Tan Tianfeng, Yu Richard Man Kit, Wu Rudolf Shiu Sun, Kong Richard Yuen Chong
State Key Laboratory in Marine Pollution, City University of Hong Kong, Hong Kong SAR.
Shenzhen Key Laboratory for the Sustainable Use of Marine Biodiversity, Research Centre for the Oceans and Human Health, City University of Hong Kong Shenzhen Research Institute, Shenzhen, China.
Gene Regul Syst Bio. 2017 Jun 8;11:1177625017713193. doi: 10.1177/1177625017713193. eCollection 2017.
Hypoxia is an important environmental stressor leading to endocrine disruption and reproductive impairment in fish. Although the hypoxia-inducible factor 1 (HIF-1) is known to regulate the transcription of various genes mediating oxygen homeostasis, its role in modulating steroidogenesis-related gene expression remains poorly understood. In this study, the regulatory effect of HIF-1 on the expression of 9 steroidogenic enzyme genes was investigated in zebrafish embryos using a "gain-of-function and loss-of-function" approach. Eight of the genes, , and , were found to be differentially upregulated at 24 and 48 hpf following zHIF-1α-ΔODD overexpression (a mutant zebrafish HIF-1α protein with proline-414 and proline-557 deleted). Knockdown of zHIF-1α also affected the expression pattern of the steroidogenic enzyme genes. Overexpression of zHIF-1α and hypoxia exposure resulted in downregulated expression but upregulated and expression in zebrafish embryos. Conversely, the expression patterns of these 3 genes were reversed in embryos in which zHIF-1α was knocked down under normoxia, suggesting that these 3 genes are regulated by HIF-1. Overall, the findings from this study indicate that HIF-1-mediated mechanisms are likely involved in the regulation of specific steroidogenic genes.
缺氧是一种重要的环境应激源，可导致鱼类内分泌紊乱和生殖功能受损。尽管已知缺氧诱导因子1（HIF-1）可调节介导氧稳态的各种基因的转录，但其在调节类固醇生成相关基因表达中的作用仍知之甚少。在本研究中，使用“功能获得和功能丧失”方法，在斑马鱼胚胎中研究了HIF-1对9种类固醇生成酶基因表达的调节作用。在过表达zHIF-1α-ΔODD（一种缺失脯氨酸-414和脯氨酸-557的突变斑马鱼HIF-1α蛋白）后，在24和48 hpf时发现其中8个基因，即 、 和 ，有差异上调。敲低zHIF-1α也影响了类固醇生成酶基因的表达模式。过表达zHIF-1α和暴露于缺氧环境导致斑马鱼胚胎中 表达下调，但 和 表达上调。相反，在常氧条件下敲低zHIF-1α的胚胎中，这3个基因的表达模式发生了逆转，表明这3个基因受HIF-1调节。总体而言，本研究结果表明，HIF-1介导的机制可能参与特定类固醇生成基因的调节。
