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Effect of hypoxia mimetic cobalt chloride on the expression of extracellular-superoxide dismutase in retinal pericytes.
MedLine Citation:
PMID:  21804221     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The initial clinical stage of diabetic retinopathy (DR) is characterized by the development of intraretinal microvascular abnormalities. The increased formation of reactive oxygen species (ROS) is thought to be a key event in the pathogenesis of DR. Extracellular-superoxide dismutase (EC-SOD) is an anti-inflammatory enzyme that is distributed mainly in vascular cells and protects cells from ROS by scavenging superoxide anion. Treatment with cobalt chloride (CoCl(2)) decreased the expression of EC-SOD but not other SOD isozymes in pericytes accompanied with an increase of intracellular ROS production. Pre-treatment with N-acetylcysteine (NAC) significantly suppressed the ROS production and down-regulation of EC-SOD. We observed the activation of caspase-3 and DNA fragmentation as signs of apoptotic process by CoCl(2) treatment. In addition, these phenomena were significantly inhibited by pre-treatment with NAC. EC-SOD enhancer 4-phenyl butyric acid also suppressed the caspase-3 activation. It is known that the presence of a high level of EC-SOD throughout the vessel walls might have an important protective role against superoxide in the vascular system. The decrease in EC-SOD expression accompanied with elevation of ROS level in pericytes under hypoxia might induce and/or promote the ROS-triggered apoptosis of pericytes and the development of pathogenesis in DR.
Authors:
Tetsuo Adachi; Kazunari Aida; Hiroko Nishihara; Tetsuro Kamiya; Hirokazu Hara
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  34     ISSN:  1347-5215     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  2011  
Date Detail:
Created Date:  2011-08-01     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  1297-300     Citation Subset:  IM    
Affiliation:
Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University.
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