Alteration of ZnT5-Mediated Zinc Import into the Early Secretory Pathway Affects the Secretion of Growth Hormone from Rat Pituitary Cells
Background: Aggregation of growth hormone (GH) required for its proper storage in granules is facilitated by zinc (Zn 2+ ) transported by specific zinc transporters in and out of the regulated secretory pathway. Slc30a5 (ZnT5) was reported to have the highest gene expression among all zinc transport...
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| Veröffentlicht in: | Hormone research in paediatrics 2014-01, Vol.82 (4), p.245-251 |
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| creator | Petkovic, Vibor Miletta, Maria Consolata Eblé, Andrée Flück, Christa E. Mullis, Primus-E. |
| description | Background: Aggregation of growth hormone (GH) required for its proper storage in granules is facilitated by zinc (Zn 2+ ) transported by specific zinc transporters in and out of the regulated secretory pathway. Slc30a5 (ZnT5) was reported to have the highest gene expression among all zinc transporters in primary mouse pituitary cells while ZnT5-null mice presented with abnormal bone development and impaired growth compared to wild-type counterparts. Methods: In vitro studies performed in GH3 cells, a rat pituitary cell line that endogenously produces rat GH (rGH), included analysis of: cytoplasmic Zn 2+ pool changes after altering rSlc30a5 expression (luciferase assay), rZnT5 association with different compartments of the regulated secretory pathway (confocal microscopy), and the rGH secretion after rSlc30a5 knock-down (Western blot). Results: Confocal microscopy demonstrated high co-localization of rZnT5 with ER and Golgi (early secretory pathway) while siRNA-mediated knock-down of rSlc30a5 gene expression led to a significant reduction in rGH secretion. Furthermore, altered expression of rSlc30a5 (knock-down/overexpression) evoked changes in the cytoplasmic Zn 2+ pool indicating its important role in mediating Zn 2+ influx into intracellular compartments of the regulated secretory pathway. Conclusion: Taken together, these results suggest that ZnT5 might play an important role in regulated GH secretion that is much greater than previously anticipated. |
| doi_str_mv | 10.1159/000365924 |
| format | Article |
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Slc30a5 (ZnT5) was reported to have the highest gene expression among all zinc transporters in primary mouse pituitary cells while ZnT5-null mice presented with abnormal bone development and impaired growth compared to wild-type counterparts. Methods: In vitro studies performed in GH3 cells, a rat pituitary cell line that endogenously produces rat GH (rGH), included analysis of: cytoplasmic Zn 2+ pool changes after altering rSlc30a5 expression (luciferase assay), rZnT5 association with different compartments of the regulated secretory pathway (confocal microscopy), and the rGH secretion after rSlc30a5 knock-down (Western blot). Results: Confocal microscopy demonstrated high co-localization of rZnT5 with ER and Golgi (early secretory pathway) while siRNA-mediated knock-down of rSlc30a5 gene expression led to a significant reduction in rGH secretion. Furthermore, altered expression of rSlc30a5 (knock-down/overexpression) evoked changes in the cytoplasmic Zn 2+ pool indicating its important role in mediating Zn 2+ influx into intracellular compartments of the regulated secretory pathway. Conclusion: Taken together, these results suggest that ZnT5 might play an important role in regulated GH secretion that is much greater than previously anticipated.</description><identifier>ISSN: 1663-2818</identifier><identifier>EISSN: 1663-2826</identifier><identifier>DOI: 10.1159/000365924</identifier><identifier>PMID: 25196974</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Animals ; Cation Transport Proteins - genetics ; Cell Line ; Cytoplasm - metabolism ; DNA, Complementary - genetics ; Gene Knockdown Techniques ; Growth Hormone - metabolism ; Original Paper ; Pituitary Gland - cytology ; Pituitary Gland - metabolism ; Rats ; RNA, Small Interfering - genetics ; Secretory Pathway - genetics ; Zinc - metabolism</subject><ispartof>Hormone research in paediatrics, 2014-01, Vol.82 (4), p.245-251</ispartof><rights>2014 S. Karger AG, Basel</rights><rights>2014 S. Karger AG, Basel.