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Title: Thiol regulation of vascular endothelial growth factor-A and its receptors in human retinal pigment epithelial cells. Author: Sreekumar PG, Kannan R, de Silva AT, Burton R, Ryan SJ, Hinton DR. Journal: Biochem Biophys Res Commun; 2006 Aug 11; 346(4):1200-6. PubMed ID: 16793007. Abstract: We investigated the secretion and expression of VEGF-A and its receptors in human retinal pigment epithelial cells (RPE) under conditions of oxidative stress induced by glutathione (GSH) depletion. RPE cells were treated with 500 microM DL-buthionine-(S,R)-sulfoximine (BSO) for varying times up to 24 h. Cellular GSH levels, GSH:GSSG ratios, VEGF-A mRNA and protein expression, as well as VEGF-A secretion, and VEGFR-1 and VEGFR-2 receptor expression were determined. Treatment with BSO caused a significant decrease in intracellular GSH and in GSH/GSSG ratios. Treatment with BSO increased VEGF-A mRNA linearly with time which was significant at 24h (p<0.01 vs untreated controls). An increase was also found for VEGF-A secretion with BSO treatment; incubation of RPE with GSH monoethyl ester (GSH-MEE) caused an 84% decrease in VEGF-A secretion. Further, thiol depletion by BSO caused a significant induction of VEGFR-1 and VEGFR-2. Thus, our studies show that cellular redox status plays an important role in VEGF regulation in RPE cells.[Abstract] [Full Text] [Related] [New Search]