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Vascular endothelial growth factor as an autocrine survival factor for retinal pigment epithelial cells under oxidative stress via the VEGF-R2/PI3K/Akt.

Authors
 Suk Ho Byeon  ;  Sung Chul Lee  ;  Soo Hyun Choi  ;  Hyung-Keun Lee  ;  Joon H. Lee  ;  Young Kwang Chu  ;  Oh Woong Kwon 
Citation
 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol.51(2) : 1190-1197, 2010 
Journal Title
 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 
ISSN
 0146-0404 
Issue Date
2010
MeSH
Apoptosis ; Autocrine Communication/physiology* ; Blotting, Western ; Cell Culture Techniques ; Cell Survival ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Fluorescent Antibody Technique, Indirect ; Humans ; Hydrogen Peroxide/toxicity ; Oncogene Protein v-akt/metabolism ; Oxidative Stress* ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Retinal Pigment Epithelium/drug effects* ; Retinal Pigment Epithelium/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A/metabolism* ; Vascular Endothelial Growth Factor Receptor-1/metabolism ; Vascular Endothelial Growth Factor Receptor-2/metabolism
Abstract
PURPOSE: Vascular endothelial cell growth factor (VEGF) is strongly induced by oxidative stress in retinal pigment epithelial (RPE) cells, and VEGF-A is a survival factor for various cell types. This study was conducted to determine whether the autocrine VEGF signaling pathway in RPE cells is involved in the mechanism of adaptive response to oxidative stress. METHODS: ARPE-19 cells were treated with hydrogen peroxide, and cell death was measured by flow cytometry with annexin V-fluorescein isothiocyanate. Survival analysis was performed with pretreatment of VEGF-A-neutralizing antibodies, VEGF receptor tyrosine kinase inhibitor (SU5416), or VEGF-A receptor-neutralizing antibodies (anti-VEGF-R1 and anti-VEGF-R2). The expression of VEGF-A, -R1, -R2, and soluble VEGF-R1 was determined by semiquantitative RT-PCR or Western blot analysis. Phosphorylation of VEGF-R2 was detected with immunoprecipitation and immunoblot analysis. RESULTS: Hydrogen peroxide-induced cell death was promoted by pretreatment with VEGF-A and anti-VEGF-R2-neutralizing antibodies, but not with anti-VEGF-R1-neutralizing antibody. Phosphorylation of VEGF-R2 in RPE cells was induced by hydrogen peroxide, and pretreatment with anti-VEGF-A-neutralizing antibody inhibited phosphorylation. Phosphorylation of Akt under oxidative stress was abrogated by pretreatment with neutralizing antibodies against either VEGF-A or SU5416. CONCLUSIONS: Autocrine VEGF-A enhanced RPE cell survival under oxidative stress; the autocrine VEGF-A/VEGF-R2/PI3K/Akt pathway is involved. Neutralization of VEGF-A signaling, as in eyes with age-related macular degeneration, may influence RPE cell survival.
Files in This Item:
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Oh Woong(권오웅)
Byeon, Suk Ho(변석호) ORCID logo https://orcid.org/0000-0001-8101-0830
Lee, Sung Chul(이성철) ORCID logo https://orcid.org/0000-0001-9438-2385
Lee, Joon Haeng(이준행)
Lee, Hyung Keun(이형근) ORCID logo https://orcid.org/0000-0002-1123-2136
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/100476
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