Intracellular Ca2+ can compensate for the lack of NADPH oxidase-derived ROS in endothelial cells.
The aim of the present study is to determine the role of intracellular Ca(2+) in VEGF signaling. We demonstrate that reduction in Ca(2+) by chelating compound BAPTA-AM or by IP(3)-endoplasmic reticulum blocker 2-APB selectively inhibited VEGF-induced activation of c-Src-PI3K-Akt but not ERK1/2 in human coronary artery endothelial cells (HCAEC). We also show that the selective inhibitory effects of NADPH oxidase knockdown on VEGF-mediated activation of c-Src-PI3K-Akt signaling and cell proliferation in HCAEC can be reversed by increase in intracellular Ca(2+). These results suggest an essential role for Ca(2+) in redox-dependent selective activation of c-Src-PI3K-Akt and endothelial cell proliferation.
Lee
Monica
M
The Center for Vascular Biology Research, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Spokes
Katherine C
KC
Aird
William C
WC
Abid
Md Ruhul
MR
D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D003331:Coronary Vessels / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives; D004721:Endoplasmic Reticulum / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D007477:Ions / Q000378:metabolism / Q000494:pharmacology; D019255:NADPH Oxidases / Q000378:metabolism* / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III; D010084:Oxidation-Reduction; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000494:pharmacology; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000502:physiology; D045162:Thiazolidinediones; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism / Q000494:pharmacology
D007477:Ions; D017382:Reactive Oxygen Species; D045162:Thiazolidinediones; D042442:Vascular Endothelial Growth Factors; D000077154:Rosiglitazone; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; D051057:Proto-Oncogene Proteins c-akt; D002118:Calcium