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

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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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Acknowledgments

This work was supported by American Heart Association (0765149Y to Y Li), MacDonald Foundation (10RDM009 and 07RDM008 to Y Li), grants from Shanghai Institute of Technical Physics, Chinese Academy of Sciences, Shanghai, China (09JC1411100) and the National Basic Research Program of China (973 Program, 2009CB521901).

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Authors and Affiliations

  1. Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, 200092, China

    Chang-Ning Hao & Jun-Li Duan

  2. Texas Heart Institute, The University of Texas Medical School, 6770 Bertner Avenue, Houston, TX, 77030, USA

    Yong-Jian Geng & Yangxin Li

  3. Department of Pharmacology, Second Military Medical University, Shanghai, 200433, China

    Ding-Feng Su

  4. School of Basic Medical Science, Jilin University, Changchun, 13001, Jilin, China

    Fan Li & Tong Yang

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  1. Chang-Ning Hao
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  2. Yong-Jian Geng
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  3. Fan Li
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  4. Tong Yang
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  5. Ding-Feng Su
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  6. Jun-Li Duan
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  7. Yangxin Li
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Correspondence to Yangxin Li.

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The last three authors contributed equally to this work.

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Hao, CN., Geng, YJ., Li, F. et al. Insulin-like growth factor-1 receptor activation prevents hydrogen peroxide-induced oxidative stress, mitochondrial dysfunction and apoptosis. Apoptosis 16, 1118–1127 (2011). https://doi.org/10.1007/s10495-011-0634-9

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  • DOI: https://doi.org/10.1007/s10495-011-0634-9

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