Novel Genes Critical for Hypoxic Preconditioning in Zebrafish Are Regulators of Insulin and Glucose Metabolism

G3 (Bethesda). 2015 Apr 3;5(6):1107-16. doi: 10.1534/g3.115.018010.

Abstract

Severe hypoxia is a common cause of major brain, heart, and kidney injury in adults, children, and newborns. However, mild hypoxia can be protective against later, more severe hypoxia exposure via "hypoxic preconditioning," a phenomenon that is not yet fully understood. Accordingly, we have established and optimized an embryonic zebrafish model to study hypoxic preconditioning. Using a functional genomic approach, we used this zebrafish model to identify and validate five novel hypoxia-protective genes, including irs2, crtc3, and camk2g2, which have been previously implicated in metabolic regulation. These results extend our understanding of the mechanisms of hypoxic preconditioning and affirm the discovery potential of this novel vertebrate hypoxic stress model.

Keywords: hormesis; hypoxia-ischemia; metabolic state; preconditioning; stress tolerance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Embryo, Nonmammalian / metabolism
  • Gene Expression Profiling
  • Gene Knockdown Techniques
  • Genome
  • Glucose / metabolism*
  • Hypoxia / genetics*
  • Insulin / metabolism*
  • Phenotype
  • Real-Time Polymerase Chain Reaction
  • Reproducibility of Results
  • Stress, Physiological / genetics
  • Transcription, Genetic
  • Zebrafish / embryology
  • Zebrafish / genetics*
  • Zebrafish / metabolism*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • Insulin
  • Zebrafish Proteins
  • Glucose