Document Detail


Dihydrotestosterone protects human vascular endothelial cells from H(2)O(2)-induced apoptosis through inhibition of caspase-3, caspase-9 and p38 MAPK.
MedLine Citation:
PMID:  20599910     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Zhe-rong Xu; Lin Hu; Lin-fang Cheng; Yun Qian; Yun-mei Yang
Publication Detail:
Type:  Journal Article     Date:  2010-07-01
Journal Detail:
Title:  European journal of pharmacology     Volume:  643     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-02     Completed Date:  2010-12-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  254-9     Citation Subset:  IM    
Copyright Information:
2010 Elsevier B.V. All rights reserved.
Affiliation:
Department of Geriatrics, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
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MeSH Terms
Descriptor/Qualifier:
Androgens / 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:
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

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