| Roles of cathepsins in reperfusion-induced apoptosis in cultured astrocytes. | |
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MedLine Citation:
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PMID: 12421595 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Astrocytic apoptosis may play a role in the central nervous system injury. We previously showed that reperfusion of cultured astrocytes with normal medium after exposure to hydrogen peroxide (H(2)O(2))-containing medium causes apoptosis. This study examines the involvement of the lysosomal enzymes cathepsins B and D in the astrocytic apoptosis. Reperfusion after exposure to H(2)O(2) caused a marked increase in caspase-3 and cathepsin D activities and a marked decrease in cathepsin B activity. Pepstatin A, an inhibitor of cathepsin D, and acetyl-L-aspartyl-L-methionyl-L-glutaminyl-L-aspart-1-aldehyde (Ac-DMQD-CHO), a specific inhibitor of caspase-3, blocked the H(2)O(2)-induced decrease in cell viability and DNA ladder formation in cultured rat astrocytes. The (L-3-trans-(propylcarbamoyl)oxirane-2-carbonyl)-L-isoleucyl-L-proline methyl ester (CA074 Me), a specific inhibitor of cathepsin B, did not affect the H(2)O(2)-induced cell injury. On the other hand, CA074 Me decreased cell viability with DNA ladder formation when cultured in the presence of Ac-DMQD-CHO. This caspase-independent apoptosis was attenuated by the addition of the cathepsin D inhibitor pepstatin A. Caspase-3 like activity was markedly inhibited by Ac-DMQD-CHO and partially by pepstatin A. Pepstatin A and CA074 Me inhibited cathepsin B and cathepsin D activities, respectively, in the presence and absence of Ac-DMQD-CHO. These results suggest that cathepsins B and D are involved in astrocytic apoptosis: cathepsin D acts as a death-inducing factor upstream of caspase-3 and the caspase-independent apoptosis is regulated antagonistically by cathepsins B and D. |
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Authors:
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Kazuhiro Takuma; Makiko Kiriu; Koichi Mori; Eibai Lee; Riyo Enomoto; Akemichi Baba; Toshio Matsuda |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Neurochemistry international Volume: 42 ISSN: 0197-0186 ISO Abbreviation: Neurochem. Int. Publication Date: 2003 Jan |
Date Detail:
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Created Date: 2002-11-07 Completed Date: 2003-01-21 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8006959 Medline TA: Neurochem Int Country: England |
Other Details:
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Languages: eng Pagination: 153-9 Citation Subset: IM |
Affiliation:
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Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, High Technology Research Center, Kobe Gakuin University, Kobe 651-2180, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / physiology Astrocytes / pathology* Caspase 3 Caspases / antagonists & inhibitors, metabolism Cathepsin B / antagonists & inhibitors, physiology Cathepsin D / antagonists & inhibitors, physiology Cathepsins / antagonists & inhibitors, physiology* Cell Survival / drug effects Cells, Cultured DNA / biosynthesis, genetics Enzyme Inhibitors / pharmacology Hydrogen Peroxide / toxicity Peptide Hydrolases / metabolism Rats Rats, Wistar Reperfusion Injury / pathology* |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 7722-84-1/Hydrogen Peroxide; 9007-49-2/DNA; EC 3.4.-/Cathepsins; EC 3.4.-/Peptide Hydrolases; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases; EC 3.4.22.1/Cathepsin B; EC 3.4.23.5/Cathepsin D |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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