title: HIF signaling and overall gene expression changes during hypoxia and prolonged exercise differ considerably.
abstract: Exercise as well as hypoxia cause an increase in angiogenesis, changes in mitochondrial density and alterations in metabolism, but it is still under debate whether the hypoxia inducible factor (HIF) is active during both situations. In this study gene expression analysis of zebrafish larvae that were raised under normoxic, hypoxic, or training conditions were compared, using microarray analysis, quantitative real-time PCR and protein data. Although HIF expression is posttranslationally regulated, mRNA expression levels of all three isoforms (HIF-1α, HIF-2α, and HIF-3α) differed in each of the experimental groups, but the changes observed in hypoxic animals were much smaller than in trained larvae. Prominent changes were seen for Hif-2α expression, which significantly increased after the first day of exercise and then decreased down to values significantly below control values. HIF-3α mRNA expression in turn increased significantly, and at the end of the training period (9-15 days postfertilization) it was elevated three times. At the protein level a transient increase in HIF-1α was observed in hypoxic larvae, whereas in the exercise group the amount of HIF-1α protein even decreased below the level of control animals. The analyzed transcriptome was more affected in hypoxic zebrafish larvae, and hardly any genes were similarly altered by both treatments. These results clearly showed that HIF proteins played different roles in trained and hypoxic zebrafish larvae and that the exercise-induced transition to a more aerobic phenotype was not achieved by persistent activation of the hypoxic signaling pathway.
authors.affiliation: Institut für Zoologie and Center for Molecular Biosciences, Universität Innsbruck, Innsbruck, Austria.
authors.forename: Renate
authors.initials: R
authors.lastname: Kopp
authors.forename: Louise
authors.initials: L
authors.lastname: Köblitz
authors.forename: Margit
authors.initials: M
authors.lastname: Egg
authors.forename: Bernd
authors.initials: B
authors.lastname: Pelster
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D015870:Gene Expression; D020869:Gene Expression Profiling; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007814:Larva / Q000235:genetics / Q000378:metabolism; D010805:Physical Conditioning, Animal; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020033:Protein Isoforms; D029961:Zebrafish Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1