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2. Burr-hole drainage with or without irrigation for chronic subdural haematoma (FINISH): a Finnish, nationwide, parallel-group, multicentre, randomised, controlled, non-inferiority trial

Author

Ahmed, Abdirisak, Areda, Tarmo, Bartek, Jiri Jr, Czuba, Tomasz, Danner, Nils, Elomaa, Antti-Pekka, Frantzén, Janek, Haapala, Ilkka, Haapasalo, Joonas, Heikkilä, Juuso, Hellman, Minttu, Henttonen, Henna, Huuska, Nora, Järvinen, Teppo LN, Jyrkkänen, Henna-Kaisa, Kaipainen, Aku, Kämäräinen, Olli-Pekka, Kämppi, Hanna, Kelahaara, Milla, Kivisaari, Riku, Klimko, Nikolai, Knuutinen, Oula A, Koivisto, Timo, Korhonen, Tommi, Koskimäki, Janne, Kovalainen, Anselmi, Kuparinen, Xenia, Laukka, Dan, Lehecka, Martin, Lehtimäki, Kai, Leinonen, Ville, Lönnrot, Kimmo, Luikku, Antti, Luostarinen, Teemu, Luoto, Teemu, Luotonen, Janne, Lustig-Tammi, Lauriina, Maanpää, Henna-Riikka, Määttä, Jenni, Möttönen, Timo, Netti, Eliisa, Nevaharju-Sarantis, Laura, Niemelä, Mika, Niskakangas, Tero, Nissinen, Mette, Nurminen, Ville, Oinas, Minna, Ollonen, Teemu, Östberg, Anna, Oulasvirta, Elias, Pantzar, Krista, Piilonen, Katri, Pohjola, Anni, Polvivaara, Markus, Posti, Jussi P, Raj, Rahul, Rajala, Linnea, Ranstam, Jonas, Rauhala, Minna, Rezai Jahromi, Behnam, Roiha, Miika, Saarenpää, Ilkka, Sajanti, Antti, Salmi, Henrikki, Satopää, Jarno, Schwartz, Christoph, Shemeikka, Niina, Sorto, Pia, Taimela, Simo, Tetri, Sami, Thesleff, Tuomo, Tommiska, Pihla, Tuomisto, Maarit, Vartiainen, Nuutti, Vasankari, Ville, Virta, Jyri, Visuri, Mikko, Walle, Paula, Zeiler, Frederick A, Korhonen, Tommi K, and Järvinen, Teppo L N

Published
2024
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6. Association between postoperative thromboembolic and hemorrhagic complications and clinical outcomes after surgery for chronic subdural hematoma in patients with anticoagulation therapy for atrial fibrillation.

Author

Tommiska, Pihla, Knuutinen, Oula, Lönnrot, Kimmo, Kivisaari, Riku, Raj, Rahul, Ahmed, Abdirisak, Areda, Tarmo, Bartek Jr, Jiri, Czuba, Tomasz, Danner, Nils, Elomaa, Antti-Pekka, Frantzén, Janek, Haapala, Ilkka, Haapasalo, Joonas, Heikkilä, Juuso, Hellman, Minttu, Henttonen, Henna, Huuska, Nora, Järvinen, Teppo LN, and Jyrkkänen, Henna-Kaisa

Subjects
SUBDURAL hematoma, MEDICAL sciences, ATRIAL fibrillation, TREATMENT effectiveness, THROMBOEMBOLISM
Abstract

