| Inhibitors of cysteine cathepsin and calpain do not prevent ultraviolet-B-induced apoptosis in human keratinocytes and HeLa cells. | |
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MedLine Citation:
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PMID: 15148608 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Caspases, members of the cysteine protease family, execute UVB-induced apoptosis in several cell lines and keratinocytes. Several researchers investigating UVB-induced apoptosis have demonstrated a dose-dependent protective effect of the synthetic peptide caspase inhibitor zVAD-fmk. However, zVAD-fmk displays a dose-dependent protective effect against UVB-induced apoptosis, even at doses higher than those required to block all known proapoptotic caspases. In addition, it is known that zVAD-fmk also inhibits other cysteine proteases including cathepsins and calpains, and these proteases have recently been demonstrated to play a role in the execution of programmed cell death induced by other stimuli, e.g. TNF-alpha. The purpose of the present study was therefore to investigate whether inhibitors of cysteine cathepsins and calpains could prevent UVB-induced apoptosis in HeLa cells and keratinocytes. This was done by investigating the effect of the irreversible cysteine protease inhibitor zFA-fmk, the cathepsin B inhibitor CA-074-Me and the calpain inhibitor ALLN on the viability of UVB-irradiated human keratinocytes and HeLa cells. At concentrations of 10 microM and above zVAD-fmk conferred partial dose-dependent protection against UVB-induced apoptosis in HeLa cells and keratinocytes. Moreover, caspase-3 activity was completely blocked at zVAD-fmk concentrations of 1 microM in HeLa cells. This indicates that caspase-independent mechanisms could be involved in UVB-induced apoptosis. However, the protease inhibitors zFA-fmk, CA-074-Me and ALLN all failed to prevent UVB-induced apoptosis in HeLa cells and keratinocytes. In conclusion, the protective effect of zVAD-fmk at high concentrations indicates that other proteases than caspases are active in the execution of UVB-induced apoptosis but further studies are needed to identify these proteases. |
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Authors:
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Bo Bang; Ole Baadsgaard; Lone Skov; Marja Jäättelä |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2004-05-18 |
Journal Detail:
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Title: Archives of dermatological research Volume: 296 ISSN: 0340-3696 ISO Abbreviation: Arch. Dermatol. Res. Publication Date: 2004 Jul |
Date Detail:
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Created Date: 2004-07-27 Completed Date: 2005-01-31 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8000462 Medline TA: Arch Dermatol Res Country: Germany |
Other Details:
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Languages: eng Pagination: 67-73 Citation Subset: IM |
Copyright Information:
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Copyright 2004 Springer-Verlag |
Affiliation:
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Department of Dermatology, Gentofte Hospital, Copenhagen, Denmark. bb22@bbh.hosp.dk |
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*, physiology, radiation effects Calpain / antagonists & inhibitors Caspases / antagonists & inhibitors Cathepsins / antagonists & inhibitors Cells, Cultured Cysteine Proteinase Inhibitors / pharmacology* Dipeptides / pharmacology Hela Cells Humans Keratinocytes / cytology, drug effects, radiation effects Ketones / pharmacology Leupeptins / pharmacology Phospholipases A / metabolism Ultraviolet Rays |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Chloromethyl Ketones; 0/CA 074 methyl ester; 0/Cysteine Proteinase Inhibitors; 0/Dipeptides; 0/Ketones; 0/Leupeptins; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 110044-82-1/acetylleucyl-leucyl-norleucinal; 96922-64-4/MDL 201053; EC 3.1.1.-/Phospholipases A; EC 3.4.-/Cathepsins; EC 3.4.22.-/Calpain; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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