Document Detail

Ethanol induces mouse spermatogenic cell apoptosis in vivo through over-expression of Fas/Fas-L, p53, and caspase-3 along with cytochrome c translocation and glutathione depletion.
MedLine Citation:
PMID:  20803734     Owner:  NLM     Status:  MEDLINE    
Although it has been well established that spermatogenic cells undergo apoptosis when treated with ethanol, the molecular mechanisms behind it remain to be investigated. Adult male mice were given intra-peritoneal injection (IP) of ethanol at a dose of 3 g (15%, v/v) per kg body weight per day during the period of 14 days. Testicular androgenesis and apoptotic germ cell death, along with different interrelated proteins expression, were evaluated. Ethanol treatment induced apoptotic spermatogenic cell death with a decrease in the plasma and intra-testicular testosterone concentration. Western blot analysis revealed that repeated ethanol treatment decreased the expression of steroidogenic acute regulatory protein (StAR), 3 beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17 beta-hydroxysteroid dehydrogenase (17beta-HSD); increased the expression of active caspase-3, p53, Fas and Fas-L; and led to up-regulation of Bax/Bcl-2 ratio and translocation of cytochrome c from mitochondria to cytosol in testis. It has also been shown in our study that repeated ethanol treatment led to up-regulation of caspase-3, p53, Fas, Fas-L transcripts; increase in caspase-3 and caspase-8 activities; diminution of 3beta-HSD, 17beta-HSD, and GPx activities; decrease in the mitochondrial membrane potential along with ROS generation and depletion of glutathione pool in the testicular tissue. The present study has indicated that the ethanol treatment induced apoptosis in the mouse testis through the increased expression of Fas/Fas-L and p53, up-regulation of Bax/Bcl-2 ratio, cytosolic translocation of cytochrome c along with caspase-3 activation and glutathione depletion.
Kuladip Jana; Narayan Jana; Dipak Kumar De; Sujoy Kumar Guha
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular reproduction and development     Volume:  77     ISSN:  1098-2795     ISO Abbreviation:  Mol. Reprod. Dev.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-30     Completed Date:  2010-12-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8903333     Medline TA:  Mol Reprod Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  820-33     Citation Subset:  IM    
Copyright Information:
(c) 2010 Wiley-Liss, Inc.
Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India.
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MeSH Terms
17-Hydroxysteroid Dehydrogenases / analysis
3-Hydroxysteroid Dehydrogenases / analysis
Caspase 3 / analysis
Cytochromes c / analysis
Ethanol / pharmacology*
Fas Ligand Protein / analysis
Glutathione / analysis
Membrane Potential, Mitochondrial / drug effects
Phosphoproteins / analysis
Proto-Oncogene Proteins c-bcl-2 / analysis
Reactive Oxygen Species / analysis
Spermatogenesis / drug effects*
Spermatozoa / cytology,  drug effects*,  physiology
Testis / drug effects*,  metabolism
Testosterone / biosynthesis,  blood
Tumor Suppressor Protein p53 / analysis
bcl-2-Associated X Protein / analysis
Reg. No./Substance:
0/Fas Ligand Protein; 0/Phosphoproteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Reactive Oxygen Species; 0/Tumor Suppressor Protein p53; 0/bcl-2-Associated X Protein; 0/steroidogenic acute regulatory protein; 58-22-0/Testosterone; 64-17-5/Ethanol; 70-18-8/Glutathione; 9007-43-6/Cytochromes c; EC 1.1.-/17-Hydroxysteroid Dehydrogenases; EC 1.1.-/3-Hydroxysteroid Dehydrogenases; EC 3.4.22.-/Caspase 3

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