SLC41A1 knockdown inhibits angiotensin II-induced cardiac fibrosis by preventing Mg(2+) efflux and Ca(2+) signaling in cardiac fibroblasts
Na(+)/Mg(2+) exchanger plays an important role in cardiovascular system, but the molecular mechanisms still largely remain unknown. The Solute Carrier family 41A1 (SLC41A1), a novel Mg(2+) transporter, recently was found to function as Na(+)/Mg(2+) exchanger, which mainly regulates the intracellular...
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Veröffentlicht in: | Archives of biochemistry and biophysics 2014-12, Vol.564, p.74 |
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description | Na(+)/Mg(2+) exchanger plays an important role in cardiovascular system, but the molecular mechanisms still largely remain unknown. The Solute Carrier family 41A1 (SLC41A1), a novel Mg(2+) transporter, recently was found to function as Na(+)/Mg(2+) exchanger, which mainly regulates the intracellular Mg(2+) ([Mg(2+)]i) homeostasis. Our present studies were designed to investigate whether SLC41A1 impacts on the fibrogenesis of cardiac fibroblasts under Ang II stimulation. Our results showed that quinidine, a prototypical inhibitor of Na(+)/Mg(2+) exchanger, inhibited Ang II-induced cardiac fibrosis via attenuating the overexpression of vital biomarkers of fibrosis, including connective tissue growth factor (CTGF), fibronectin (FN) and α-smooth muscle actin (α-SMA). In addition, quinidine also decreased the Ang II-mediated elevation of concentration of intracellular Ca(2+) ([Ca(2+)]i) and extrusion of intracellular Mg(2+). Meanwhile, silencing SLC41A1 by RNA interference also impaired the elevation of [Ca(2+)]i, [Mg(2+)]i efflux and the upregulation of CTGF, FN and α-SMA provoked by Ang II. Furthermore, we found that Ang II-mediated activation of NFATc4 translocation decreased in SLC41A1-siRNA cells. These results support the notion that rapid extrusion of intracellular Mg(2+) is mediated by SLC41A1 and provide the evidence that the intracellular free Ca(2+) concentration is influenced by extrusion of intracellular Mg(2+) which facilitates fibrosis reaction in cardiac fibroblasts. |
doi_str_mv | 10.1016/j.abb.2014.09.013 |
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The Solute Carrier family 41A1 (SLC41A1), a novel Mg(2+) transporter, recently was found to function as Na(+)/Mg(2+) exchanger, which mainly regulates the intracellular Mg(2+) ([Mg(2+)]i) homeostasis. Our present studies were designed to investigate whether SLC41A1 impacts on the fibrogenesis of cardiac fibroblasts under Ang II stimulation. Our results showed that quinidine, a prototypical inhibitor of Na(+)/Mg(2+) exchanger, inhibited Ang II-induced cardiac fibrosis via attenuating the overexpression of vital biomarkers of fibrosis, including connective tissue growth factor (CTGF), fibronectin (FN) and α-smooth muscle actin (α-SMA). In addition, quinidine also decreased the Ang II-mediated elevation of concentration of intracellular Ca(2+) ([Ca(2+)]i) and extrusion of intracellular Mg(2+). Meanwhile, silencing SLC41A1 by RNA interference also impaired the elevation of [Ca(2+)]i, [Mg(2+)]i efflux and the upregulation of CTGF, FN and α-SMA provoked by Ang II. Furthermore, we found that Ang II-mediated activation of NFATc4 translocation decreased in SLC41A1-siRNA cells. These results support the notion that rapid extrusion of intracellular Mg(2+) is mediated by SLC41A1 and provide the evidence that the intracellular free Ca(2+) concentration is influenced by extrusion of intracellular Mg(2+) which facilitates fibrosis reaction in cardiac fibroblasts.