Document Detail

Bcl-2 overexpression increases survival in human retinal pigment epithelial cells exposed to H(2)O(2).
MedLine Citation:
PMID:  12126940     Owner:  NLM     Status:  MEDLINE    
The integrity of the retinal pigment epithelium, especially that of the macula is essential for the preservation of vision into old age. The chronic exposure to sunlight and peroxidized lipids from phagocytized photoreceptor outer segments imposes a high level of oxidative stress on the retinal tissues, which increases with age as antioxidant protection declines and therefore could accelerate apoptosis. Bcl-2 known to facilitate mitochondrial DNA repair and cellular survival in other tissues was overexpressed in a single clone of human retinal pigment epithelium cells after stable transfection with humanbcl-2 in rhoSFV-neoexpression factor. Near confluent cells (2nd-4th generation permanently bcl-2 transfected) were protected from mitochondrial dysfunction after exposure to H(2)O(2) up to 150 microM. With 200 microM H(2)O(2), function in transfected cells declined by only 25% control activity as determined by MTT reduction assays, compared to wild type and vector only transfected cells expressing normal bcl-2 levels. Similarly the bcl-2 -transfected cells were more resistant to mitochondrial DNA damage after H(2)O(2) treatment than the other groups and suffered 50% less damage after exposure to 200 microM H(2)O(2), as assayed by quantitative polymerase chain reaction assays. These data suggest that bcl-2 overexpression protects human RPE cells from mitochondrial respiratory dysfuction, mitochondrial DNA damage and promotes cellular survival in response to oxidative stress induced by H(2)O(2).
Bernard F Godley; Gui-Fang Jin; Yan-Shi Guo; John S Hurst
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Experimental eye research     Volume:  74     ISSN:  0014-4835     ISO Abbreviation:  Exp. Eye Res.     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-07-19     Completed Date:  2002-10-17     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370707     Medline TA:  Exp Eye Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  663-9     Citation Subset:  IM    
Retina Foundation of the Southwest, Dallas, TX 75321, USA.
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MeSH Terms
Blotting, Western
Cell Culture Techniques
Cell Survival / drug effects,  physiology
DNA Damage
DNA, Mitochondrial / genetics
Dose-Response Relationship, Drug
Genes, bcl-2
Hydrogen Peroxide / pharmacology*
Mitochondria / drug effects,  metabolism
Oxidative Stress / physiology
Pigment Epithelium of Eye / cytology,  drug effects,  metabolism*
Proto-Oncogene Proteins c-bcl-2 / physiology*
Grant Support
EY 12850-01/EY/NEI NIH HHS
Reg. No./Substance:
0/DNA, Mitochondrial; 0/Proto-Oncogene Proteins c-bcl-2; 7722-84-1/Hydrogen Peroxide

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