Lu 2018 Cell Rep

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Lu Z, Cui Y, Wei X, Gao P, Zhang H, Wei X, Li Q, Sun F, Yan Z, Zheng H, Yang G, Liu D, Zhu Z (2018) Deficiency of PKD2L1 (TRPP3) exacerbates pathological cardiac hypertrophy by augmenting NCX1-mediated mitochondrial calcium overload. Cell Rep 24:1639-52.

» PMID: 30089272 Open Access

Lu Zongshi, Cui Yuanting, Wei Xing, Gao Peng, Zhang Hexuan, Wei Xiao, Li Qiang, Sun Fang, Yan Zhencheng, Zheng Hongting, Yang Gangyi, Liu Daoyan, Zhu Zhiming (2018) Cell Rep

Abstract: High salt intake is one independent risk factor for cardiac hypertrophy. Polycystic kidney disease 2-like 1 (PKD2L1, also called TRPP3) acts as a sour sensor in taste cells, and its possible role in the cardiovascular system is unknown. Here, we report that knockout of PKD2L1 exacerbated high-salt diet (HSD)-induced cardiac hypertrophy and fibrosis, accompanied by cardiac dysfunction and reduced cardiac mitochondrial oxidative phosphorylation and enzyme activity. Furthermore, knockdown of PKD2L1 led to more serious mitochondrial Ca2+ overload and reduced Ca2+ uptake in cardiomyocytes on high salt loading. Mechanistically, PKD2L1 deficiency increased p300-mediated acetylation of histone 3 lysine 27 on the promoter of sodium/calcium exchange 1 (NCX1) by repressing AMP-activated protein kinase (AMPK) activity, resulting in NCX1 overexpression and mitochondrial Ca2+ overload. These results reveal an inhibitory effect of PKD2L1 on cardiac hypertrophy and provide a mechanistic insight into the link between mitochondrial Ca2+ homeostasis and cardiac hypertrophy.

Keywords: NCX1, PKD2L1, Cardiac hypertrophy, High-salt diet, Mitochondria Bioblast editor: Kandolf G O2k-Network Lab: CN Chongqing Zhu Z


Labels: MiParea: Respiration, nDNA;cell genetics, Genetic knockout;overexpression, Exercise physiology;nutrition;life style  Pathology: Cardiovascular 

Organism: Mouse  Tissue;cell: Heart  Preparation: Isolated mitochondria 

Regulation: Calcium  Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k 

Labels, 2018-08, CN, Alert2020