</description><identifier>EISSN: 1096-0384</identifier><identifier>DOI: 10.1016/j.abb.2014.09.013</identifier><identifier>PMID: 25263961</identifier><language>eng</language><publisher>United States</publisher><subject>Angiotensin II - adverse effects ; Angiotensin II - pharmacology ; Animals ; Calcium - metabolism ; Calcium Signaling ; Cation Transport Proteins - genetics ; Cation Transport Proteins - metabolism ; Endomyocardial Fibrosis - chemically induced ; Endomyocardial Fibrosis - genetics ; Endomyocardial Fibrosis - metabolism ; Endomyocardial Fibrosis - pathology ; Fibroblasts - metabolism ; Fibroblasts - pathology ; Gene Knockdown Techniques ; Ion Transport - genetics ; Magnesium - metabolism ; Muscle Proteins - genetics ; Muscle Proteins - metabolism ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; NFATC Transcription Factors - genetics ; NFATC Transcription Factors - metabolism ; Rats ; Rats, Sprague-Dawley ; Vasoconstrictor Agents - adverse effects ; Vasoconstrictor Agents - pharmacology</subject><ispartof>Archives of biochemistry and biophysics, 2014-12, Vol.564, p.74</ispartof><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25263961$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yu, Na</creatorcontrib><creatorcontrib>Jiang, Jianmin</creatorcontrib><creatorcontrib>Yu, Yang</creatorcontrib><creatorcontrib>Li, Hong</creatorcontrib><creatorcontrib>Huang, Xiaoyang</creatorcontrib><creatorcontrib>Ma, Yunzi</creatorcontrib><creatorcontrib>Zhang, Luankun</creatorcontrib><creatorcontrib>Zou, Jian</creatorcontrib><creatorcontrib>Zhang, Boyu</creatorcontrib><creatorcontrib>Chen, Shaorui</creatorcontrib><creatorcontrib>Liu, Peiqing</creatorcontrib><title>SLC41A1 knockdown inhibits angiotensin II-induced cardiac fibrosis by preventing Mg(2+) efflux and Ca(2+) signaling in cardiac fibroblasts</title><title>Archives of biochemistry and biophysics</title><addtitle>Arch Biochem Biophys</addtitle><description>Na(+)/Mg(2+) exchanger plays an important role in cardiovascular system, but the molecular mechanisms still largely remain unknown. The Solute Carrier family 41A1 (SLC41A1), a novel Mg(2+) transporter, recently was found to function as Na(+)/Mg(2+) exchanger, which mainly regulates the intracellular Mg(2+) ([Mg(2+)]i) homeostasis. Our present studies were designed to investigate whether SLC41A1 impacts on the fibrogenesis of cardiac fibroblasts under Ang II stimulation. Our results showed that quinidine, a prototypical inhibitor of Na(+)/Mg(2+) exchanger, inhibited Ang II-induced cardiac fibrosis via attenuating the overexpression of vital biomarkers of fibrosis, including connective tissue growth factor (CTGF), fibronectin (FN) and α-smooth muscle actin (α-SMA). In addition, quinidine also decreased the Ang II-mediated elevation of concentration of intracellular Ca(2+) ([Ca(2+)]i) and extrusion of intracellular Mg(2+). Meanwhile, silencing SLC41A1 by RNA interference also impaired the elevation of [Ca(2+)]i, [Mg(2+)]i efflux and the upregulation of CTGF, FN and α-SMA provoked by Ang II. Furthermore, we found that Ang II-mediated activation of NFATc4 translocation decreased in SLC41A1-siRNA cells. These results support the notion that rapid extrusion of intracellular Mg(2+) is mediated by SLC41A1 and provide the evidence that the intracellular free Ca(2+) concentration is influenced by extrusion of intracellular Mg(2+) which facilitates fibrosis reaction in cardiac fibroblasts.