{"title":"尽管 HIF-1α 发生了多 Q/E 插入突变,但南极鱼类 Notothenia coriiceps 的缺氧反应途径仍能发挥作用","authors":"K.M. O'Brien , A.S. Rix , A. Jasmin , E. Lavelle","doi":"10.1016/j.cbd.2024.101218","DOIUrl":null,"url":null,"abstract":"<div><p>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 <em>Notothenia coriiceps</em>, with a poly Q/E insertion mutation in HIF-1α that is 9 amino acids long, to hypoxia (2.3 mg L<sup>−1</sup> O<sub>2</sub>) or normoxia (10 mg L <sup>−1</sup> O<sub>2</sub>) 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 <em>N. coriiceps</em>. 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 <em>N. coriiceps</em> despite a poly Q/E mutation in HIF-1α, and confirm that Antarctic fishes are capable of altering gene expression in response to hypoxia.</p></div>","PeriodicalId":55235,"journal":{"name":"Comparative Biochemistry and Physiology D-Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The hypoxia response pathway in the Antarctic fish Notothenia coriiceps is functional despite a poly Q/E insertion mutation in HIF-1α\",\"authors\":\"K.M. O'Brien , A.S. Rix , A. Jasmin , E. Lavelle\",\"doi\":\"10.1016/j.cbd.2024.101218\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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 <em>Notothenia coriiceps</em>, with a poly Q/E insertion mutation in HIF-1α that is 9 amino acids long, to hypoxia (2.3 mg L<sup>−1</sup> O<sub>2</sub>) or normoxia (10 mg L <sup>−1</sup> O<sub>2</sub>) 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 <em>N. coriiceps</em>. 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 <em>N. coriiceps</em> despite a poly Q/E mutation in HIF-1α, and confirm that Antarctic fishes are capable of altering gene expression in response to hypoxia.</p></div>\",\"PeriodicalId\":55235,\"journal\":{\"name\":\"Comparative Biochemistry and Physiology D-Genomics & Proteomics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2024-02-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Comparative Biochemistry and Physiology D-Genomics & Proteomics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1744117X24000315\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Comparative Biochemistry and Physiology D-Genomics & Proteomics","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1744117X24000315","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
The hypoxia response pathway in the Antarctic fish Notothenia coriiceps is functional despite a poly Q/E insertion mutation in HIF-1α
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−1 O2) or normoxia (10 mg L −1 O2) 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.
期刊介绍:
Comparative Biochemistry & Physiology (CBP) publishes papers in comparative, environmental and evolutionary physiology.
Part D: Genomics and Proteomics (CBPD), focuses on “omics” approaches to physiology, including comparative and functional genomics, metagenomics, transcriptomics, proteomics, metabolomics, and lipidomics. Most studies employ “omics” and/or system biology to test specific hypotheses about molecular and biochemical mechanisms underlying physiological responses to the environment. We encourage papers that address fundamental questions in comparative physiology and biochemistry rather than studies with a focus that is purely technical, methodological or descriptive in nature.