Insulin-like growth factor-1 receptor activation prevents hydrogen peroxide-induced oxidative stress,mitochondrial dysfunction and apoptosis |
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Authors: | Chang-Ning Hao Yong-Jian Geng Fan Li Tong Yang Ding-Feng Su Jun-Li Duan Yangxin Li |
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Institution: | (1) Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, 200092, China;(2) Texas Heart Institute, The University of Texas Medical School, 6770 Bertner Avenue, Houston, TX 77030, USA;(3) Department of Pharmacology, Second Military Medical University, Shanghai, 200433, China;(4) School of Basic Medical Science, Jilin University, Changchun, 13001, Jilin, China; |
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Abstract: | 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. |
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