ZFIN ID: ZDB-PUB-110316-22
HIF signaling and overall gene expression changes during hypoxia and prolonged exercise differ considerably
Kopp, R., Köblitz, L., Egg, M., and Pelster, B.
Date: 2011
Source: Physiological Genomics   43(9): 506-516 (Journal)
Registered Authors: Kopp, Renate, Pelster, Bernd
Keywords: Ontogeny, exercise, hypoxia, hypoxic signaling, zebrafish
MeSH Terms:
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors/genetics
  • Basic Helix-Loop-Helix Transcription Factors/metabolism*
  • Cell Hypoxia/genetics
  • Cell Hypoxia/physiology
  • Gene Expression*
  • Gene Expression Profiling
  • Hypoxia-Inducible Factor 1, alpha Subunit/genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
  • Larva/genetics
  • Larva/metabolism
  • Physical Conditioning, Animal
  • Protein Isoforms/genetics
  • Protein Isoforms/metabolism
  • Signal Transduction*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 21343420 Full text @ Physiol. Genomics
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 which were raised under normoxic, hypoxic or training conditions were compared, using microarray analysis, quantitative real time PCR and protein data. Although HIF expression is post-translationally 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 to 15 days post fertilization) 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 gene was 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.