期刊
SCIENTIFIC REPORTS
卷 7, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/srep45379
关键词
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资金
- National Key Basic Research Program of China [2013CB531203, 2014CB542206]
- National Science Foundation of China [31371350, 81670233]
Protein tyrosine phosphatase interacting protein 51 (PTPIP51) participates in multiple cellular processes, and dysfunction of PTPIP51 is implicated in diseases such as cancer and neurodegenerative disorders. However, there is no functional evidence showing the physiological or pathological roles of PTPIP51 in the heart. We have therefore investigated the role and mechanisms of PTPIP51 in regulating cardiac function. We found that PTPIP51 was markedly upregulated in ischemia/reperfusion heart. Upregulation of PTPIP51 by adenovirus-mediated overexpression markedly increased the contact of mitochondria-sarcoplasmic reticulum (SR), elevated mitochondrial Ca2+ uptake from SR release through mitochondrial ca(2+) uniporter. Inhibition or knockdown of mitochondrial Ca2+ uniporter reversed PTPIP51-mediated increase of mitochondrial Ca2+ and protected cardiomyocytes against PTPIP51-mediated apoptosis. More importantly, cardiac specific knockdown of PTPIP51 largely reduced myocardium infarction size and heart injury after ischemia/reperfusion. Our study defines a novel and essential function of PTPIP51 in the cardiac ischemia/reperfusion process by mediating mitochondria-SR contact. Downregulation of PTPIP51 improves heart function after ischemia/reperfusion injury, suggesting PTPIP51 as a therapeutic target for ischemic heart diseases.
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