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The Hypoxia Response Pathway is Functional Despite a Mutation in HIF‐1α in the Antarctic Notothenioid Fish Notothenia coriiceps
Author(s) -
O'Brien Kristin,
Jasmin Ariane,
Schilkey Faye,
Sena Johnny,
Lavelle Evan
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.05035
Subject(s) - biology , hypoxia (environmental) , microbiology and biotechnology , glycolysis , glycogen , endocrinology , downregulation and upregulation , medicine , gene expression , gene , metabolism , biochemistry , oxygen , chemistry , organic chemistry
Antarctic notothenioid fishes have evolved in the icy‐cold and oxygen‐rich Southern Ocean, which may have reduced selective pressure to maintain a robust molecular response to hypoxia. Prior studies in Antarctic fishes have shown that the master transcriptional regulator of oxygen homeostasis, hypoxia‐ inducible factor‐1α (HIF‐1α), has a polyglutamine and glutamic acid insertion mutation that varies in length from 16 to 34 amino acids. Although HIF‐1α accumulates in the nucleus of cardiac myocytes of the Antarctic fish Notothenia coriiceps exposed to hypoxia, the expression of glycolytic genes is not induced. This study sought to better characterize the hypoxia response in N. coriiceps, a non‐model organism, by creating a pathway association pipeline to efficiently quantify changes in gene expression in heart ventricle, brain, liver, and gill tissues. RNA‐Seq was conducted in animals held at normoxia (10 mg L ‐1 O 2 ) or hypoxia (2 mg L ‐1 O 2 ) for 12 hours. Levels of glycogen and lactate were also quantified to determine if hypoxia induces a shift towards anaerobic metabolism. Despite an increase in HIF‐1α protein levels in heart ventricles of N. coriiceps in response to hypoxia, the expression of only 22 genes increased, none of which are known to be regulated by HIF‐1. Liver displayed the most robust molecular response to hypoxia with the expression of 664 genes significantly changing, including an upregulation of genes in the MAP kinase and FoxO pathways and ones involved in glycolytic metabolism and vascular remodeling. Consistent with this, levels of lactate significantly increased and glycogen levels tended to decrease ( P = 0.19) only in liver in response to hypoxia. Overall, the molecular response to hypoxia appears diminished in some tissues, but not absent, in Antarctic fishes.