</rights><rights>Copyright (c) 2014 S. Karger AG, Basel</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c369t-cbd71bc8acd66326d48522ca9264fd5d784c39dd86490c3cd121721b8b8c9f803</citedby><cites>FETCH-LOGICAL-c369t-cbd71bc8acd66326d48522ca9264fd5d784c39dd86490c3cd121721b8b8c9f803</cites><orcidid>0000-0002-4568-5504</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,2422,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25196974$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Petkovic, Vibor</creatorcontrib><creatorcontrib>Miletta, Maria Consolata</creatorcontrib><creatorcontrib>Eblé, Andrée</creatorcontrib><creatorcontrib>Flück, Christa E.</creatorcontrib><creatorcontrib>Mullis, Primus-E.</creatorcontrib><title>Alteration of ZnT5-Mediated Zinc Import into the Early Secretory Pathway Affects the Secretion of Growth Hormone from Rat Pituitary Cells</title><title>Hormone research in paediatrics</title><addtitle>Horm Res Paediatr</addtitle><description>Background: Aggregation of growth hormone (GH) required for its proper storage in granules is facilitated by zinc (Zn 2+ ) transported by specific zinc transporters in and out of the regulated secretory pathway. Slc30a5 (ZnT5) was reported to have the highest gene expression among all zinc transporters in primary mouse pituitary cells while ZnT5-null mice presented with abnormal bone development and impaired growth compared to wild-type counterparts. Methods: In vitro studies performed in GH3 cells, a rat pituitary cell line that endogenously produces rat GH (rGH), included analysis of: cytoplasmic Zn 2+ pool changes after altering rSlc30a5 expression (luciferase assay), rZnT5 association with different compartments of the regulated secretory pathway (confocal microscopy), and the rGH secretion after rSlc30a5 knock-down (Western blot). Results: Confocal microscopy demonstrated high co-localization of rZnT5 with ER and Golgi (early secretory pathway) while siRNA-mediated knock-down of rSlc30a5 gene expression led to a significant reduction in rGH secretion. Furthermore, altered expression of rSlc30a5 (knock-down/overexpression) evoked changes in the cytoplasmic Zn 2+ pool indicating its important role in mediating Zn 2+ influx into intracellular compartments of the regulated secretory pathway. Conclusion: Taken together, these results suggest that ZnT5 might play an important role in regulated GH secretion that is much greater than previously anticipated.</description><subject>Animals</subject><subject>Cation Transport Proteins - genetics</subject><subject>Cell Line</subject><subject>Cytoplasm - metabolism</subject><subject>DNA, Complementary - genetics</subject><subject>Gene Knockdown Techniques</subject><subject>Growth Hormone - metabolism</subject><subject>Original Paper</subject><subject>Pituitary Gland - cytology</subject><subject>Pituitary Gland - metabolism</subject><subject>Rats</subject><subject>RNA, Small Interfering - genetics</subject><subject>Secretory Pathway - genetics</subject><subject>Zinc - metabolism</subject><issn>1663-2818</issn><issn>1663-2826</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpd0ctKxDAUBuAgioq6cC8ScKOLak7apslyGLwMjCheNm5KmqROtW3GJEXmEXxrozPOwlUC-fJzDj9Ch0DOAXJxQQhJWS5otoF2gbE0oZyyzfUd-A468P6N_DheCCi20Q7NQTBRZLvoa9QG42RobI9tjV_6pzy5NbqRwWj80vQKT7q5dQE3fbA4zAy-lK5d4EejnAnWLfC9DLNPucCjujYq-F-zfF1lXjv7GWb4xrrO9gbXznb4QQZ834ShCTJGjE3b-n20VcvWm4PVuYeery6fxjfJ9O56Mh5NE5UyERJV6QIqxaXScUHKdMZzSpUUlGW1znXBM5UKrTnLBFGp0kChoFDxiitRc5LuodNl7tzZj8H4UHaNV3EC2Rs7-BIYkIJBJlikJ__omx1cH6eLihYAacZEVGdLpZz13pm6nLumi3uVQMqfisp1RdEerxKHqjN6Lf8KieBoCd6lezVuDVb_vwG2PZQh</recordid><startdate>20140101</startdate><enddate>20140101</enddate><creator>Petkovic, Vibor</creator><creator>Miletta, Maria Consolata</creator><creator>Eblé, Andrée</creator><creator>Flück, Christa E.</creator><creator>Mullis, Primus-E.