Angiotensin II-induced apoptosis in human endothelial cells is inhibited by adiponectin through restoration of the association between endothelial nitric oxide synthase and heat shock protein 90.
Adiponectin can protect vessels from injury by promoting the activity of endothelial nitric oxide synthase (eNOS) with increased nitric oxide production. Recently, it was demonstrated that eNOS activity is highly regulated by heat shock protein 90 (HSP90). We tested the hypothesis that adiponectin can prevent endothelial cell injury produced by angiotensin II through promotion of the association between eNOS and HSP90. Cultured human umbilical vein endothelial cells (HUVECs) were treated with angiotensin II (2 microM) to induce apoptosis. In the presence of globular adiponectin, apoptosis was inhibited in a dose-response manner. Angiotensin II-induced apoptosis was also inhibited by treatment with an NO donor and by combined treatment with both angiotensin II type 1 and type 2 receptor blockers. Western blotting and immunoprecipitation of the lysates from the treated cells showed that globular adiponectin could restore the association between eNOS and HSP90 and enhance the phosphorylation of eNOS. In conclusion, angiotensin II-induced human endothelial cell apoptosis can be prevented by adiponectin through promotion and stabilization of the association between eNOS and HSP90.
Lin
Lian-Yu
LY
Division of Cardiology, Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, No. 7, Chun-Shan S. Rd, Taipei, Taiwan.
Lin
Chien-Yu
CY
Su
Ta-Chen
TC
Liau
Chiau-Suong
CS
D052242:Adiponectin; D000804:Angiotensin II / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D010766:Phosphorylation; D011506:Proteins / Q000502:physiology*
D052242:Adiponectin; D018841:HSP90 Heat-Shock Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D000804:Angiotensin II; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III