Inhibition of calcium uptake during hypoxia in developing zebrafish is mediated by hypoxia-inducible factor
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 P ) until 4 days post-fertilization exhibited a substantial reducti...
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creator | Kwong, Raymond W M Kumai, Yusuke Tzaneva, Velislava Azzi, Estelle Hochhold, Nina Robertson, Cayleih Pelster, Bernd Perry, Steve F |
description | 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 P
) until 4 days post-fertilization exhibited a substantial reduction in whole-body Ca
levels and Ca
uptake. Ca
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 Ca
channel (ecac), but not plasma membrane Ca
-ATPase (pmca2) or Na
/Ca
-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 Ca
influx. To further evaluate the potential mechanisms for the effects of hypoxia on Ca
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 Ca
balance during hypoxia, the results demonstrated that the reduction of Ca
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 Ca
uptake in developing zebrafish, probably owing to HIF-1αb-mediated suppression of ecac expression. |
doi_str_mv | 10.1242/jeb.148700 |
format | Article |
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) until 4 days post-fertilization exhibited a substantial reduction in whole-body Ca
levels and Ca
uptake. Ca
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 Ca
channel (ecac), but not plasma membrane Ca
-ATPase (pmca2) or Na
/Ca
-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 Ca
influx. To further evaluate the potential mechanisms for the effects of hypoxia on Ca
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 Ca
balance during hypoxia, the results demonstrated that the reduction of Ca
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 Ca
uptake in developing zebrafish, probably owing to HIF-1αb-mediated suppression of ecac expression.</description><identifier>ISSN: 0022-0949</identifier><identifier>EISSN: 1477-9145</identifier><identifier>DOI: 10.1242/jeb.148700</identifier><identifier>PMID: 27802147</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Biological Transport - drug effects ; Biological Transport - genetics ; Calcium - metabolism ; Cell Count ; Danio rerio ; 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</subject><ispartof>Journal of experimental biology, 2016-12, Vol.219 (Pt 24), p.3988-3995</ispartof><rights>2016. Published by The Company of Biologists Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-0784-9651</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27802147$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kwong, Raymond W M</creatorcontrib><creatorcontrib>Kumai, Yusuke</creatorcontrib><creatorcontrib>Tzaneva, Velislava</creatorcontrib><creatorcontrib>Azzi, Estelle</creatorcontrib><creatorcontrib>Hochhold, Nina</creatorcontrib><creatorcontrib>Robertson, Cayleih</creatorcontrib><creatorcontrib>Pelster, Bernd</creatorcontrib><creatorcontrib>Perry, Steve F</creatorcontrib><title>Inhibition of calcium uptake during hypoxia in developing zebrafish is mediated by hypoxia-inducible factor</title><title>Journal of experimental biology</title><addtitle>J Exp Biol</addtitle><description>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 P
) until 4 days post-fertilization exhibited a substantial reduction in whole-body Ca
levels and Ca
uptake. Ca
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 Ca
channel (ecac), but not plasma membrane Ca
-ATPase (pmca2) or Na
/Ca
-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 Ca
influx. To further evaluate the potential mechanisms for the effects of hypoxia on Ca
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 Ca
balance during hypoxia, the results demonstrated that the reduction of Ca
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 Ca
uptake in developing zebrafish, probably owing to HIF-1αb-mediated suppression of ecac expression.</description><subject>Animals</subject><subject>Biological Transport - drug effects</subject><subject>Biological Transport - genetics</subject><subject>Calcium - metabolism</subject><subject>Cell Count</subject><subject>Danio rerio</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Gene Knockdown Techniques</subject><subject>Hypoxia - metabolism</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</subject><subject>Ions</subject><subject>Morpholinos - pharmacology</subject><subject>Protein Stability - drug effects</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>TRPV Cation Channels - genetics</subject><subject>TRPV Cation Channels - metabolism</subject><subject>Zebrafish - genetics</subject><subject>Zebrafish - metabolism</subject><subject>Zebrafish