Purpose: A substantial proportion of patients undergoing surgery for chronic subdural hematoma (CSDH) use anticoagulation medication due to atrial fibrillation (AF). We assessed the risk of postoperative thromboembolic and hemorrhagic complications in CSDH surgery patients with a history of anticoagulation for AF and their association with outcome. Methods: This posthoc analysis of a nationwide multicenter randomized controlled trial conducted during 2020–2022 included CSDH patients undergoing surgery with a history of preoperative anticoagulation use for AF. We assessed the incidence of thromboembolic and hemorrhagic complications and their associations with functional outcomes and mortality. Results: Of 589 patients, 128 patients (median age 83 years, 24% females) were on anticoagulation medication due to AF. The incidences of postoperative thromboembolic and hemorrhagic complications were 8% and 6%, respectively. A significantly higher proportion of patients with a thromboembolic complication had unfavorable functional outcome (70% vs. 21%, p < 0.001) and higher mortality (50% vs. 14%) than those without. After adjusting for risk factors, a thromboembolic complication was independently associated with a higher risk for unfavorable outcome (OR 16.8, 95% CI 3.0–94.2) and death (OR 11.1, 95% CI 2.4–52.0). Similarly, hemorrhagic complications associated independently with unfavorable outcome, although the effect size was smaller than for thromboembolic complications. Conclusion: The risk for thromboembolic complications seemed to be slightly higher than the risk for postoperative hemorrhagic complications after CSDH surgery in patients with a history of preoperative anticoagulation medication use due to AF. The occurrence of a thromboembolic complication was detrimental for patient prognosis, underscoring the importance of strategies to prevent thromboembolic events. There is an urgent need for a trial assessing the optimal timing of restarting anticoagulation medication after CSDH surgery. Trial registration: ClinicalTrials.gov identifier NCT04203550. [ABSTRACT FROM AUTHOR]

Published
2025
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7. Night-time versus daytime surgical outcomes in chronic subdural hematomas: a post hoc analysis of the FINISH randomized trial.

Author

Oulasvirta, Elias, Knuutinen, Oula, Tommiska, Pihla, Kivisaari, Riku, Raj, Rahul, Ahmed, Abdirisak, Areda, Tarmo, Bartek Jr, Jiri, Czuba, Tomasz, Danner, Nils, Elomaa, Antti-Pekka, Frantzén, Janek, Haapala, Ilkka, Haapasalo, Joonas, Heikkilä, Juuso, Hellman, Minttu, Henttonen, Henna, Huuska, Nora, Järvinen, Teppo LN, and Jyrkkänen, Henna-Kaisa

Subjects
LOGISTIC regression analysis, INTRACRANIAL hemorrhage, SUBDURAL hematoma, TREATMENT effectiveness, MEDICAL drainage
Abstract

Objective: The optimal timing of surgical intervention for chronic subdural hematomas (CSDH), specifically night-time versus daytime, remains a subject of debate, with concerns about the potential impact of circadian timing on surgical outcomes. This study evaluated the association between the timing of burr-hole drainage for CSDH and postoperative outcomes, comparing night-time and daytime surgeries. Methods: In a post-hoc analysis of the FINISH trial, we included adult patients with symptomatic unilateral or bilateral CSDH who underwent burr-hole drainage between January 2020 and August 2022. Night-time surgery was defined as procedures starting between 23:00 and 06:00, with daytime surgeries occurring between 06:01 and 22:59. The primary outcome was functional outcome at six months post-surgery, assessed using the modified Rankin Scale (mRS), with favorable outcomes defined as an mRS of 0–3. Secondary outcomes included mortality, reoperation rates, and adverse events within six months. Results: Our analysis of 589 patients (83% daytime surgery, 17% night-time surgery) revealed no significant differences in baseline characteristics. The unadjusted analysis suggested a higher rate of favorable functional outcomes in the night-time surgery group than in the daytime group (94% vs. 86%, p = 0.037). Mortality, adverse events, and reoperation rates were similar in the groups. Adjusted logistic regression analyses, accounting for potential confounders, indicated that night-time surgery was not associated with a higher risk of unfavorable functional outcomes compared to daytime surgery. Conclusions: Our findings suggest that night-time surgery versus daytime surgery is not associated with worse postoperative outcomes. These findings challenges the traditional preference for daytime CSDH surgery and emphasizes the potential for flexibility in surgical scheduling to optimize patient care in CSDH management. [ABSTRACT FROM AUTHOR]

