, Maximilian Strunz, Mariia Gaianova, Christine Hollauer, Christina Gabriel, Ilias Angelidis, Sebastian Doll, Jeanine C. Pestoni, Stephanie L. Edelmann, Marlene Sophia Kohlhepp, Adrien Guillot, Kevin Bassler, Hannelore P. Van Eeckhoutte, Özgecan Kayalar, Nur Konyalilar, Tamara Kanashova, Sophie Rodius, Carolina Ballester-López, Carlos M. Genes Robles, Natalia Smirnova, Markus Rehberg, Charu Agarwal, Ioanna Krikki, Benoit Piavaux, Stijn E. Verleden, Bart Vanaudenaerde, Melanie Königshoff, Gunnar Dittmar, Ken R. Bracke, Joachim L. Schultze, Henrik Watz, Oliver Eickelberg, Tobias Stoeger, Gerald Burgstaller, Frank Tacke, Vigo Heissmeyer, Yuval Rinkevich, Hasan Bayram, Herbert B. Schiller, Marcus Conrad, Robert Schneider, Ali Önder Yildirim, Kayalar, Özgecan, Konyalılar, Nur, Bayram, Hasan (ORCID 0000-0002-5236-766X & YÖK ID 4890), Yıldırım, Ali Önder, Günsel, Gizem Güneş, Conlon, Thomas M., Jeridi, Aicha, Kim, Rinho, Ertuez, Zeynep, Lang, Niklas J., Ansari, Meshal, Novikova, Mariia, Jiang, Dongsheng, Strunz, Maximilian, Gaianova, Mariia, Hollauer, Christine, Gabriel, Christina, Angelidis, Ilias, Doll, Sebastian, Pestoni, Jeanine C., Edelmann, Stephanie L., Kohlhepp, Marlene Sophia, Guillot, Adrien, Bassler, Kevin, Van Eeckhoutte, Hannelore P., Kanashova, Tamara, Rodius, Sophie, Ballester-Lopez, Carolina, Robles, Carlos M. Genes, Smirnova, Natalia, Rehberg, Markus, Agarwal, Charu, Krikki, Ioanna, Piavaux, Benoit, Verleden, Stijn E., Vanaudenaerde, Bart, Koenigshoff, Melanie, Dittmar, Gunnar, Bracke, Ken R., Schultze, Joachim L., Watz, Henrik, Eickelberg, Oliver, Stoeger, Tobias, Burgstaller, Gerald, Tacke, Frank, Heissmeyer, Vigo, Rinkevich, Yuval, Schiller, Herbert B., Conrad, Marcus, Schneider, Robert, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), and School of Medicine

Subjects
EXPRESSION, Protein-Arginine N-Methyltransferases, metabolism [Histones], metabolism [Arginine], PRMT7 protein, human, General Physics and Astronomy, KAPPA-B, PRMT2 protein, human, Arginine, Animals, Histones, Humans, Intracellular signaling peptides and proteins, Mice, Monocytes, Protein-arginine n-methyltransferases, Pulmonary disease, Chronic obstructive, General Biochemistry, Genetics and Molecular Biology, Multidisciplinary sciences, Pulmonary Disease, Chronic Obstructive, INFLAMMATION, PRMT7 protein, mouse, SMOKE-INDUCED EMPHYSEMA, Medicine and Health Sciences, PHOSPHORYLATION, metabolism [Protein-Arginine N-Methyltransferases], RAP1, Multidisciplinary, METHYLATION, Intracellular Signaling Peptides and Proteins, Biology and Life Sciences, General Chemistry, DIFFERENTIATION, CELLS, genetics [Pulmonary Disease, Chronic Obstructive], ddc:500, Human medicine, Technology Platforms, ELASTASE, metabolism [Monocytes]
Abstract

Extravasation of monocytes into tissue and to the site of injury is a fundamental immunological process, which requires rapid responses via post translational modifications (PTM) of proteins. Protein arginine methyltransferase 7 (PRMT7) is an epigenetic factor that has the capacity to mono-methylate histones on arginine residues. Here we show that in chronic obstructive pulmonary disease (COPD) patients, PRMT7 expression is elevated in the lung tissue and localized to the macrophages. In mouse models of COPD, lung fibrosis and skin injury, reduced expression of PRMT7 associates with decreased recruitment of monocytes to the site of injury and hence less severe symptoms. Mechanistically, activation of NF-kappa B/RelA in monocytes induces PRMT7 transcription and consequential mono-methylation of histones at the regulatory elements of RAP1A, which leads to increased transcription of this gene that is responsible for adhesion and migration of monocytes. Persistent monocyte-derived macrophage accumulation leads to ALOX5 over-expression and accumulation of its metabolite LTB4, which triggers expression of ACSL4 a ferroptosis promoting gene in lung epithelial cells. Conclusively, inhibition of arginine mono-methylation might offer targeted intervention in monocyte-driven inflammatory conditions that lead to extensive tissue damage if left untreated. Chronic obstructive pulmonary disease is a progressive and incurable chronic condition that involves accumulation of inflammatory macrophages in the lung tissue. Authors here show in mouse models of lung disease that PRMT7, a protein arginine methyltransferase, is an important regulator of recruitment and the pro-inflammatory phenotype of macrophages., German Center for Lung Research (DZL); German Research Foundation; Deutsche Forschungsgemeinschaft (DFG); DFG Priority Program 2306; German Bundesministerium für Bildung und Forschung (BMBF) VIP + program NeuroProtect; Ministry of Science and Higher Education of the Russian Federation; Else Kröner-Fresenius-Stiftung; European Union (EU); Horizon 2020; European Research Council (ERC); Research and Innovation Program; Projekt DEAL

Published
2022

47. Isolation of native plasma membrane H + -ATPase (Pma1p) in both the active and basal activation states.

Author

Pedersen JT, Kanashova T, Dittmar G, and Palmgren M

Abstract

The yeast plasma membrane H + -ATPase Pma1p is a P-type ATPase that energizes the yeast plasma membrane. Pma1p exists in two activation states: an autoinhibited basal state and an activated state. Here we show that functional and stable Pma1p can be purified in native form and reconstituted in artificial liposomes without altering its activation state. Acetylated tubulin has previously been reported to maintain Pma1p in the basal state but, as this protein was absent from the purified preparations, it cannot be an essential component of the autoinhibitory mechanism. Purification of and reconstitution of native Pma1p in both activation states opens up for a direct comparison of the transport properties of these states, which allowed us to confirm that the basal state has a low coupling ratio between ATP hydrolysis and protons pumped, whereas the activated state has a high coupling ratio. The ability to prepare native Pma1p in both activation states will facilitate further structural and biochemical studies examining the mechanism by which plasma membrane H + -ATPases are autoinhibited.

Published
2018
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