Proteins - genetics</subject><subject>Zebrafish Proteins - metabolism</subject><issn>0022-0949</issn><issn>1477-9145</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkDtPwzAUhS0EoqWw8AOQR5YUP27seEQVj0qVWGCO7NimbvMiThDh1xNEu3OXIx19OtJ3EbqmZEkZsLudM0sKmSTkBM0pSJkoCukpmhPCWEIUqBm6iHFHphMpnKMZkxlhEzlH-3W9DSb0oalx43GhyyIMFR7aXu8dtkMX6ne8HdvmK2gcamzdpyub9rf9dqbTPsQtDhFXzgbdO4vNeMSTUNuhCKZ02Ouib7pLdOZ1Gd3VIRfo7fHhdfWcbF6e1qv7TdIygD7RDDLQwnIqiZV8cgEnRJYaSDVoEJqDF9ZIVlhPHTCVWpJNNsITyaz1fIFu_3bbrvkYXOzzKsTClaWuXTPEnGYi44wIQf-BclBKMRATenNABzPZ5m0XKt2N-fGX_AcVOXXH</recordid><startdate>20161215</startdate><enddate>20161215</enddate><creator>Kwong, Raymond W M</creator><creator>Kumai, Yusuke</creator><creator>Tzaneva, Velislava</creator><creator>Azzi, Estelle</creator><creator>Hochhold, Nina</creator><creator>Robertson, Cayleih</creator><creator>Pelster, Bernd</creator><creator>Perry, Steve F</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>7QP</scope><orcidid>https://orcid.org/0000-0002-0784-9651</orcidid></search><sort><creationdate>20161215</creationdate><title>Inhibition of calcium uptake during hypoxia in developing zebrafish is mediated by hypoxia-inducible factor</title><author>Kwong, Raymond W M ; Kumai, Yusuke ; Tzaneva, Velislava ; Azzi, Estelle ; Hochhold, Nina ; Robertson, Cayleih ; Pelster, Bernd ; Perry, Steve F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p244t-a2484a6d3170d739144e6685b45a4a46a34f6db72cdf1e4295d082146f072ddf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Biological Transport - drug effects</topic><topic>Biological Transport - genetics</topic><topic>Calcium - metabolism</topic><topic>Cell Count</topic><topic>Danio rerio</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Gene Knockdown Techniques</topic><topic>Hypoxia - metabolism</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</topic><topic>Ions</topic><topic>Morpholinos - pharmacology</topic><topic>Protein Stability - drug effects</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>TRPV Cation Channels - genetics</topic><topic>TRPV Cation Channels - metabolism</topic><topic>Zebrafish - genetics</topic><topic>Zebrafish - metabolism</topic><topic>Zebrafish Proteins - genetics</topic><topic>Zebrafish Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kwong, Raymond W M</creatorcontrib><creatorcontrib>Kumai, Yusuke</creatorcontrib><creatorcontrib>Tzaneva, Velislava</creatorcontrib><creatorcontrib>Azzi, Estelle</creatorcontrib><creatorcontrib>Hochhold, Nina</creatorcontrib><creatorcontrib>Robertson, Cayleih</creatorcontrib><creatorcontrib>Pelster, Bernd</creatorcontrib><creatorcontrib>Perry, Steve F</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>Calcium & Calcified Tissue Abstracts</collection><jtitle>Journal of experimental biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kwong, Raymond W M</au><au>Kumai, Yusuke</au><au>Tzaneva, Velislava</au><au>Azzi, Estelle</au><au>Hochhold, Nina</au><au>Robertson, Cayleih</au><au>Pelster, Bernd</au><au>Perry, Steve F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of calcium uptake during hypoxia in developing zebrafish is mediated by hypoxia-inducible factor</atitle><jtitle>Journal of experimental biology</jtitle><addtitle>J Exp Biol</addtitle><date>2016-12-15</date><risdate>2016</risdate><volume>219</volume><issue>Pt 24</issue><spage>3988</spage><epage>3995</epage><pages>3988-3995</pages><issn>0022-0949</issn><eissn>1477-9145</eissn><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 P
) until 4 days post-fertilization exhibited a substantial reduction in whole-body Ca
levels and Ca
uptake. Ca
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 Ca
channel (ecac), but not plasma membrane Ca
-ATPase (pmca2) or Na
/Ca
-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 Ca
influx. To further evaluate the potential mechanisms for the effects of hypoxia on Ca
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 Ca
balance during hypoxia, the results demonstrated that the reduction of Ca
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 Ca
uptake in developing zebrafish, probably owing to HIF-1αb-mediated suppression of ecac expression.</abstract><cop>England</cop><pmid>27802147</pmid><doi>10.1242/jeb.148700</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-0784-9651</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animals Biological Transport - drug effects Biological Transport - genetics Calcium - metabolism Cell Count Danio rerio 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 |
title | Inhibition of calcium uptake during hypoxia in developing zebrafish is mediated by hypoxia-inducible factor |
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