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
Hauptverfasser: Yu, Na, Jiang, Jianmin, Yu, Yang, Li, Hong, Huang, Xiaoyang, Ma, Yunzi, Zhang, Luankun, Zou, Jian, Zhang, Boyu, Chen, Shaorui, Liu, Peiqing
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container_title Archives of biochemistry and biophysics
container_volume 564
creator Yu, Na
Jiang, Jianmin
Yu, Yang
Li, Hong
Huang, Xiaoyang
Ma, Yunzi
Zhang, Luankun
Zou, Jian
Zhang, Boyu
Chen, Shaorui
Liu, Peiqing
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.
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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. 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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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