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Globular adiponectin protects human umbilical vein endothelial cells against apoptosis through adiponectin receptor 1/adenosine monophosphate-activated protein kinase pathway

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Zhao Hongyu 1   Zhao Min 1   Yi Tongning 2   Zhang Jin 3 *  
文摘 Background Endothelial dysfunction is a key event in the onset and progression of atherosclerosis in diabetic patients. Apoptosis may lead to endothelial dysfunction and contribute to vascular complications. However, no study has addressed apoptosis in human umbilical vein endothelial cells (HUVECs) induced by an intermittent high-glucose media and its association with adiponectin receptor 1 (adipoR1), adipoR2, or adenosine monophosphate (AMP)-activated protein kinase (AMPK). Methods HUVECs were cultured in continuous normal glucose (5.5 mmol/L), continuous high glucose (25 mmol/L), alternating normal and high glucose and mannitol. In the alternating normal and high-glucose media, HUVECs were treated under different conditions. First, cells were transfected with the adipoRl-specific small-interfering RNA (siRNA) and then stimulated with globular adiponectin (gAD). Second, cells were cultured in both gAD and the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR). Third, cells were cultured in the AMPK inhibitor adenine-9-β-D-arabino-furanoside (araA), gAD, and in AICAR. Results HUVEC apoptosis increased more significantly in an intermittent high-glucose medium than in a constant high-glucose medium. HUVEC apoptosis induced by an intermittent high-glucose medium was inhibited when the cells were pretreated with 3 μg/ml gAD, which rapidly activated AMPK and adipoR1 in HUVECs. However, adipoR2 was not activated. Conclusions We found that adipoR1, not adipoR2, is involved in mediating intermittent high-concentration glucoseevoked apoptosis in endothelial cells. gAD activated AMPK through adipoR1, leads to the partial inhibition of HUVEC apoptosis. A fluctuating glucose medium is more harmful than a constant high-glucose medium to endothelial cells.
来源 Chinese Medical Journal ,2011,124(16):2540-2547 【核心库】
DOI 10.3760/cma.j.issn.0366-6999.2011.16.026
关键词 globular adiponectin ; adiponectin receptor 1 ; AMP-activated protein kinase ; apoptosis ; intermittent glucose
地址

1. Department of Emergency, Shengjing Hospital, China Medical University, Liaoning, Shenyang, 110004  

2. Department of Endocrinology, First Hospital of Liaoning University of Traditional Chinese Medicine, Liaoning, Shenyang, 110032  

3. Department of Endocrinology, First Hospital of China Medical University, Liaoning, Shenyang, 110001

语种 英文
文献类型 研究性论文
ISSN 0366-6999
学科 中国医学
文献收藏号 CSCD:4325356

参考文献 共 37 共2页

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