Published
2024
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8. In vivo assessment of Lewy body and beta-amyloid copathologies in idiopathic normal pressure hydrocephalus: prevalence and associations with clinical features and surgery outcome

Author

Giannini, Giulia, Baiardi, Simone, Dellavalle, Sofia, Zenesini, Corrado, Cevoli, Sabina, Danner, Nils, Jyrkkänen, Henna-Kaisa, Rossi, Marcello, Polischi, Barbara, Quadalti, Corinne, Stefanini, Camilla, Cortelli, Pietro, Milletti, David, Herukka, Sanna-Kaisa, Palandri, Giorgio, Leinonen, Ville, and Parchi, Piero

Published
2022
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9. Burr-hole drainage with or without irrigation for chronic subdural haematoma (FINISH): a Finnish, nationwide, parallel-group, multicentre, randomised, controlled, non-inferiority trial

Author

Raj, Rahul, primary, Tommiska, Pihla, additional, Koivisto, Timo, additional, Leinonen, Ville, additional, Danner, Nils, additional, Posti, Jussi P, additional, Laukka, Dan, additional, Luoto, Teemu, additional, Rauhala, Minna, additional, Tetri, Sami, additional, Korhonen, Tommi K, additional, Satopää, Jarno, additional, Kivisaari, Riku, additional, Luostarinen, Teemu, additional, Schwartz, Christoph, additional, Czuba, Tomasz, additional, Taimela, Simo, additional, Lönnrot, Kimmo, additional, Järvinen, Teppo L N, additional, Ahmed, Abdirisak, additional, Areda, Tarmo, additional, Bartek, Jiri Jr, additional, Elomaa, Antti-Pekka, additional, Frantzén, Janek, additional, Haapala, Ilkka, additional, Haapasalo, Joonas, additional, Heikkilä, Juuso, additional, Hellman, Minttu, additional, Henttonen, Henna, additional, Huuska, Nora, additional, Järvinen, Teppo LN, additional, Jyrkkänen, Henna-Kaisa, additional, Kaipainen, Aku, additional, Kämäräinen, Olli-Pekka, additional, Kämppi, Hanna, additional, Kelahaara, Milla, additional, Klimko, Nikolai, additional, Knuutinen, Oula A, additional, Korhonen, Tommi, additional, Koskimäki, Janne, additional, Kovalainen, Anselmi, additional, Kuparinen, Xenia, additional, Lehecka, Martin, additional, Lehtimäki, Kai, additional, Luikku, Antti, additional, Luotonen, Janne, additional, Lustig-Tammi, Lauriina, additional, Maanpää, Henna-Riikka, additional, Määttä, Jenni, additional, Möttönen, Timo, additional, Netti, Eliisa, additional, Nevaharju-Sarantis, Laura, additional, Niemelä, Mika, additional, Niskakangas, Tero, additional, Nissinen, Mette, additional, Nurminen, Ville, additional, Oinas, Minna, additional, Ollonen, Teemu, additional, Östberg, Anna, additional, Oulasvirta, Elias, additional, Pantzar, Krista, additional, Piilonen, Katri, additional, Pohjola, Anni, additional, Polvivaara, Markus, additional, Raj, Rahul, additional, Rajala, Linnea, additional, Ranstam, Jonas, additional, Rezai Jahromi, Behnam, additional, Roiha, Miika, additional, Saarenpää, Ilkka, additional, Sajanti, Antti, additional, Salmi, Henrikki, additional, Shemeikka, Niina, additional, Sorto, Pia, additional, Thesleff, Tuomo, additional, Tuomisto, Maarit, additional, Vartiainen, Nuutti, additional, Vasankari, Ville, additional, Virta, Jyri, additional, Visuri, Mikko, additional, Walle, Paula, additional, and Zeiler, Frederick A, additional

Published
2024
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16. Correction to: Night‑time versus daytime surgical outcomes in chronic subdural hematomas: a post hoc analysis of the FINISH randomized trial.

