11 results on '"Golenkina, S."'
Search Results
2. Analysis of clusterin gene (CLU/APOJ) polymorphism in Alzheimer’s disease patients and in normal cohorts from Russian populations
- Author
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Golenkina, S. A., Goltsov, A. Yu., Kuznetsova, I. L., Grigorenko, A. P., Andreeva, T. V., Reshetov, D. A., Kunizheva, S. S., Shagam, L. I., Morozova, I. Yu., Goldenkova-Pavlova, I. V., Shimshilashvili, H., Vyacheslavova, A. O., Faskhutdinova, G., Gareeva, A. E., Zainullina, A. G., Kazantseva, A.V., Khusnutdinova, E. K., Puzyrev, V. P., Stepanov, V. A., Kolotvin, A. V., Samokhodskaya, L. M., Selezneva, N. D., Gavrilova, S. I., and Rogaev, E. I.
- Published
- 2010
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3. [Analysis of clusterin gene (CLU/APOJ) polymorphism in Alzheimer's disease patients and in normal cohorts from Russian populations]
- Author
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Golenkina, S. A., Gol Tsov, A. I., Kuznetsova, I. L., Grigorenko, A. P., Andreeva, T. V., Reshetov, D. A., Kunizheva, S. S., Shagam, L. I., Morozova, I. I., Goldenkova-Pavlova, I. V., Shimshilashvili, K., Viacheslavova, A. O., Faskhutdinova, G., Gareeva, A. E., Zaǐnullina, A. G., Khusnutdinova, E. K., Puzyrev, V. P., Stepanov, V. A., Kolotvin, A. V., Samokhodskaia, L. M., Selezneva, N. D., Svetlana Gavrilova, and Rogaev, E. I.
- Subjects
Adult ,Aged, 80 and over ,Male ,Polymorphism, Genetic ,Middle Aged ,Russia ,Cohort Studies ,Clusterin ,Gene Frequency ,Alzheimer Disease ,Humans ,Female ,Alleles ,Aged ,Genome-Wide Association Study - Abstract
Three genes mutations in which cause familial forms of Alzheimer's disease are known to date:PSEN1, PSEN2 and APP; and APOE gene polymorphism is a strong risk factor for Alzheimer's disease. We have evaluated allele and genotype frequency distribution of rs11136000 polymorphism in clusterin (CLU) gene (or apolipoprotein J, APOJ) in populations of three Russian regions and i nAlzheimhner's diseasepatients. Genome-wideassociation studies in samples from several European populations have recently revealed highly significant association o fCLU gene with AD (p = 8.5 x 10(-10)). We found no differences in allele and genotype frequencies of rs11136000 between populations from Moscow, Ural and Siberia regions. The allele frequencies are close to those in European populations. The genetic association analysis in cohort of Alzheimer's disease patients and normal individuals (500 individuals ineach group) revealed no significant association of the rs11136000 polymorphism in CLU with Alzheimer's disease in Russian populations. Although our resultsdo not confirm the role of CLU gene as a majorgenetic factor forcommon form of Alzheimer's disease, the data do not rule out the possibility of modest effect of CLU and interaction between CLU and APOE genotypes in etiology of Alzheimer's disease.
4. Mitochondrial fusion and altered beta-oxidation drive muscle wasting in a Drosophila cachexia model.
- Author
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Dark C, Ali N, Golenkina S, Dhyani V, Blazev R, Parker BL, Murphy KT, Lynch GS, Senapati T, Millard SS, Judge SM, Judge AR, Giri L, Russell SM, and Cheng LY
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- Mice, Animals, Humans, Cachexia etiology, Cachexia metabolism, Drosophila metabolism, Mitochondrial Dynamics, Muscular Atrophy pathology, Muscle, Skeletal metabolism, Lipids, Insulin-Like Growth Factor Binding Proteins metabolism, Colonic Neoplasms metabolism, Insulins metabolism, Drosophila Proteins genetics, Drosophila Proteins metabolism
- Abstract
Cancer cachexia is a tumour-induced wasting syndrome, characterised by extreme loss of skeletal muscle. Defective mitochondria can contribute to muscle wasting; however, the underlying mechanisms remain unclear. Using a Drosophila larval model of cancer cachexia, we observed enlarged and dysfunctional muscle mitochondria. Morphological changes were accompanied by upregulation of beta-oxidation proteins and depletion of muscle glycogen and lipid stores. Muscle lipid stores were also decreased in Colon-26 adenocarcinoma mouse muscle samples, and expression of the beta-oxidation gene CPT1A was negatively associated with muscle quality in cachectic patients. Mechanistically, mitochondrial defects result from reduced muscle insulin signalling, downstream of tumour-secreted insulin growth factor binding protein (IGFBP) homologue ImpL2. Strikingly, muscle-specific inhibition of Forkhead box O (FOXO), mitochondrial fusion, or beta-oxidation in tumour-bearing animals preserved muscle integrity. Finally, dietary supplementation with nicotinamide or lipids, improved muscle health in tumour-bearing animals. Overall, our work demonstrates that muscle FOXO, mitochondria dynamics/beta-oxidation and lipid utilisation are key regulators of muscle wasting in cancer cachexia., (© 2024. The Author(s).)
