Adiponectin导致的内皮细胞的硝酸氧化物Synth.docVIP

Adiponectin-Induced Endothelial Nitric Oxide Synthase Activation and Nitric Oxide Production Are Mediated by APPL1 in Endothelial Cells Kenneth K.Y. Cheng1,2, Karen S.L. Lam1,2, Yu Wang3, Yu Huang4, David Carling5, Donghai Wu6, Chiwai Wong6, and Aimin Xu1,2,6 1 Department of Medicine, University of Hong Kong, Hong Kong, China2 Research Center of Heart, Brain Hormone and Healthy Aging, University of Hong Kong, Hong Kong, China3 Genome Research Center and Department of Biochemistry, University of Hong Kong, Hong Kong, China4 Department of Physiology, Chinese University of Hong Kong, Hong Kong, China5 Cellular Stress Group, Medical Research Council (MRC) Clinical Sciences Centre, Imperial College, U.K6 Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China Address correspondence and reprint requests to Aimin Xu, PhD, Department of Medicine, University of Hong Kong, L8-43, New Laboratory Block, 21 Sassoon Road, Hong Kong. E-mail: amxu@hkucc.hku.hk Abbreviations: AMPK, AMP-activated protein kinase; eNOS, endothelial nitric oxide synthase; GFP, green fluorescent protein; HSP, heat shock protein; HUVEC, human umbilical vein endothelial cell; L-NAME, N-nitro-L-arginine methyl ester; PI, phosphoinositide; RNAi, RNA interference  ?? ABSTRACT TOPABSTRACT RESEARCH DESIGN AND METHODS RESULTS DISCUSSION REFERENCES ?Adiponectin protects the vascular system partly through stimulation of endothelial nitric oxide (NO) production and endothelium-dependent vasodilation. The current study investigated the role of two recently identified adiponectin receptors, AdipoR1 and -R2, and their downstream effectors in mediating the endothelium actions of adiponectin. In human umbilical vein endothelial cells, adiponectin-induced phosphorylation of endothelial NO synthase (eNOS) at Ser1177 and NO production were abrogated when expression of AdipoR1 and -R2 were simultaneously suppressed. Proteomic analysis demonstrated that the cytop