| Hydrogen peroxide-induced apoptosis in HL-60 cells requires caspase-3 activation. | |
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MedLine Citation:
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PMID: 10193575 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Apoptosis has been associated with oxidative stress in biological systems. Caspases have been considered to play a pivotal role in the execution phase of apoptosis. However, which caspases function as executioners in reactive oxygen species (ROS)-induced apoptosis is not known. The present study was performed to identify the major caspases acting in ROS-induced apoptosis. Treatment of HL-60 cells with 50 microM hydrogen peroxide (H2O2) for 4 h induced the morphological changes such as condensed and/or fragmented nuclei, increase in caspase-3 subfamily protease activities, reduction of the procaspase-3 and a DNA fragmentation. To determine the role of caspases in H2O2-induced apoptosis, caspase inhibitors, acetyl-Tyr-Val-Ala-Asp-chloromethyl ketone (Ac-YVAD-cmk), acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO) and acetyl-Val-Glu-Ile-Asp-aldehyde (Ac-VEID-CHO), selective for caspase-1 subfamily, caspase-3 subfamily and caspase-6, respectively, were loaded into the cells using an osmotic lysis of pinosomes method. Of these caspase inhibitors, only Ac-DEVD-CHO completely blocked morphological changes, caspase-3 subfamily protease activation and DNA ladder formation in H2O2-treated HL-60 cells. This inhibitory effect was dose-dependent. These results suggest that caspase-3, but not caspase-1 is required for commitment to ROS-triggered apoptosis. |
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Authors:
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T Matsura; M Kai; Y Fujii; H Ito; K Yamada |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Free radical research Volume: 30 ISSN: 1071-5762 ISO Abbreviation: Free Radic. Res. Publication Date: 1999 Jan |
Date Detail:
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Created Date: 1999-06-23 Completed Date: 1999-06-23 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9423872 Medline TA: Free Radic Res Country: SWITZERLAND |
Other Details:
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Languages: eng Pagination: 73-83 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Faculty of Medicine, Tottori University, Yonago, Japan. tmatsura@grape.med.tottori-u.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Chloromethyl Ketones
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administration & dosage,
pharmacology Apoptosis / drug effects* Blotting, Western Caspase 3 Caspases / antagonists & inhibitors, metabolism* Cell Nucleus / drug effects, metabolism DNA Fragmentation / drug effects Dose-Response Relationship, Drug Enzyme Activation / drug effects HL-60 Cells Humans Hydrogen Peroxide / pharmacology* Oligopeptides / administration & dosage, pharmacology Reactive Oxygen Species / metabolism Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Chloromethyl Ketones; 0/N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone; 0/Oligopeptides; 0/Reactive Oxygen Species; 0/acetyl-aspartyl-glutamyl-valyl-aspartal; 7722-84-1/Hydrogen Peroxide; EC 3.4.22.-/CASP3 protein, human; 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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