- Published
- 2024
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5. Convergent insulin and TGF-β signalling drives cancer cachexia by promoting aberrant fat body ECM accumulation in a Drosophila tumour model.
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Bakopoulos D, Golenkina S, Dark C, Christie EL, Sánchez-Sánchez BJ, Stramer BM, and Cheng LY
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- Animals, Drosophila, Insulin, Fat Body metabolism, Adipose Tissue metabolism, Transforming Growth Factor beta, Cachexia etiology, Cachexia metabolism, Neoplasms complications
- Abstract
In this study, we found that in the adipose tissue of wildtype animals, insulin and TGF-β signalling converge via a BMP antagonist short gastrulation (sog) to regulate ECM remodelling. In tumour bearing animals, Sog also modulates TGF-β signalling to regulate ECM accumulation in the fat body. TGF-β signalling causes ECM retention in the fat body and subsequently depletes muscles of fat body-derived ECM proteins. Activation of insulin signalling, inhibition of TGF-β signalling, or modulation of ECM levels via SPARC, Rab10 or Collagen IV in the fat body, is able to rescue tissue wasting in the presence of tumour. Together, our study highlights the importance of adipose ECM remodelling in the context of cancer cachexia., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)
- Published
- 2023
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6. Tumor-derived MMPs regulate cachexia in a Drosophila cancer model.
- Author
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Lodge W, Zavortink M, Golenkina S, Froldi F, Dark C, Cheung S, Parker BL, Blazev R, Bakopoulos D, Christie EL, Wimmer VC, Duckworth BC, Richardson HE, and Cheng LY
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- Animals, Basement Membrane metabolism, Drosophila metabolism, Extracellular Matrix metabolism, Muscular Atrophy metabolism, Adipose Tissue metabolism, Matrix Metalloproteinases metabolism, Muscle, Skeletal metabolism, Neoplasms metabolism
- Abstract
Cachexia, the wasting syndrome commonly observed in advanced cancer patients, accounts for up to one-third of cancer-related mortalities. We have established a Drosophila larval model of organ wasting whereby epithelial overgrowth in eye-antennal discs leads to wasting of the adipose tissue and muscles. The wasting is associated with fat-body remodeling and muscle detachment and is dependent on tumor-secreted matrix metalloproteinase 1 (Mmp1). Mmp1 can both modulate TGFβ signaling in the fat body and disrupt basement membrane (BM)/extracellular matrix (ECM) protein localization in both the fat body and the muscle. Inhibition of TGFβ signaling or Mmps in the fat body/muscle using a QF2-QUAS binary expression system rescues muscle wasting in the presence of tumor. Altogether, our study proposes that tumor-derived Mmps are central mediators of organ wasting in cancer cachexia., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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7. Glial Hedgehog signalling and lipid metabolism regulate neural stem cell proliferation in Drosophila.
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Dong Q, Zavortink M, Froldi F, Golenkina S, Lam T, and Cheng LY
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- Animals, Cell Proliferation, Drosophila metabolism, Drosophila melanogaster genetics, Drosophila melanogaster metabolism, Hedgehog Proteins genetics, Lipid Metabolism, Drosophila Proteins genetics, Drosophila Proteins metabolism, Neural Stem Cells metabolism
- Abstract
The final size and function of the adult central nervous system (CNS) are determined by neuronal lineages generated by neural stem cells (NSCs) in the developing brain. In Drosophila, NSCs called neuroblasts (NBs) reside within a specialised microenvironment called the glial niche. Here, we explore non-autonomous glial regulation of NB proliferation. We show that lipid droplets (LDs) which reside within the glial niche are closely associated with the signalling molecule Hedgehog (Hh). Under physiological conditions, cortex glial Hh is autonomously required to sustain niche chamber formation. Upon FGF-mediated cortex glial overgrowth, glial Hh non-autonomously activates Hh signalling in the NBs, which in turn disrupts NB cell cycle progression and its ability to produce neurons. Glial Hh's ability to signal to NB is further modulated by lipid storage regulator lipid storage droplet-2 (Lsd-2) and de novo lipogenesis gene fatty acid synthase 1 (Fasn1). Together, our data suggest that glial-derived Hh modified by lipid metabolism mechanisms can affect the neighbouring NB's ability to proliferate and produce neurons., (© 2021 The Authors.)