Author

Oulasvirta, Elias, Knuutinen, Oula, Tommiska, Pihla, Kivisaari, Riku, Raj, Rahul, Ahmed, Abdirisak, Areda, Tarmo, Bartek, Jiri Jr, Czuba, Tomasz, Danner, Nils, Elomaa, Antti-Pekka, Frantzén, Janek, Haapala, Ilkka, Haapasalo, Joonas, Heikkilä, Juuso, Hellman, Minttu, Henttonen, Henna, Huuska, Nora, Järvinen, Teppo L. N., and Jyrkkänen, Henna-Kaisa

Subjects
HEMATOMA, MANUSCRIPTS
Abstract

The Correction Notice from Acta Neurochirurgica addresses the missing names of the FINISH study group in the original manuscript. The document provides a complete list of FINISH investigators involved in the study. The original article has been corrected, and Springer Nature remains neutral regarding jurisdictional claims and institutional affiliations. [Extracted from the article]

Published
2024
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21. Additional file 1 of In vivo assessment of Lewy body and beta-amyloid copathologies in idiopathic normal pressure hydrocephalus: prevalence and associations with clinical features and surgery outcome

Author

Giannini, Giulia, Baiardi, Simone, Dellavalle, Sofia, Zenesini, Corrado, Cevoli, Sabina, Danner, Nils, Jyrkkänen, Henna-Kaisa, Rossi, Marcello, Polischi, Barbara, Quadalti, Corinne, Stefanini, Camilla, Cortelli, Pietro, Milletti, David, Herukka, Sanna-Kaisa, Palandri, Giorgio, Leinonen, Ville, and Parchi, Piero

Abstract

Additional file 1: Table S1. Summary of evaluations in the included cohorts. Table S2. Demographic data and summary of α-syn RT-QuIC results in the CJD cohort. Table S3. Summary of demographic and clinical features and results of indicative biomarkers of DLB individuals. Table S4. Baseline clinical features of the Bologna PRO-HYDRO cohort and comparisons between α-synLB + and α-syn-LB -. Table S5. Comparisons between Aß + vs. Aß– subgroups of patients from the Bologna PRO-HYDRO cohort. Table S6. Comparisons between responders and non-responders 6 months after surgery.

Published
2022
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22. Cerebrospinal fluid dynamics in idiopathic intracranial hypertension : a literature review and validation of contemporary findings

Author

Kaipainen, Aku L., Martoma, Erik, Puustinen, Tero, Tervonen, Joona, Jyrkkänen, Henna Kaisa, Paterno, Jussi J., Kotkansalo, Anna, Rantala, Susanna, Vanhanen, Ulla, Leinonen, Ville, Lehto, Soili M., Iso-Mustajärvi, Matti, Elomaa, Antti Pekka, Qvarlander, Sara, Huuskonen, Terhi J., HUS Neurocenter, Clinicum, Department of Psychiatry, and University of Helsinki

Subjects
MECHANISM, PULSE PRESSURE, SAGITTAL SINUS, 3112 Neurosciences, Cerebrospinal fluid dynamics, 3126 Surgery, anesthesiology, intensive care, radiology, 3124 Neurology and psychiatry, Idiopathic intracranial hypertension, PSEUDOTUMOR CEREBRI, ACETAZOLAMIDE, ELASTANCE, CEREBRAL-BLOOD-FLOW, Cerebrospinal fluid pressure measurement, OUTFLOW, RESISTANCE, BARIATRIC SURGERY
Abstract

