Premium
Notch1 provides myocardial protection by improving mitochondrial quality control
Author(s) -
Zhou XueLiang,
Wu Xia,
Xu QiRong,
Zhu RongRong,
Xu Hua,
Li YunYun,
Liu Sheng,
Huang Huang,
Xu Xinping,
Wan Li,
Wu QiCai,
Liu JiChun
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27892
Subject(s) - pink1 , mfn2 , mitophagy , mitochondrial fission , mitochondrial fusion , gene knockdown , mitochondrion , microbiology and biotechnology , viability assay , parkin , mitochondrial ros , mitochondrial dna , chemistry , apoptosis , biology , medicine , autophagy , biochemistry , gene , disease , parkinson's disease
Abstract Mitochondrial quality control is a new target for myocardial protection. Notch signaling plays an important role in heart development, maturation, and repair. However, the role of Notch in the myocardial mitochondrial quality control remains elusive. In this study, we isolated myocardial cells from rats and established myocardial ischemia reperfusion injury (IRI) model. We modulated Notch1 expression level in myocardial cells via infection with recombinant adenoviruses Ad‐N1ICD and Ad‐shN1ICD. We found that IR reduced myocardial cells viability, but Notch1 overexpression increased the viability of myocardial cells exposed to IRI. In addition, Notch1 overexpression improved ATP production, increased mitochondrial fusion and decreased mitochondrial fission, and inhibited mitophagy in myocardial cells exposed to IRI. However, N1ICD knockdown led to opposite effects. The myocardial protection role of Notch1 was related to the inhibition of Pink1 expression and Mfn2 and Parkin phosphorylation. In conclusion, Notch1 exerts myocardial protection and this is correlated with the maintenance of mitochondrial quality control and the inhibition of Pink1/Mfn2/Parkin signaling.