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

The present study investigated the potential role of hypoxia-inducible factor (HIF) on calcium homeostasis in developing zebrafish (Danio rerio). It was demonstrated that zebrafish raised in hypoxic water (30 mmHg; control=155 mmHg) until 4 days post fertilisation exhibited a substantial reduction i...

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Veröffentlicht in:Journal of experimental biology 2016-01
Hauptverfasser: Kwong, Raymond W. M., Kumai, Yusuke, Tzaneva, Velislava, Azzi, Estelle, Hochhold, Nina, Robertson, Cayleih, Pelster, Bernd, Perry, Steve F.
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Sprache:eng
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Zusammenfassung:The present study investigated the potential role of hypoxia-inducible factor (HIF) on calcium homeostasis in developing zebrafish (Danio rerio). It was demonstrated that zebrafish raised in hypoxic water (30 mmHg; control=155 mmHg) until 4 days post fertilisation 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 after transferring 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) nor 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, likely owing to HIF-1αb-mediated suppression of ecac expression.
ISSN:0022-0949
1477-9145
DOI:10.1242/jeb.148700