Publisher Copyright: © 2021, The Author(s). Background: Idiopathic intracranial hypertension (IIH) is a rare disease of unknown aetiology related possibly to disturbed cerebrospinal fluid (CSF) dynamics and characterised by elevated intracranial pressure (ICP) causing optic nerve atrophy if not timely treated. We studied CSF dynamics of the IIH patients based on the available literature and our well-defined cohort. Method: A literature review was performed from PubMed between 1980 and 2020 in compliance with the PRISMA guideline. Our study includes 59 patients with clinical, demographical, neuro-ophthalmological, radiological, outcome data, and lumbar CSF pressure measurements for suspicion of IIH; 39 patients had verified IIH while 20 patients did not according to Friedman’s criteria, hence referred to as symptomatic controls. Results: The literature review yielded 19 suitable studies; 452 IIH patients and 264 controls had undergone intraventricular or lumbar CSF pressure measurements. In our study, the mean CSF pressure, pulse amplitudes, power of respiratory waves (RESP), and the pressure constant (P0) were higher in IIH than symptomatic controls (p < 0.01). The mean CSF pressure was higher in IIH patients with psychiatric comorbidity than without (p < 0.05). In IIH patients without acetazolamide treatment, the RAP index and power of slow waves were also higher (p < 0.05). IIH patients with excess CSF around the optic nerves had lower relative pulse pressure coefficient (RPPC) and RESP than those without (p < 0.05). Conclusions: Our literature review revealed increased CSF pressure, resistance to CSF outflow and sagittal sinus pressure (SSP) as key findings in IIH. Our study confirmed significantly higher lumbar CSF pressure and increased CSF pressure waves and RAP index in IIH when excluding patients with acetazolamide treatment. In overall, the findings reflect decreased craniospinal compliance and potentially depleted cerebral autoregulation resulting from the increased CSF pressure in IIH. The increased slow waves in patients without acetazolamide may indicate issues in autoregulation, while increased P0 could reflect the increased SSP.

Published
2021

35. NRF2 regulates endothelial glycolysis and proliferation with miR-93 and mediates the effects of oxidized phospholipids on endothelial activation

Author

Kuosmanen, Suvi M, primary, Kansanen, Emilia, additional, Kaikkonen, Minna U, additional, Sihvola, Virve, additional, Pulkkinen, Kati, additional, Jyrkkänen, Henna-Kaisa, additional, Tuoresmäki, Pauli, additional, Hartikainen, Juha, additional, Hippeläinen, Mikko, additional, Kokki, Hannu, additional, Tavi, Pasi, additional, Heikkinen, Sami, additional, and Levonen, Anna-Liisa, additional

Published
2017
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36. Hapettuneiden ja nitrattujen rasvahappojen aktivoimat signaalitiet

Author

Jyrkkänen, Henna-Kaisa, Lääketieteen laitos, School of Medicine, Terveystieteiden tiedekunta, Lääketieteen laitos, Kliininen lääketiede, Faculty of Health Sciences, School of Medicine, Clinical Medicine, Terveystieteiden tiedekunta, and Faculty of Health Sciences

Subjects
medicine, lääketiede
Published
2013

39. Transcription factor Nrf2 mediated gene regulation and signaling in the endothelium

Author

Jyrkkänen, Henna-Kaisa, A.I. Virtanen -instituutti, A.I. Virtanen Institute for Molecular Sciences, Terveystieteiden tiedekunta, A.I. Virtanen -instituutti, Bioteknologia ja molekulaarinen lääketiede, Faculty of Health Sciences, A.I. Virtanen Institute for Molecular Sciences, Biotechnology and Molecular Medicine, Terveystieteiden tiedekunta, and Faculty of Health Sciences

Published
2011

40. Novel insights into the regulation of antioxidant-response-elementmediated gene expression by electrophiles: induction of the transcriptional repressor BACH1 by Nrf2

Author

Jyrkkänen, Henna-Kaisa, primary, Kuosmanen, Suvi, additional, Heinäniemi, Merja, additional, Laitinen, Heidi, additional, Kansanen, Emilia, additional, Mella-Aho, Eero, additional, Leinonen, Hanna, additional, Ylä-Herttuala, Seppo, additional, and Levonen, Anna-Liisa, additional

