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Cardiac Na^(+)-Ca^(2+) exchanger 1(ncx1h)is critical for the ventricular cardiomyocyte formation via regulating the expression levels of gata4 and hand2 in zebrafish 被引量:3
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作者 Liming Chu Huimin Yin +9 位作者 Lei Gao Li Gao Yu Xia Chiyuan Zhang Yi Chen Tingxi Liu Jijun Huang Kenneth R.Boheler Yong Zhou Huang-Tian Yang 《Science China(Life Sciences)》 SCIE CAS CSCD 2021年第2期255-268,共14页
Ca^(2+) signaling is critical for heart development;however,the precise roles and regulatory pathways of Ca^(2+) transport proteins in cardiogenesis remain largely unknown.Sodium-calcium exchanger 1(Ncx1)is responsibl... Ca^(2+) signaling is critical for heart development;however,the precise roles and regulatory pathways of Ca^(2+) transport proteins in cardiogenesis remain largely unknown.Sodium-calcium exchanger 1(Ncx1)is responsible for Ca^(2+) efflux in cardiomyocytes.It is involved in cardiogenesis,while the mechanism is unclear.Here,using the forward genetic screening in zebrafish,we identified a novel mutation at a highly-conserved leucine residue in ncx1 gene(mutant^(LDD353)/ncx1h^(L154P))that led to smaller hearts with reduced heart rate and weak contraction.Mechanistically,the number of ventricular but not atrial cardiomyocytes was reduced in ncx1h^(L154P) zebrafish.These defects were mimicked by knockdown or knockout of ncx1h.Moreover,ncx1h^(L154P) had cytosolic and mitochondrial Ca^(2+) overloading and Ca^(2+) transient suppression in cardiomyocytes.Furthermore,ncx1h^(L154P) and ncx1h morphants downregulated cardiac transcription factors hand2 and gata4 in the cardiac regions,while overexpression of hand2 and gata4 partially rescued cardiac defects including the number of ventricular myocytes.These findings demonstrate an essential role of the novel 154th leucine residue in the maintenance of Ncx1 function in zebrafish,and reveal previous unrecognized critical roles of the 154th leucine residue and Ncx1 in the formation of ventricular cardiomyocytes by at least partially regulating the expression levels of gata4 and hand2. 展开更多
关键词 ncx1h Ca^(2+)transport protein ventricular cardiomyocyte formation hand2 GATA4 ZEBRAFISH
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