Document Detail

Cytotoxicity of some oxysterols on human vascular smooth muscle cells was mediated by apoptosis.
MedLine Citation:
PMID:  9638517     Owner:  NLM     Status:  MEDLINE    
A decrease in smooth muscle cells is observed in advanced atherosclerotic lesion. To understand this mechanism, we selected oxysterols as candidates for toxic lipid, and examined their cytotoxicity on human cultured vascular smooth muscle cells, together with the manner of cell death. In the presence of 7-ketocholesterol or 7 beta-hydroxycholesterol (50 mumol/L), the percentage of detached cells increased significantly with dose dependency, and an increase in detached cell number and DNA nick detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling study (TUNEL) preceded an increase in lactate dehydrogenase released into the medium. DNA extracted from smooth muscle cells incubated with 7-ketocholesterol or 7 beta-hydroxycholesterol showed a laddering pattern on agarose electrophoresis. In the presence of 7-ketocholesterol or 7 beta-hydroxycholesterol, fragmented DNA quantified by the quantitative sandwich enzyme immunoassay was significantly increased. From these results, it is proposed that 7-ketocholesterol and 7 beta-hydroxycholesterol are toxic to smooth muscle cells, and that this cytotoxicity is mediated by apoptosis.
Y Miyashita; K Shirai; Y Ito; J Watanabe; Y Urano; T Murano; H Tomioka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of atherosclerosis and thrombosis     Volume:  4     ISSN:  1340-3478     ISO Abbreviation:  J. Atheroscler. Thromb.     Publication Date:  1997  
Date Detail:
Created Date:  1998-09-08     Completed Date:  1998-09-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9506298     Medline TA:  J Atheroscler Thromb     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  73-8     Citation Subset:  IM    
Sakura Hospital, Toho University School of Medicine, Chiba, Japan.
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MeSH Terms
Apoptosis / drug effects*
Cell Adhesion / drug effects
Cell Count / drug effects
Cell Survival / drug effects
Cholesterol / pharmacology
DNA Damage
DNA Fragmentation
Hydroxycholesterols / toxicity*
Ketocholesterols / toxicity*
L-Lactate Dehydrogenase / metabolism
Muscle, Smooth, Vascular / drug effects*,  metabolism
Reg. No./Substance:
0/Hydroxycholesterols; 0/Ketocholesterols; 566-26-7/cholest-5-en-3 beta,7 alpha-diol; 566-28-9/7-ketocholesterol; 57-88-5/Cholesterol; EC Dehydrogenase

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