PUBLICATION

CRF and urocortin 3 protect the heart from hypoxia/reoxygenation-induced apoptosis in zebrafish

Authors
Williams, T.A., Bergstrome, J.C., Scott, J., Bernier, N.J.
ID
ZDB-PUB-170526-12
Date
2017
Source
American journal of physiology. Regulatory, integrative and comparative physiology   313(2): R91-R100 (Journal)
Registered Authors
Keywords
CRH, UCN3, cytoprotection, heart, hypoxia
MeSH Terms
  • Animals
  • Apoptosis*
  • Corticotropin-Releasing Hormone/metabolism*
  • Heart/physiopathology*
  • Male
  • Myocardial Reperfusion Injury/physiopathology*
  • Tissue Distribution
  • Urocortins/metabolism*
  • Zebrafish/physiology*
PubMed
28539353 Full text @ Am. J. Physiol. Regul. Integr. Comp. Physiol.
Abstract
Fish routinely experience environmental hypoxia and have evolved various strategies to tolerate this challenge. Given the key role of the CRF system in coordinating the response to stressors and its cardioprotective actions against ischemia in mammals, we sought to characterize the cardiac CRF system in zebrafish and its role in hypoxia tolerance. We established that all genes of the CRF system, the ligands CRFa, CRFb, urotensin 1 (UTS1), and urocortin 3 (UCN3); the two receptor subtypes (CRFR1 and CRFR2); and the binding protein (CRFBP) are expressed in the heart of zebrafish: crfr1 > crfr2 = crfbp > crfa > ucn3 > crfb > uts1 In vivo, exposure to 5% O2 saturation for 15 min and 90 min of recovery resulted in four- to five-fold increases in whole heart crfb and ucn3 mRNA levels but did not affect the gene expression of other CRF system components. In vitro, as assessed by monitoring caspase 3 activity and the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells, pretreatment of excised whole hearts with CRF or UCN3 for 30 min prevented the increase in apoptosis associated with exposure to 1% O2 saturation for 30 min with a 24-h recovery. Lastly, the addition of the nonselective CRF receptor antagonist αh-CRF(9-41) prevented the cytoprotective effects of CRF. We show that the CRF system is expressed in fish heart, is upregulated by hypoxia, and is cytoprotective. These findings identify a novel role for the CRF system in fish and a new strategy to tolerate hypoxia.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping