Lu 2018 Cell Rep
|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.|
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.
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