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

• Main Authors: Xiaoyan Tang, Huilin Jiang, Peiyi Lin, Zhenhui Zhang, Meiting Chen, Yi Zhang, Junrong Mo, Yongcheng Zhu, Ningning Liu, Xiaohui Chen
• Format: Article
• Language: English
• Published: Nature Publishing Group 2021-09-01
• Series: Cell Death Discovery
• Online Access: https://doi.org/10.1038/s41420-021-00629-3
• ISSN: 2058-7716

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.