| Activation of a caspase-dependent oxidative damage response mediates TGFbeta1 apoptosis in rat hepatocytes. | |
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MedLine Citation:
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PMID: 12782012 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Activation of transforming growth factor-beta type 1- (TGFbeta1) mediated signaling occurs in response to cell injury affecting stem-type cells and hepatocytes in liver. In this work we used WB stemlike liver epithelial cells and p53-defective CWSV-1 nontumorigenic rat hepatocytes to investigate the possible roles of caspases and oxidative stress in TGFbeta1 signaling. TGFbeta1 significantly increased the level of 4-hydroxy-2-nonenal (4-HNE), a stable product of lipid peroxidation. In addition, TGFbeta1-treated cells exhibited activation of caspases that accompanied by enhanced cleavage of the caspase substrate poly(ADP)-ribose polymerase (PARP) and induction of apoptosis. WB cells were twice as sensitive as sensitive as CWSV-1 cells to induction of TGFbeta1 apoptosis. TGFbeta1-apoptosis was significantly reduced when cells were treated with TGFbeta1 in the presence of inhibitors of caspase-1, -3, -8, and -9. Importantly, in addition to suppression of apoptosis, treatment of cells with the caspase-3 inhibitor Z-DEVD-FMK in the presence of TGFbeta1 suppressed the formation 4-HNE and restored mitotic activity. Together, these data suggest TGFbeta1 induces activation of a caspase signaling cascade that includes an oxidative damage response, PARP cleavage, and apoptosis that do not require intact p53 in rat hepatocytes. |
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Authors:
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Craig D Albright; Crystal Borgman; Corneliu N Craciunescu |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Experimental and molecular pathology Volume: 74 ISSN: 0014-4800 ISO Abbreviation: Exp. Mol. Pathol. Publication Date: 2003 Jun |
Date Detail:
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Created Date: 2003-06-03 Completed Date: 2003-07-01 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0370711 Medline TA: Exp Mol Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 256-61 Citation Subset: IM |
Affiliation:
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Department of Nutrition, School of Public Health and School of Medicine, University of North Carolina, Chapel Hill 27599-7461, USA. cdalbrig@email.unc.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aldehydes
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metabolism Animals Apoptosis / drug effects, physiology* Caspase 3 Caspases / antagonists & inhibitors, metabolism* Cell Count Cell Division Cell Line Cell Transformation, Viral Enzyme Inhibitors / pharmacology Hepatocytes / drug effects, enzymology*, pathology In Situ Nick-End Labeling Oligopeptides / pharmacology Oxidative Stress Poly(ADP-ribose) Polymerases / metabolism Rats Signal Transduction Transforming Growth Factor beta / metabolism*, pharmacology Transforming Growth Factor beta1 Tumor Suppressor Protein p53 / deficiency |
| Chemical | |
Reg. No./Substance:
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0/Aldehydes; 0/Enzyme Inhibitors; 0/Oligopeptides; 0/Tgfb1 protein, rat; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1; 0/Tumor Suppressor Protein p53; 0/benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; 29343-52-0/4-hydroxy-2-nonenal; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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