Document Detail


Nitrite-modified extracellular matrix proteins deleteriously affect retinal pigment epithelial cell function and viability: a comparison study with nonenzymatic glycation mechanisms.
MedLine Citation:
PMID:  16109650     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Extracellular matrix (ECM) plays an important role in the regulation of cell function. The aging process may involve chemical modifications to ECM proteins, which may contribute to the aging of the Bruch membrane and pathogenesis of age-related macular degeneration (AMD). The purpose of this study is to investigate nitrite modification of basement membrane-like proteins on RPE cell behavior as a model for the aging of the Bruch membrane in age-related eye diseases. As a comparison, retinal pigment epithelium (RPE) cell behavior on glycolaldehyde-modified matrices (GMM) was also studied. METHODS: Growth factor reduced Matrigel was reacted with nitrite or glycolaldehyde for 1 week or 12 hr, respectively. Calf RPE cells were plated on the modified matrices and examined in several ways. Attachment rates, proliferation rates, apoptosis, and necrosis were determined. Cell morphology and cell susceptibility to A2E-mediated damage was also monitored. RESULTS: Nitrite-modified matrices (NMMs) inhibited cell attachment by 65% and proliferation by 33.7% compared to 69.6% and 21.7%, respectively, by GMM. Proliferation inhibition was not significant when cells were plated at high density on GMM (3.47%) but significant on NMM (20.9%). NMM induced cell apoptosis and necrosis, but GMM induced cell apoptosis only. Both modifications inhibited RPE differentiation. RPE cells on both matrices were more susceptible to blue light mediated damage by A2E, but damage was greater on NMM. CONCLUSIONS: NMM has significant damaging effects on RPE cell function and viability that is similar to the damaging effects of GMM. These studies may have relevance to the RPE dysfunction observed during the progression of AMD.
Authors:
Zhen Wang; David C Paik; Lucian V Del Priore; Robert L Burch; Elizabeth R Gaillard
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Current eye research     Volume:  30     ISSN:  0271-3683     ISO Abbreviation:  Curr. Eye Res.     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-08-19     Completed Date:  2005-10-20     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8104312     Medline TA:  Curr Eye Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  691-702     Citation Subset:  IM    
Affiliation:
Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, Illinois 60115, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Basement Membrane / drug effects
Cattle
Cell Adhesion
Cell Culture Techniques
Cell Proliferation
Cell Survival
Collagen
Drug Combinations
Extracellular Matrix Proteins / metabolism*
Glycosylation
Laminin
Necrosis
Nitrosation
Pigment Epithelium of Eye / cytology*,  drug effects*
Proteoglycans
Pyridinium Compounds / toxicity
Retinoids / toxicity
Sodium Nitrite / toxicity*
Grant Support
ID/Acronym/Agency:
K08 AG000863/AG/NIA NIH HHS; R01 EY12344/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/A2E compound; 0/Drug Combinations; 0/Extracellular Matrix Proteins; 0/Laminin; 0/Proteoglycans; 0/Pyridinium Compounds; 0/Retinoids; 119978-18-6/matrigel; 7632-00-0/Sodium Nitrite; 9007-34-5/Collagen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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