title: Insulin-like growth factor-1 receptor activation prevents hydrogen peroxide-induced oxidative stress, mitochondrial dysfunction and apoptosis.
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.
authors.affiliation: Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University, China.
authors.forename: Chang-Ning
authors.initials: CN
authors.lastname: Hao
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Geng
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.forename: Tong
authors.initials: T
authors.lastname: Yang
authors.forename: Ding-Feng
authors.initials: DF
authors.lastname: Su
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Duan
authors.forename: Yangxin
authors.initials: Y
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D045304:Cytochromes c / Q000032:analysis; D053938:DNA Fragmentation / Q000187:drug effects; D020868:Gene Silencing; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014652:Vascular Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D061945:Caspase Inhibitors; D034741:RNA, Small Interfering; D007334:Insulin-Like Growth Factor I; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D017526:Receptor, IGF Type 1; D053148:Caspase 3