Insulin-like growth factor-1 receptor activation prevents hydrogen peroxide-induced oxidative stress, mitochondrial dysfunction and apoptosis

被引:45
作者
Hao, Chang-Ning [2 ]
Geng, Yong-Jian [1 ]
Li, Fan [3 ]
Yang, Tong [3 ]
Su, Ding-Feng [4 ]
Duan, Jun-Li [2 ]
Li, Yangxin [1 ]
机构
[1] Univ Texas Houston, Texas Heart Inst, Sch Med, Houston, TX 77030 USA
[2] Shanghai Jiao Tong Univ, Dept Gerontol, Xinhua Hosp, Shanghai 200092, Peoples R China
[3] Jilin Univ, Sch Basic Med Sci, Changchun 13001, Jilin, Peoples R China
[4] Second Mil Med Univ, Dept Pharmacol, Shanghai 200433, Peoples R China
关键词
Oxidative stress; Apoptosis; IGF-1; Mitochondria; Cytochrome-c; Caspase-3; CYTOCHROME-C RELEASE; HIGH GLUCOSE; ENDOTHELIAL-CELLS; NADPH OXIDASE; PC12; CELLS; EXPRESSION; ACID; MECHANISMS; EVENT; DEATH;
D O I
10.1007/s10495-011-0634-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Vascular disease is the leading cause of morbidity and mortality. Oxidative stress can cause endothelial cell apoptosis. Low insulin like growth factor-1 (IGF-1) has been linked to adverse risk profile and increased vascular disease incidence. Since IGF-1 acts as an important survival factor for multiple cell types, we undertook this study to investigate whether IGF-1 favorably affects oxidative-stress mediated apoptosis of vascular endothelial cells. Exposure to hydrogen peroxide induced apoptotic changes (e. g. DNA fragmentation, altered mitochondrial membrane potential and caspase-3 activity) in human umbilical vein endothelial cells (HUVECs) in a time dependent manner. Addition of IGF-1 blocked the oxidative-stress effect parallel to IGF-1 receptor (IGF-1R) expression, and silencing the IGF-1R with small interference RNA attenuated the IGF-1 influence. Our findings show that enhanced IGF-1 signaling inhibits oxidative-stress induced apoptosis in HUVECs by reducing mitochondrial dysfunction. Specifically the protective mechanism of IGF-1 involves preserving the mitochondrial membrane potential, maintaining the mitochondrial retention of cytochrome-c, and reducing caspase-3 activity. These results may have therapeutic implications in preventing/reducing vascular disease associated endothelial dysfunction.
引用
收藏
页码:1118 / 1127
页数:10
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