| Bax cleavage implicates caspase-dependent H2O2-induced apoptosis of hepatocytes. | |
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MedLine Citation:
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PMID: 12579342 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Oxidative stress plays an important role in the development of ischemia/reperfusion (I/R)-induced apoptosis of hepatocytes. We aimed to examine the involvement of caspases and calpains in H2O2-induced hepatic cell apoptosis. TUNEL-positive apoptotic cells appeared in parallel with poly(ADP-ribose) polymerase (PARP) cleavage and procaspase-3 proteolysis by H2O2 treatment in a dose-dependent manner (250-1,000 micro M). Bcl-xL and intact Bax expression levels decreased when H2O2 was >250 micro M. The cleaved form of Bax appeared prior to caspase-3 activation, increasing in a dose-dependent manner. A pan-caspase inhibitor, Z-VAD-fmk, completely blocked H2O2-induced procaspase-3 proteolysis and PARP cleavage without changing Bax cleavage, but partially attenuated H2O2-induced apoptosis. Calpeptin, a calpain inhibitor, did not inhibit caspase-3 activation, Bax cleavage or apoptosis. Our results indicate that Bax cleavage is upstream signal of caspase-dependent apoptosis in hepatocytes exposed to H2O2, but not independent upon calpain. Molecular targeting of Bax cleavage may allow the development of strategies to prevent hepatic I/R injury. |
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Authors:
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Hiroaki Tamura; Akira Ohtsuru; Yukio Kamohara; Hikaru Fujioka; Katsuhiko Yanaga; Takashi Kanematsu; Shunichi Yamashita |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: International journal of molecular medicine Volume: 11 ISSN: 1107-3756 ISO Abbreviation: Int. J. Mol. Med. Publication Date: 2003 Mar |
Date Detail:
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Created Date: 2003-02-11 Completed Date: 2004-01-13 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9810955 Medline TA: Int J Mol Med Country: Greece |
Other Details:
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Languages: eng Pagination: 369-74 Citation Subset: IM |
Affiliation:
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Department of Surgery II, Graduate School of Biochemical Sciences, Nagasaki University, Nagasaki 852-8501, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Chloromethyl Ketones
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pharmacology Apoptosis / drug effects* Calpain / antagonists & inhibitors, drug effects, metabolism Caspase 3 Caspases / antagonists & inhibitors, drug effects, metabolism* Cell Line Cysteine Proteinase Inhibitors / pharmacology DNA Fragmentation / drug effects Dipeptides / pharmacology Dose-Response Relationship, Drug Enzyme Activation Enzyme Precursors / antagonists & inhibitors, drug effects, metabolism Hepatocytes / drug effects, physiology* Humans Hydrogen Peroxide / pharmacology* Oxidants / pharmacology* Poly(ADP-ribose) Polymerases / metabolism Proto-Oncogene Proteins / drug effects, metabolism* Proto-Oncogene Proteins c-bcl-2 / drug effects, metabolism bcl-2-Associated X Protein bcl-X Protein |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Chloromethyl Ketones; 0/BAX protein, human; 0/BCL2L1 protein, human; 0/Cysteine Proteinase Inhibitors; 0/Dipeptides; 0/Enzyme Precursors; 0/Oxidants; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2-Associated X Protein; 0/bcl-X Protein; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 117591-20-5/calpeptin; 7722-84-1/Hydrogen Peroxide; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Calpain; 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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