University of Alaska Fairbanks, Institute of Arctic Biology and Department of Biology & Wildlife, Fairbanks, AK 99775, USA.
University of Alaska Fairbanks, Institute of Arctic Biology and Department of Biology & Wildlife, Fairbanks, AK 99775, USA.
Comp Biochem Physiol Part D Genomics Proteomics. 2024 Jun;50:101218. doi: 10.1016/j.cbd.2024.101218. Epub 2024 Feb 18.
Antarctic notothenioid fishes, inhabiting the oxygen-rich Southern Ocean, possess a polyglutamine and glutamic acid (poly Q/E) insertion mutation in the master transcriptional regulator of oxygen homeostasis, hypoxia- inducible factor-1α (HIF-1α). To determine if this mutation impairs the ability of HIF-1 to regulate gene expression in response to hypoxia, we exposed Notothenia coriiceps, with a poly Q/E insertion mutation in HIF-1α that is 9 amino acids long, to hypoxia (2.3 mg L O) or normoxia (10 mg L O) for 12 h. Heart ventricles, brain, liver, and gill tissue were harvested and changes in gene expression quantified using RNA sequencing. Levels of glycogen and lactate were also quantified to determine if anaerobic metabolism increases in response to hypoxia. Exposure to hypoxia resulted in 818 unique differentially expressed genes (DEGs) in liver tissue of N. coriiceps. Many hypoxic genes were induced, including ones involved in the MAP kinase and FoxO pathways, glycolytic metabolism, and vascular remodeling. In contrast, there were fewer than 104 unique DEGs in each of the other tissues sampled. Lactate levels significantly increased in liver in response to hypoxia, indicating that anaerobic metabolism increases in response to hypoxia in this tissue. Overall, our results indicate that the hypoxia response pathway is functional in N. coriiceps despite a poly Q/E mutation in HIF-1α, and confirm that Antarctic fishes are capable of altering gene expression in response to hypoxia.
南极鳕鱼生活在富含氧气的南大洋中，其氧稳态主转录调节剂缺氧诱导因子-1α（HIF-1α）中存在多聚谷氨酰胺和谷氨酸（多 Q/E）插入突变。为了确定这种突变是否会损害 HIF-1 调节基因表达对缺氧的反应能力，我们将携带 HIF-1α中 9 个氨基酸长的多 Q/E 插入突变的 Notothenia coriiceps 暴露于缺氧（2.3 mg L O）或常氧（10 mg L O）下 12 小时。采集心脏心室、大脑、肝脏和鳃组织，并使用 RNA 测序定量基因表达的变化。还定量了糖原和乳酸的水平，以确定无氧代谢是否会因缺氧而增加。缺氧暴露导致 N. coriiceps 肝脏组织中出现 818 个独特的差异表达基因（DEGs）。许多缺氧诱导基因被诱导，包括参与 MAP 激酶和 FoxO 途径、糖酵解代谢和血管重塑的基因。相比之下，在其他采样组织中，每个组织中少于 104 个独特的 DEGs。肝脏中乳酸水平因缺氧而显著升高，表明该组织中无氧代谢因缺氧而增加。总的来说，我们的结果表明，尽管 HIF-1α 中存在多 Q/E 突变，但南极鳕鱼的缺氧反应途径是功能性的，并证实南极鱼类能够改变基因表达以应对缺氧。