</creator><general>S. Karger AG</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4568-5504</orcidid></search><sort><creationdate>20140101</creationdate><title>Alteration of ZnT5-Mediated Zinc Import into the Early Secretory Pathway Affects the Secretion of Growth Hormone from Rat Pituitary Cells</title><author>Petkovic, Vibor ; Miletta, Maria Consolata ; Eblé, Andrée ; Flück, Christa E. ; Mullis, Primus-E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c369t-cbd71bc8acd66326d48522ca9264fd5d784c39dd86490c3cd121721b8b8c9f803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Cation Transport Proteins - genetics</topic><topic>Cell Line</topic><topic>Cytoplasm - metabolism</topic><topic>DNA, Complementary - genetics</topic><topic>Gene Knockdown Techniques</topic><topic>Growth Hormone - metabolism</topic><topic>Original Paper</topic><topic>Pituitary Gland - cytology</topic><topic>Pituitary Gland - metabolism</topic><topic>Rats</topic><topic>RNA, Small Interfering - genetics</topic><topic>Secretory Pathway - genetics</topic><topic>Zinc - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Petkovic, Vibor</creatorcontrib><creatorcontrib>Miletta, Maria Consolata</creatorcontrib><creatorcontrib>Eblé, Andrée</creatorcontrib><creatorcontrib>Flück, Christa E.</creatorcontrib><creatorcontrib>Mullis, Primus-E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Source (ProQuest)</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Databases</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>Consumer Health Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Hormone research in paediatrics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Petkovic, Vibor</au><au>Miletta, Maria Consolata</au><au>Eblé, Andrée</au><au>Flück, Christa E.</au><au>Mullis, Primus-E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alteration of ZnT5-Mediated Zinc Import into the Early Secretory Pathway Affects the Secretion of Growth Hormone from Rat Pituitary Cells</atitle><jtitle>Hormone research in paediatrics</jtitle><addtitle>Horm Res Paediatr</addtitle><date>2014-01-01</date><risdate>2014</risdate><volume>82</volume><issue>4</issue><spage>245</spage><epage>251</epage><pages>245-251</pages><issn>1663-2818</issn><eissn>1663-2826</eissn><abstract>Background: Aggregation of growth hormone (GH) required for its proper storage in granules is facilitated by zinc (Zn 2+ ) transported by specific zinc transporters in and out of the regulated secretory pathway. Slc30a5 (ZnT5) was reported to have the highest gene expression among all zinc transporters in primary mouse pituitary cells while ZnT5-null mice presented with abnormal bone development and impaired growth compared to wild-type counterparts. Methods: In vitro studies performed in GH3 cells, a rat pituitary cell line that endogenously produces rat GH (rGH), included analysis of: cytoplasmic Zn 2+ pool changes after altering rSlc30a5 expression (luciferase assay), rZnT5 association with different compartments of the regulated secretory pathway (confocal microscopy), and the rGH secretion after rSlc30a5 knock-down (Western blot). Results: Confocal microscopy demonstrated high co-localization of rZnT5 with ER and Golgi (early secretory pathway) while siRNA-mediated knock-down of rSlc30a5 gene expression led to a significant reduction in rGH secretion. Furthermore, altered expression of rSlc30a5 (knock-down/overexpression) evoked changes in the cytoplasmic Zn 2+ pool indicating its important role in mediating Zn 2+ influx into intracellular compartments of the regulated secretory pathway. Conclusion: Taken together, these results suggest that ZnT5 might play an important role in regulated GH secretion that is much greater than previously anticipated.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>25196974</pmid><doi>10.1159/000365924</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-4568-5504</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Cation Transport Proteins - genetics Cell Line Cytoplasm - metabolism DNA, Complementary - genetics Gene Knockdown Techniques Growth Hormone - metabolism Original Paper Pituitary Gland - cytology Pituitary Gland - metabolism Rats RNA, Small Interfering - genetics Secretory Pathway - genetics Zinc - metabolism |
| title | Alteration of ZnT5-Mediated Zinc Import into the Early Secretory Pathway Affects the Secretion of Growth Hormone from Rat Pituitary Cells |
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