PUBLICATION

Inhibition of calcium uptake during hypoxia in developing zebrafish, is mediated by hypoxia-inducible factor

Authors
Kwong, R.W., Kumai, Y., Tzaneva, V., Azzi, E., Hochhold, N., Robertson, C., Pelster, B., Perry, S.F.
ID
ZDB-PUB-161102-3
Date
2016
Source
The Journal of experimental biology   219(Pt 24): 3988-3995 (Journal)
Registered Authors
Pelster, Bernd, Perry, Steve F.
Keywords
Calcium, ECaC, Ion regulation, HIF, fish, Ionocyte
MeSH Terms
  • Animals
  • Biological Transport/drug effects
  • Biological Transport/genetics
  • Calcium/metabolism*
  • Cell Count
  • Gene Expression Regulation/drug effects
  • Gene Knockdown Techniques
  • Hypoxia/metabolism*
  • Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
  • Ions
  • Morpholinos/pharmacology
  • Protein Stability/drug effects
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • TRPV Cation Channels/genetics
  • TRPV Cation Channels/metabolism
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
27802147 Full text @ J. Exp. Biol.
Abstract
The present study investigated the potential role of hypoxia-inducible factor (HIF) in calcium homeostasis in developing zebrafish (Danio rerio). It was demonstrated that zebrafish raised in hypoxic water (30 mmHg; control, 155 mmHg PO2 ) until 4 days post-fertilization exhibited a substantial reduction in whole-body Ca2+ levels and Ca2+ uptake. Ca2+ uptake in hypoxia-treated fish did not return to pre-hypoxia (control) levels within 2 h of transfer back to normoxic water. Results from real-time PCR showed that hypoxia decreased the whole-body mRNA expression levels of the epithelial Ca2+ channel (ecac), but not plasma membrane Ca2+-ATPase (pmca2) or Na+/Ca2+-exchanger (ncx1b). Whole-mount in situ hybridization revealed that the number of ecac-expressing ionocytes was reduced in fish raised in hypoxic water. These findings suggested that hypoxic treatment suppressed the expression of ecac, thereby reducing Ca2+ influx. To further evaluate the potential mechanisms for the effects of hypoxia on Ca2+ regulation, a functional gene knockdown approach was employed to prevent the expression of HIF-1αb during hypoxic treatment. Consistent with a role for HIF-1αb in regulating Ca2+ balance during hypoxia, the results demonstrated that the reduction of Ca2+ uptake associated with hypoxic exposure was not observed in fish experiencing HIF-1αb knockdown. Additionally, the effects of hypoxia on reducing the number of ecac-expressing ionocytes was less pronounced in HIF-1αb-deficient fish. Overall, the current study revealed that hypoxic exposure inhibited Ca2+ uptake in developing zebrafish, probably owing to HIF-1αb-mediated suppression of ecac expression.
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
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Mapping