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