| Dihydrotestosterone protects human vascular endothelial cells from H(2)O(2)-induced apoptosis through inhibition of caspase-3, caspase-9 and p38 MAPK. | |
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MedLine Citation:
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PMID: 20599910 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Oxidative stress is proved to be harmful to the vascular endothelial cells which are important in preventing the formation and progression of atheromatous plaque. This study was designed to investigate the protective effect and potential mechanisms of dihydrotestosterone (DHT) against H(2)O(2)-induced apoptosis of human umbilical vein endothelial cells (ECV-304). ECV-304 cells were pretreated with different concentrations of DHT (0.01, 0.1 and 1 microM) for 2h, followed by exposure to 100 microM H(2)O(2) for 18h. 3-(4,5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to evaluate cell viability. To detect apoptosis, the cells were assessed by morphologic examination and Annexin V-propidium iodide double staining with flow cytometry. Finally, the expression of caspase-3, caspase-9 and phospho p38 MAPK was assayed by Western blot to investigate the possible molecular mechanisms. We found that H(2)O(2) treatment for 18h significantly decrease the viability of ECV-304 cells characterized by a high percentage of apoptotic cells. DHT could antagonize the apoptosis inducing effect of H(2)O(2) in a dose-dependent manner. Consistently, DHT also significantly inhibit the expression of caspase-3, caspase-9 and phospho p38 MAPK induced by H(2)O(2). In summary, pretreatment with DHT can inhibit apoptosis of ECV-304 cells induced by H(2)O(2). The protective effect of DHT was associated with the inhibition of caspase-3, caspase-9 and phospho p38 MAPK expression. |
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Authors:
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Zhe-rong Xu; Lin Hu; Lin-fang Cheng; Yun Qian; Yun-mei Yang |
Publication Detail:
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Type: Journal Article Date: 2010-07-01 |
Journal Detail:
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Title: European journal of pharmacology Volume: 643 ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-02 Completed Date: 2010-12-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 254-9 Citation Subset: IM |
Copyright Information:
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2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Department of Geriatrics, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Androgens
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pharmacology Apoptosis / drug effects* Caspase 3 / metabolism Caspase 9 / metabolism Caspases / metabolism* Cell Line Cell Survival / drug effects Dihydrotestosterone / pharmacology* Down-Regulation / drug effects Endothelium, Vascular / drug effects*, enzymology, pathology Humans Hydrogen Peroxide / toxicity Mitochondria / drug effects Osmolar Concentration Oxidants / toxicity Oxidative Stress / drug effects* Phosphorylation / drug effects Plaque, Atherosclerotic / prevention & control Protective Agents / pharmacology* p38 Mitogen-Activated Protein Kinases / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Androgens; 0/Oxidants; 0/Protective Agents; 521-18-6/Dihydrotestosterone; 7722-84-1/Hydrogen Peroxide; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/CASP9 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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