| First Author | Lu Z | Year | 2018 |
| Journal | Cell Rep | Volume | 24 |
| Issue | 6 | Pages | 1639-1652 |
| PubMed ID | 30089272 | Mgi Jnum | J:270725 |
| Mgi Id | MGI:6278664 | Doi | 10.1016/j.celrep.2018.07.022 |
| Citation | Lu Z, et al. (2018) Deficiency of PKD2L1 (TRPP3) Exacerbates Pathological Cardiac Hypertrophy by Augmenting NCX1-Mediated Mitochondrial Calcium Overload. Cell Rep 24(6):1639-1652 |
| abstractText | 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 Ca(2+) overload and reduced Ca(2+) 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 Ca(2+) overload. These results reveal an inhibitory effect of PKD2L1 on cardiac hypertrophy and provide a mechanistic insight into the link between mitochondrial Ca(2+) homeostasis and cardiac hypertrophy. |