Published
2011
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42. Nrf2 Regulates Antioxidant Gene Expression Evoked by Oxidized Phospholipids in Endothelial Cells and Murine Arteries In Vivo

Author

Jyrkkänen, Henna-Kaisa, primary, Kansanen, Emilia, additional, Inkala, Matias, additional, Kivelä, Annukka M., additional, Hurttila, Hanna, additional, Heinonen, Suvi E., additional, Goldsteins, Gundars, additional, Jauhiainen, Suvi, additional, Tiainen, Satu, additional, Makkonen, Harri, additional, Oskolkova, Olga, additional, Afonyushkin, Taras, additional, Koistinaho, Jari, additional, Yamamoto, Masayuki, additional, Bochkov, Valery N., additional, Ylä-Herttuala, Seppo, additional, and Levonen, Anna-Liisa, additional

Published
2008
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43. Nrf2 Gene Transfer Induces Antioxidant Enzymes and Suppresses Smooth Muscle Cell Growth In Vitro and Reduces Oxidative Stress in Rabbit Aorta In Vivo

Author

Levonen, Anna-Liisa, primary, Inkala, Matias, additional, Heikura, Tommi, additional, Jauhiainen, Suvi, additional, Jyrkkänen, Henna-Kaisa, additional, Kansanen, Emilia, additional, Määttä, Kirsi, additional, Romppanen, Elina, additional, Turunen, Päivi, additional, Rutanen, Juha, additional, and Ylä-Herttuala, Seppo, additional

Published
2007
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44. In vivo assessment of Lewy body and beta-amyloid copathologies in idiopathic normal pressure hydrocephalus: prevalence and associations with clinical features and surgery outcome

Author

Giulia Giannini, Simone Baiardi, Sofia Dellavalle, Corrado Zenesini, Sabina Cevoli, Nils Danner, Henna-Kaisa Jyrkkänen, Marcello Rossi, Barbara Polischi, Corinne Quadalti, Camilla Stefanini, Pietro Cortelli, David Milletti, Sanna-Kaisa Herukka, Giorgio Palandri, Ville Leinonen, Piero Parchi, Giannini, Giulia, Baiardi, Simone, Dellavalle, Sofia, Zenesini, Corrado, Cevoli, Sabina, Danner, Nil, Jyrkkänen, Henna-Kaisa, Rossi, Marcello, Polischi, Barbara, Quadalti, Corinne, Stefanini, Camilla, Cortelli, Pietro, Milletti, David, Herukka, Sanna-Kaisa, Palandri, Giorgio, Leinonen, Ville, and Parchi, Piero

Subjects
Amyloid beta-Peptide, Idiopathic normal pressure hydrocephalu, tau Proteins, Cellular and Molecular Neuroscience, α-synuclein, Developmental Neuroscience, Peptide Fragment, Prevalence, Humans, Movement disorder, Aged, Lewy Bodie, Surgery outcome, Amyloid beta-Peptides, tau Protein, RT-QuIC, General Medicine, Biomarker, Hydrocephalus, Normal Pressure, Peptide Fragments, Real-time quaking-induced conversion assay, Cerebrospinal fluid, Lewy body, Neurology, alpha-Synuclein, Lewy Bodies, Biomarkers, Human
Abstract