</description><subject>Angiotensin II - adverse effects</subject><subject>Angiotensin II - pharmacology</subject><subject>Animals</subject><subject>Calcium - metabolism</subject><subject>Calcium Signaling</subject><subject>Cation Transport Proteins - genetics</subject><subject>Cation Transport Proteins - metabolism</subject><subject>Endomyocardial Fibrosis - chemically induced</subject><subject>Endomyocardial Fibrosis - genetics</subject><subject>Endomyocardial Fibrosis - metabolism</subject><subject>Endomyocardial Fibrosis - pathology</subject><subject>Fibroblasts - metabolism</subject><subject>Fibroblasts - pathology</subject><subject>Gene Knockdown Techniques</subject><subject>Ion Transport - genetics</subject><subject>Magnesium - metabolism</subject><subject>Muscle Proteins - genetics</subject><subject>Muscle Proteins - metabolism</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>NFATC Transcription Factors - genetics</subject><subject>NFATC Transcription Factors - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Vasoconstrictor Agents - adverse effects</subject><subject>Vasoconstrictor Agents - pharmacology</subject><issn>1096-0384</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkMtKw0AYhQdBbK0-gBuZpSKJ80_SSbIswUuh4kJdl39ucdp0EjKp2lfwqU29LFwdzuHwwTmEnAGLgYG4XsUoZcwZpDErYgbJARkDK0TEkjwdkeMQVowBpIIfkRGfcpEUAsbk82lRpjADuvaNWuvm3VPnX510faDoK9f0xgfn6XweOa-3ymiqsNMOFbVOdk1wgcodbTvzZnzvfEUfqgt-dUmNtfX2Y2BoWuJ3Elzlsd5XBt4_iKwx9OGEHFqsgzn91Ql5ub15Lu-jxePdvJwtoha46KMMILOFMQqmuc2GSVonkGVqH-YCmBSMazRFOjiOaFAJblHngknM9NQkE3L-w223cmP0su3cBrvd8u-U5AtOIGNv</recordid><startdate>20141215</startdate><enddate>20141215</enddate><creator>Yu, Na</creator><creator>Jiang, Jianmin</creator><creator>Yu, Yang</creator><creator>Li, Hong</creator><creator>Huang, Xiaoyang</creator><creator>Ma, Yunzi</creator><creator>Zhang, Luankun</creator><creator>Zou, Jian</creator><creator>Zhang, Boyu</creator><creator>Chen, Shaorui</creator><creator>Liu, Peiqing</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20141215</creationdate><title>SLC41A1 knockdown inhibits angiotensin II-induced cardiac fibrosis by preventing Mg(2+) efflux and Ca(2+) signaling in cardiac fibroblasts</title><author>Yu, Na ; Jiang, Jianmin ; Yu, Yang ; Li, Hong ; Huang, Xiaoyang ; Ma, Yunzi ; Zhang, Luankun ; Zou, Jian ; Zhang, Boyu ; Chen, Shaorui ; Liu, Peiqing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p126t-7117f9eec158f7011dd3177c7f9e8610b602dae94e862aaeac62fad860ba7d5e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Angiotensin II - adverse effects</topic><topic>Angiotensin II - pharmacology</topic><topic>Animals</topic><topic>Calcium - metabolism</topic><topic>Calcium Signaling</topic><topic>Cation Transport Proteins - genetics</topic><topic>Cation Transport Proteins - metabolism</topic><topic>Endomyocardial Fibrosis - chemically induced</topic><topic>Endomyocardial Fibrosis - genetics</topic><topic>Endomyocardial Fibrosis - metabolism</topic><topic>Endomyocardial Fibrosis - pathology</topic><topic>Fibroblasts - metabolism</topic><topic>Fibroblasts - pathology</topic><topic>Gene Knockdown Techniques</topic><topic>Ion Transport - genetics</topic><topic>Magnesium - metabolism</topic><topic>Muscle Proteins - genetics</topic><topic>Muscle Proteins - metabolism</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>NFATC Transcription Factors - genetics</topic><topic>NFATC Transcription Factors - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Vasoconstrictor Agents - adverse effects</topic><topic>Vasoconstrictor Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yu, Na</creatorcontrib><creatorcontrib>Jiang, Jianmin</creatorcontrib><creatorcontrib>Yu, Yang</creatorcontrib><creatorcontrib>Li, Hong</creatorcontrib><creatorcontrib>Huang, Xiaoyang</creatorcontrib><creatorcontrib>Ma, Yunzi</creatorcontrib><creatorcontrib>Zhang, Luankun</creatorcontrib><creatorcontrib>Zou, Jian</creatorcontrib><creatorcontrib>Zhang, Boyu</creatorcontrib><creatorcontrib>Chen, Shaorui</creatorcontrib><creatorcontrib>Liu, Peiqing</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Archives