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Resistance to pathologic cardiac hypertrophy and reduced expression of CaV1.2 in Trpc3-depleted mice

Authors
 Jung Woo Han  ;  Young Ho Lee  ;  Su-In Yoen  ;  Joel Abramowitz  ;  Lutz Birnbaumer  ;  Min Goo Lee  ;  Joo Young Kim 
Citation
 Molecular and Cellular Biochemistry, Vol.421(1~2) : 55-65, 2016 
Journal Title
 Molecular and Cellular Biochemistry 
ISSN
 0300-8177 
Issue Date
2016
MeSH
Animals ; Calcium Channels, L-Type/biosynthesis* ; Calcium Channels, L-Type/genetics ; Calcium Signaling* ; Cardiomegaly/genetics ; Cardiomegaly/metabolism* ; Cardiomegaly/pathology ; Gene Expression Regulation* ; Mesenteric Arteries/metabolism ; Mesenteric Arteries/pathology ; Mice ; Mice, Knockout ; Myocardium/metabolism* ; Myocardium/pathology ; Phenylephrine/metabolism ; TRPC Cation Channels/deficiency* ; Vasoconstriction/genetics
Keywords
Ca2+ influx ; L-type Ca2+ channel ; Pathologic cardiac hypertrophy ; Transient receptor potential canonical channels 3
Abstract
Sustained elevation of intracellular Ca(2+) concentration ([Ca(2+)]i) reprograms cardiovascular cell fate, leading to cellular hypertrophy via Ca(2+)-calmodulin/calcineurin (Cn)/NFAT activation. Accumulating evidence suggests that transient receptor potential canonical (Trpc) channels play important roles in the development of pathologic cardiac hypertrophy. Here, we demonstrated that Trpc3 mediates pathologic cardiac hypertrophy in neurohumoral elevation via direct regulation of CaV1.2 expressions. Elevated PE (phenylephrine) was maintained in mice by continuous infusion using an osmotic pump. Wild-type (WT) mice, but not Trpc3 (-/-) showed a sudden decrease in blood pressure (BP) or death following elevation of BP under conditions of elevated PE. Trpc3 (-/-) mesenteric artery showed decreased PE-stimulated vasoconstriction. Analysis of morphology, function, and pathologic marker expression revealed that PE elevation caused pathologic cardiac hypertrophy in WT mice, which was prevented by deletion of Trpc3. Interestingly, protection by Trpc3 deletion seemed to be a result of reduced cardiac CaV1.2 expressions. Basal and PE induced increased expression of protein and mRNA of CaV1.2 was decreased in Trpc3 (-/-) heart. Accordingly, altered expression of CaV1.2 was observed by knockdown or stimulation of Trpc3 in cardiomyocytes. These findings suggest that Trpc3 is a mediator of pathologic cardiac hypertrophy not only through mediating part of the Ca(2+) influx, but also through control of CaV1.2 expressions.
Full Text
https://link.springer.com/article/10.1007%2Fs11010-016-2784-0
DOI
10.1007/s11010-016-2784-0
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실)
Yonsei Authors
김주영(Kim, Joo Young) ORCID logo https://orcid.org/0000-0003-2623-1491
이민구(Lee, Min Goo) ORCID logo https://orcid.org/0000-0001-7436-012X
이영호(Lee, Young Ho) ORCID logo https://orcid.org/0000-0002-5749-1045
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/152000
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