Background Idiopathic normal pressure hydrocephalus (iNPH) is a clinico-radiological syndrome of elderly individuals likely sustained by different neurodegenerative changes as copathologies. Since iNPH is a potentially reversible condition, assessing neurodegenerative pathologies in vitam through CSF biomarkers and their influence on clinical features and surgical outcome represents crucial steps. Methods We measured α-synuclein seeding activity related to Lewy body (LB) pathology by the real-time quaking-induced conversion assay (RT-QuIC) and Alzheimer disease core biomarkers (proteins total-tau, phospho-tau, and amyloid-beta) by immunoassays in the cerebrospinal fluid (CSF) of 293 iNPH patients from two independent cohorts. To compare the prevalence of LB copathology between iNPH participants and a control group representative of the general population, we searched for α-synuclein seeding activity in 89 age-matched individuals who died of Creutzfeldt-Jakob disease (CJD). Finally, in one of the iNPH cohorts, we also measured the CSF levels of neurofilament light chain protein (NfL) and evaluated the association between all CSF biomarkers, baseline clinical features, and surgery outcome at 6 months. Results Sixty (20.5%) iNPH patients showed α-synuclein seeding activity with no significant difference between cohorts. In contrast, the prevalence observed in CJD was only 6.7% (p = 0.002). Overall, 24.0% of iNPH participants showed an amyloid-positive (A+) status, indicating a brain co-pathology related to Aβ deposition. At baseline, in the Italian cohort, α-synuclein RT-QuIC positivity was associated with higher scores on axial and upper limb rigidity (p = 0.003 and p = 0.011, respectively) and lower MMSEc scores (p = 0.003). A+ patients showed lower scores on the MMSEc (p = 0.037) than A- patients. Higher NfL levels were also associated with lower scores on the MMSEc (rho = -0.213; p = 0.021). There were no significant associations between CSF biomarkers and surgical outcome at 6 months (i.e. responders defined by decrease of 1 point on the mRankin scale). Conclusions Prevalent LB- and AD-related neurodegenerative pathologies affect a significant proportion of iNPH patients and contribute to cognitive decline (both) and motor impairment (only LB pathology) but do not significantly influence the surgical outcome at 6 months. Their effect on the clinical benefit after surgery over a more extended period remains to be determined.

Published
2022

45. Novel insights into the regulation of antioxidant-response-element-mediated gene expression by electrophiles: induction of the transcriptional repressor BACH1 by Nrf2.

Author

Jyrkkänen HK, Kuosmanen S, Heinäniemi M, Laitinen H, Kansanen E, Mella-Aho E, Leinonen H, Ylä-Herttuala S, and Levonen AL

Subjects
HEK293 Cells, Human Umbilical Vein Endothelial Cells, Humans, Isothiocyanates, Nitro Compounds pharmacology, Oleic Acids pharmacology, Sulfoxides, Thiocyanates pharmacology, Basic-Leucine Zipper Transcription Factors biosynthesis, Fanconi Anemia Complementation Group Proteins biosynthesis, NF-E2-Related Factor 2 physiology, Response Elements physiology
Abstract

A central mechanism in cellular defence against oxidative or electrophilic stress is mediated by transcriptional induction of genes via the ARE (antioxidant-response element), a cis-acting sequence present in the regulatory regions of genes involved in the detoxification and elimination of reactive oxidants and electrophiles. The ARE binds different bZIP (basic-region leucine zipper) transcription factors, most notably Nrf2 (nuclear factor-erythroid 2-related factor 2) that functions as a transcriptional activator via heterodimerization with small Maf proteins. Although ARE activation by Nrf2 is relatively well understood, the mechanisms by which ARE-mediated signalling is down-regulated are poorly known. Transcription factor BACH1 [BTB (broad-complex, tramtrack and bric-a-brac) and CNC (cap'n'collar protein) homology 1] binds to ARE-like sequences, functioning as a transcriptional repressor in a subset of ARE-regulated genes, thus antagonizing the activator function of Nrf2. In the present study, we have demonstrated that BACH1 itself is regulated by Nrf2 as it is induced by Nrf2 overexpression and by Nrf2-activating agents in an Nrf2-dependent manner. Furthermore, a functional ARE site was identified at +1411 from the transcription start site of transcript variant 2 of BACH1. We conclude that BACH1 is a bona fide Nrf2 target gene and that induction of BACH1 by Nrf2 may serve as a feedback-inhibitory mechanism for ARE-mediated gene regulation.

Published
2011
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