of biochemistry and biophysics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yu, Na</au><au>Jiang, Jianmin</au><au>Yu, Yang</au><au>Li, Hong</au><au>Huang, Xiaoyang</au><au>Ma, Yunzi</au><au>Zhang, Luankun</au><au>Zou, Jian</au><au>Zhang, Boyu</au><au>Chen, Shaorui</au><au>Liu, Peiqing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SLC41A1 knockdown inhibits angiotensin II-induced cardiac fibrosis by preventing Mg(2+) efflux and Ca(2+) signaling in cardiac fibroblasts</atitle><jtitle>Archives of biochemistry and biophysics</jtitle><addtitle>Arch Biochem Biophys</addtitle><date>2014-12-15</date><risdate>2014</risdate><volume>564</volume><spage>74</spage><pages>74-</pages><eissn>1096-0384</eissn><abstract>Na(+)/Mg(2+) exchanger plays an important role in cardiovascular system, but the molecular mechanisms still largely remain unknown. The Solute Carrier family 41A1 (SLC41A1), a novel Mg(2+) transporter, recently was found to function as Na(+)/Mg(2+) exchanger, which mainly regulates the intracellular Mg(2+) ([Mg(2+)]i) homeostasis. Our present studies were designed to investigate whether SLC41A1 impacts on the fibrogenesis of cardiac fibroblasts under Ang II stimulation. Our results showed that quinidine, a prototypical inhibitor of Na(+)/Mg(2+) exchanger, inhibited Ang II-induced cardiac fibrosis via attenuating the overexpression of vital biomarkers of fibrosis, including connective tissue growth factor (CTGF), fibronectin (FN) and α-smooth muscle actin (α-SMA). In addition, quinidine also decreased the Ang II-mediated elevation of concentration of intracellular Ca(2+) ([Ca(2+)]i) and extrusion of intracellular Mg(2+). Meanwhile, silencing SLC41A1 by RNA interference also impaired the elevation of [Ca(2+)]i, [Mg(2+)]i efflux and the upregulation of CTGF, FN and α-SMA provoked by Ang II. Furthermore, we found that Ang II-mediated activation of NFATc4 translocation decreased in SLC41A1-siRNA cells. These results support the notion that rapid extrusion of intracellular Mg(2+) is mediated by SLC41A1 and provide the evidence that the intracellular free Ca(2+) concentration is influenced by extrusion of intracellular Mg(2+) which facilitates fibrosis reaction in cardiac fibroblasts.</abstract><cop>United States</cop><pmid>25263961</pmid><doi>10.1016/j.abb.2014.09.013</doi></addata></record> |
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subjects | Angiotensin II - adverse effects Angiotensin II - pharmacology Animals Calcium - metabolism Calcium Signaling Cation Transport Proteins - genetics Cation Transport Proteins - metabolism Endomyocardial Fibrosis - chemically induced Endomyocardial Fibrosis - genetics Endomyocardial Fibrosis - metabolism Endomyocardial Fibrosis - pathology Fibroblasts - metabolism Fibroblasts - pathology Gene Knockdown Techniques Ion Transport - genetics Magnesium - metabolism Muscle Proteins - genetics Muscle Proteins - metabolism Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism NFATC Transcription Factors - genetics NFATC Transcription Factors - metabolism Rats Rats, Sprague-Dawley Vasoconstrictor Agents - adverse effects Vasoconstrictor Agents - pharmacology |
title | SLC41A1 knockdown inhibits angiotensin II-induced cardiac fibrosis by preventing Mg(2+) efflux and Ca(2+) signaling in cardiac fibroblasts |
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