- Published
- 2021
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8. Exploiting Drosophila melanogaster Wing Imaginal Disc Eversion to Screen for New EMT Effectors.
- Author
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Golenkina S, Manhire-Heath R, and Murray MJ
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- Animals, Drosophila Proteins metabolism, Drosophila melanogaster, Imaginal Discs metabolism, Phenotype, Wings, Animal cytology, Wings, Animal growth & development, Drosophila Proteins genetics, Epithelial-Mesenchymal Transition, Genetic Techniques, Imaginal Discs cytology, Tissue Culture Techniques methods
- Abstract
In the early stages of Drosophila melanogaster (Drosophila) metamorphosis, a partial epithelial-mesenchymal transition (pEMT) takes place in the peripodial epithelium of wing imaginal discs. Blocking this pEMT results in adults with internalized wings and missing thoracic tissue. Using peripodial GAL4 drivers, GAL80
ts temporal control, and UAS RNAi transgenes, one can use these phenotypes to screen for genes involved in the pEMT. Dominant modifier tests can then be employed to identify genetic enhancers and suppressors. To analyze a gene's role in the pEMT, one can then visualize peripodial cells in vivo at the time of eversion within the pupal case using live markers, and by dissecting, fixing, and immunostaining the prepupae. Alternatively, one can analyze the pEMT ex vivo by dissecting out wing discs and culturing them in the presence of ecdysone to induce eversion. This can provide a clearer view of the cellular processes involved and permit drug treatments to be easily applied.- Published
- 2021
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9. A genome-wide Drosophila epithelial tumorigenesis screen identifies Tetraspanin 29Fb as an evolutionarily conserved suppressor of Ras-driven cancer.
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Zoranovic T, Manent J, Willoughby L, Matos de Simoes R, La Marca JE, Golenkina S, Cuiping X, Gruber S, Angjeli B, Kanitz EE, Cronin SJF, Neely GG, Wernitznig A, Humbert PO, Simpson KJ, Mitsiades CS, Richardson HE, and Penninger JM
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- Animals, Animals, Genetically Modified, Carcinogenesis genetics, Drosophila Proteins metabolism, Drosophila melanogaster genetics, Epithelial Cells metabolism, Epithelial Cells pathology, Female, Genes, ras, Genetic Testing methods, Humans, IMP Dehydrogenase metabolism, Male, Mice, Neoplasms metabolism, Neoplasms pathology, Oncogenes, Signal Transduction, Tetraspanin 29 metabolism, Tumor Suppressor Proteins genetics, Drosophila Proteins genetics, IMP Dehydrogenase genetics, Neoplasms genetics, Tetraspanin 29 genetics
- Abstract
Oncogenic mutations in the small GTPase Ras contribute to ~30% of human cancers. However, Ras mutations alone are insufficient for tumorigenesis, therefore it is paramount to identify cooperating cancer-relevant signaling pathways. We devised an in vivo near genome-wide, functional screen in Drosophila and discovered multiple novel, evolutionarily-conserved pathways controlling Ras-driven epithelial tumorigenesis. Human gene orthologs of the fly hits were significantly downregulated in thousands of primary tumors, revealing novel prognostic markers for human epithelial tumors. Of the top 100 candidate tumor suppressor genes, 80 were validated in secondary Drosophila assays, identifying many known cancer genes and multiple novel candidate genes that cooperate with Ras-driven tumorigenesis. Low expression of the confirmed hits significantly correlated with the KRASG12 mutation status and poor prognosis in pancreatic cancer. Among the novel top 80 candidate cancer genes, we mechanistically characterized the function of the top hit, the Tetraspanin family member Tsp29Fb, revealing that Tsp29Fb regulates EGFR signaling, epithelial architecture and restrains tumor growth and invasion. Our functional Drosophila screen uncovers multiple novel and evolutionarily conserved epithelial cancer genes, and experimentally confirmed Tsp29Fb as a key regulator of EGFR/Ras induced epithelial tumor growth and invasion., Competing Interests: AW is affiliated with Boehringer Ingelheim RCV GmbH & Co KG. Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria has no competing interests with this study.
- Published
- 2018
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10. Frazzled can act through distinct molecular pathways in epithelial cells to regulate motility, apical constriction, and localisation of E-Cadherin.
