Alteration of p66shc is associated with endothelial dysfunction in the abdominal aortic coarctation of rats.
To examine the role of p66shc in endothelial dysfunction, we investigated the endothelium-dependent relaxation, protein expression and superoxide production in abdominal aortic coarctation rats. Endothelium-dependent relaxation to acetylcholine was impaired only in the aortic segments above the aortic coarctation (35.0+/-7.1% vs. 86.6+/-6.0% for sham control at 1 microM Ach). The aortic segments exposed to increased blood pressure showed a decreased phosphorylation of endothelial nitric oxide synthase, an increased phosphorylation of p66shc, and an increased superoxide production. Angiotensin II elicited a significantly increased phosphorylation of p66shc in the endothelial cells. Taken together, these findings suggest that the increased phosphorylation of p66shc is one of the important mediators in the impaired endothelium-dependent relaxation of aortic coarctation rats.
Lee
Sang Ki
SK
Infection Signaling Network Research Center, Research Institutes of Biomedical Sciences, Department of Physiology, College of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-gu, Daejeon, Republic of Korea.
Kim
Hyo Shin
HS
Song
Yun Jeong
YJ
Joo
Hee Kyoung
HK
Lee
Ji Young
JY
Lee
Kwon Ho
KH
Cho
Eun Jung
EJ
Cho
Chung-Hyun
CH
Park
Jin Bong
JB
Jeon
Byeong Hwa
BH
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000803:Angiotensin I / Q000494:pharmacology; D000818:Animals; D001017:Aortic Coarctation / Q000150:complications / Q000503:physiopathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D051379:Mice; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013481:Superoxides; D000803:Angiotensin I; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase