Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 387, Issue 3, Pages 461-466Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2009.07.038
Keywords
Diabetes; Endothelial cells; G-proteins; Retinopathy
Categories
Funding
- National Institutes of Health
- Juvenile Diabetes Research Foundation
- Thomas Foundation
- Research to Prevent Blindness
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H-Ras, a small molecular weight G-protein, undergoes post-translational modifications enabling its translocation from cytosol to the membrane. Hyperglycemia increases apoptosis of retinal capillary cells via activation of H-Ras, which can be ameliorated by farnesylation inhibitors. Our aim is to investigate the mechanism of retinal H-Ras activation in diabetes. H-Ras and Raf-1 were quantified in the retinal membrane and cytosol fractions obtained from streptozotocin-induced diabetes rats, and the role of posttranslation modification was determined by investigating the effect of simvastatin oil diabetes-induced alterations. The effect of H-Ras-siRNA on membrane translocation and apoptosis was also determined in bovine retinal endothelial cells (BRECs). Diabetes increased expressions of H-Ras and Raf-1 in the retinal membranes, and simvastatin prevented such trans location. Glucose-exposure of BRECs increased membrane H-Ras expression and H-Ras-siRNA prevented this translocation, and also decreased their apoptosis. Thus, membrane translocation of H-Ras is a plausible mechanism responsible for accelerated apoptosis of retinal capillary cells in diabetes. (C) 2009 Elsevier Inc. All rights reserved.
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