| Bcl-2 overexpression in hepatic stellate cell line CFSC-2G, induces a pro-fibrotic state. | |
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MedLine Citation:
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PMID: 20594261 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND AIM: Development of hepatic fibrosis is a complex process that involves oxidative stress (OS) and an altered balance between pro- and anti-apoptotic molecules. Since Bcl-2 overexpression preserves viability against OS, our objective was to address the effect of Bcl-2 overexpression in the hepatic stellate cells (HSC) cell-line CFSC-2G under acetaldehyde and H(2)O(2) challenge, and explore if it protects these cells against OS, induces replicative senescence and/or modify extracellular matrix (ECM) remodeling potential. METHODS: To induce Bcl-2 overexpression, HSC cell line CFSC-2G was transfected by lipofection technique. Green fluorescent protein-only CFSC-2G cells were used as a control. Cell survival after H(2)O(2) treatment and total protein oxidation were assessed. To determine cell cycle arrest, proliferation-rate, DNA synthesis and senescence were assessed. Matrix metalloproteinases (MMP), tissue-inhibitor of MMP (TIMP), transglutaminases (TG) and smooth muscle a-actin (alpha-SMA) were evaluated by western blot in response to acetaldehyde treatment as markers of ECM remodeling capacity in addition to transforming growth factor-beta (TGF-beta) mRNA. RESULTS: Cells overexpressing Bcl-2 survived approximately 20% more than control cells when exposed to H(2)O(2) and approximately 35% proteins were protected from oxidation, but Bcl-2 did not slow proliferation or induced senescence. Bcl-2 overexpression did not change alpha-SMA levels, but it increased TIMP-1 (55%), tissue transglutaminases (tTG) (25%) and TGF-beta mRNA (49%), when exposed to acetaldehyde, while MMP-13 content decreased (47%). CONCLUSIONS: Bcl-2 overexpression protected HSC against oxidative stress but it did not induce replicative senescence. It increased TIMP-1, tTG and TGF-beta mRNA levels and decreased MMP-13 content, suggesting that Bcl-2 overexpression may play a key role in the progression of fibrosis in chronic liver diseases. |
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Authors:
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Viridiana Y González-Puertos; Elizabeth Hernández-Pérez; Natalia Nuño-Lámbarri; José L Ventura-Gallegos; Norma E López-Diázguerrero; Guillermo Robles-Díaz; María C Gutiérrez-Ruiz; Mina Konigsberg |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of gastroenterology and hepatology Volume: 25 ISSN: 1440-1746 ISO Abbreviation: J. Gastroenterol. Hepatol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-02 Completed Date: 2010-10-18 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8607909 Medline TA: J Gastroenterol Hepatol Country: Australia |
Other Details:
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Languages: eng Pagination: 1306-14 Citation Subset: IM |
Affiliation:
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Health and Sciences Department, Biological and Health Sciences Division, Metropolitan Independent University, México, DF, México. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetaldehyde
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pharmacology Actins / metabolism Animals Cell Aging Cell Line Cell Proliferation DNA Replication Dose-Response Relationship, Drug Extracellular Matrix / metabolism GTP-Binding Proteins / metabolism Hepatic Stellate Cells / drug effects, metabolism*, pathology Humans Hydrogen Peroxide / pharmacology Liver Cirrhosis / genetics, metabolism*, pathology Matrix Metalloproteinase 13 / metabolism Oxidants / pharmacology Oxidative Stress Proto-Oncogene Proteins c-bcl-2 / genetics, metabolism* RNA, Messenger / metabolism Rats Recombinant Fusion Proteins / metabolism Time Factors Tissue Inhibitor of Metalloproteinase-1 / metabolism Transfection Transforming Growth Factor beta / genetics Transglutaminases / metabolism Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/Oxidants; 0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Messenger; 0/Recombinant Fusion Proteins; 0/Tissue Inhibitor of Metalloproteinase-1; 0/Transforming Growth Factor beta; 0/smooth muscle actin, rat; 75-07-0/Acetaldehyde; 7722-84-1/Hydrogen Peroxide; EC 2.3.2.-/transglutaminase 2; EC 2.3.2.13/Transglutaminases; EC 3.4.24.-/Matrix Metalloproteinase 13; EC 3.4.24.-/Mmp13 protein, rat; EC 3.6.1.-/GTP-Binding Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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