- Author
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Golenkina S, Chaturvedi V, Saint R, and Murray MJ
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- Adherens Junctions metabolism, Amino Acid Motifs, Animals, Animals, Genetically Modified, Armadillo Domain Proteins metabolism, Cell Cycle Proteins, Cell Movement, Cell Polarity, Cell Shape, Cell Surface Extensions metabolism, Drosophila Proteins chemistry, Drosophila Proteins genetics, Drosophila Proteins metabolism, Drosophila melanogaster cytology, Drosophila melanogaster genetics, Drosophila melanogaster growth & development, Epithelial Cells metabolism, Gene Expression Regulation, Developmental, Imaginal Discs cytology, Integrins physiology, Larva, Myosins metabolism, Netrin Receptors chemistry, Netrin Receptors genetics, Phosphorylation, Protein Processing, Post-Translational, Recombinant Proteins metabolism, Signal Transduction, Transcription Factors metabolism, Transgenes, rac GTP-Binding Proteins physiology, rho GTP-Binding Proteins physiology, Cadherins metabolism, Drosophila Proteins physiology, Drosophila melanogaster metabolism, Epithelial Cells cytology, Netrin Receptors physiology
- Abstract
Netrin receptors of the DCC/NEO/UNC-40/Frazzled family have well established roles in cell migration and axon guidance but can also regulate epithelial features such as adhesion, polarity and adherens junction (AJ) stability. Previously, we have shown that overexpression of Drosophila Frazzled (Fra) in the peripodial epithelium (PE) inhibits wing disc eversion and also generates cellular protrusions typical of motile cells. Here, we tested whether the molecular pathways by which Fra inhibits eversion are distinct from those driving motility. We show that in disc proper (DP) epithelial cells Fra, in addition to inducing F-Actin rich protrusions, can affect localization of AJ components and columnar cell shape. We then show that these phenotypes have different requirements for the three conserved Fra cytoplasmic P-motifs and for downstream genes. The formation of protrusions required the P3 motif of Fra, as well as integrins (mys and mew), the Rac pathway (Rac1, wave and, arpc3) and myosin regulatory light chain (Sqh). In contrast, apico-basal cell shape change, which was accompanied by increased myosin phosphorylation, was critically dependent upon the P1 motif and was promoted by RhoGef2 but inhibited by Rac1. Fra also caused a loss of AJ proteins (DE-Cad and Arm) from basolateral regions of epithelial cells. This phenotype required all 3 P-motifs, and was dependent upon the polarity factor par6. par6 was not required for protrusions or cell shape change, but was required to block eversion suggesting that control of AJ components may underlie the ability of Fra to promote epithelial stability. The results imply that multiple molecular pathways act downstream of Fra in epithelial cells.
- Published
- 2018
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11. Netrin-dependent downregulation of Frazzled/DCC is required for the dissociation of the peripodial epithelium in Drosophila.
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Manhire-Heath R, Golenkina S, Saint R, and Murray MJ
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- Animals, Down-Regulation, Drosophila growth & development, Drosophila Proteins, Epithelium physiology, Female, Membrane Proteins metabolism, Metamorphosis, Biological, Netrin Receptors, Netrin-1, Netrins, Proteasome Endopeptidase Complex metabolism, Receptors, Cell Surface physiology, Adherens Junctions physiology, Drosophila metabolism, Nerve Growth Factors metabolism, Receptors, Cell Surface metabolism, Tumor Suppressor Proteins metabolism, Wings, Animal growth & development
- Abstract
Netrins are secreted chemoattractants with roles in axon guidance, cell migration and epithelial plasticity. Netrin-1 also promotes the survival of metastasized cells by inhibiting the pro-apoptotic effects of its receptor Deleted in Colorectal Carcinoma (DCC). Here we report that Netrins can also regulate epithelial dissociation during Drosophila wing eversion. During eversion, peripodial epithelial cells lose apico-basal polarity and adherens junctions, and become migratory and invasive--a process similar to an epithelial-mesenchymal transition. Loss of netrinA inhibits the breakdown of cell-cell junctions, leading to eversion failure. In contrast, the Netrin receptor Frazzled blocks eversion when overexpressed, whereas frazzled RNAi accelerates eversion in vitro. In peripodial cells Frazzled is endocytosed, and undergoes NetA-dependent degradation, which is required for eversion. Finally, we provide evidence that Frazzled acts through the ERM-family protein Moesin to inhibit eversion. This mechanism may also help explain the role of Netrin and DCC in cancer metastasis.
- Published
- 2013
- Full Text
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