| Arsenic trioxide-induced apoptosis in H9c2 cardiomyocytes: implications in cardiotoxicity. | |
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MedLine Citation:
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PMID: 18346055 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Arsenic trioxide (As(2)O(3)) achieved dramatic remissions in patients with acute promyelocytic leukaemia. Clinical reports have shown that treatment was associated with cardiotoxicity. We investigated the toxic mechanisms of As(2)O(3) in H9c2 cardiomyocytes. Clinically relevant concentrations of As(2)O(3) (2-10 microM) reduced the viability of H9c2 cells in a concentration-dependent manner. The decreased cell viability was because As(2)O(3) induced cell apoptosis (cell shrinkage, nuclear alterations and caspase-3 activation), or even necrosis at higher concentrations. Inhibition of caspase-3 with a specific inhibitor, Ac-DEVD-CHO, suppressed apoptosis induced by As(2)O(3). In addition, reactive oxygen species formation and cellular Ca(2+) overload were observed in H9c2 cells exposed to As(2)O(3), which was partly inhibited by vitamin E and verapamil. These results suggest that As(2)O(3)-induced cardiotoxicity is mediated, at least in part, by activation of caspase-3 pathway, which may be triggered by reactive oxygen species formation and intracellular Ca(2+) overload. |
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Authors:
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Xiaoyan Zhao; Tieming Feng; He Chen; Hongli Shan; Yong Zhang; Yanjie Lu; Baofeng Yang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-03-12 |
Journal Detail:
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Title: Basic & clinical pharmacology & toxicology Volume: 102 ISSN: 1742-7843 ISO Abbreviation: Basic Clin. Pharmacol. Toxicol. Publication Date: 2008 May |
Date Detail:
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Created Date: 2008-04-17 Completed Date: 2008-07-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101208422 Medline TA: Basic Clin Pharmacol Toxicol Country: Denmark |
Other Details:
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Languages: eng Pagination: 419-25 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Harbin Medical University, Harbin, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents / adverse effects* Antioxidants / pharmacology Apoptosis / drug effects* Arsenicals / adverse effects* Caspase 3 / metabolism Cell Line Cell Survival / drug effects Cysteine Proteinase Inhibitors / pharmacology Dose-Response Relationship, Drug Enzyme Activation Myocytes, Cardiac / cytology, drug effects*, metabolism Oligopeptides / pharmacology Oxidative Stress / drug effects Oxides / adverse effects* Rats Reactive Oxygen Species / metabolism Verapamil / pharmacology Vitamin E / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Antioxidants; 0/Arsenicals; 0/Cysteine Proteinase Inhibitors; 0/Oligopeptides; 0/Oxides; 0/Reactive Oxygen Species; 0/acetyl-aspartyl-glutamyl-valyl-aspartal; 1327-53-3/arsenic trioxide; 1406-18-4/Vitamin E; 52-53-9/Verapamil; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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