Insulin-like growth factor binding protein-1 regulates HIF-1α degradation to inhibit apoptosis in hypoxic cardiomyocytes

胰岛素样生长因子结合蛋白-1调控HIF-1α降解抑制缺氧心肌细胞凋亡

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作者:Xiaoyan Tang, Huilin Jiang, Peiyi Lin, Zhenhui Zhang, Meiting Chen, Yi Zhang, Junrong Mo, Yongcheng Zhu, Ningning Liu, Xiaohui Chen

Abstract

Hypoxia is important in ischemic heart disease. Excessive Insulin-like growth factor binding protein-1 (IGFBP-1) amounts are considered to harm cardiomyocytes in acute myocardial infarction. However, the mechanisms by which IGFBP-1 affects cardiomyocytes remain undefined. The present study demonstrated that hypoxia up-regulates IGFBP-1 and HIF-1α protein expression in cardiomyocytes. Subsequent assays showed that IGFBP-1 suppression decreased HIF-1α expression and inhibited hypoxia-induced apoptosis in cardiomyocytes, which was reversed by HIF-1α overexpression, indicating that HIF-1α is essential to IGFBP-1 function in cellular apoptosis. In addition, we showed that IGFBP-1 regulated HIF-1α stabilization through interacting with VHL. The present findings suggest that IGFBP-1-HIF-1α could be targeted for treating ischemic heart disease.

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