| First Author | Zhu K | Year | 2024 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1870 |
| Issue | 7 | Pages | 167318 |
| PubMed ID | 38909849 | Mgi Jnum | J:350428 |
| Mgi Id | MGI:7663012 | Doi | 10.1016/j.bbadis.2024.167318 |
| Citation | Zhu K, et al. (2024) p85alpha deficiency alleviates ischemia-reperfusion injury by promoting cardiomyocyte survival. Biochim Biophys Acta Mol Basis Dis 1870(7):167318 |
| abstractText | Myocardial ischemia-reperfusion (I/R) injury is a prevalent cause of myocardial injury, involving a series of interconnected pathophysiological processes. However, there is currently no clinical therapy for effectively mitigating myocardial I/R injury. Here, we show that p85alpha protein levels increase in response to I/R injury through a comprehensive analysis of cardiac proteomics, and confirm this in the I/R-injured murine heart and failing human myocardium. Genetic inhibition of p85alpha in mice activates the Akt-GSK3beta/Bcl-x(L) signaling pathway and ameliorates I/R-induced cardiac dysfunction, apoptosis, inflammation, and mitochondrial dysfunction. p85alpha silencing in cardiomyocytes alleviates hypoxia-reoxygenation (H/R) injury through activating the Akt-GSK3beta/Bcl-x(L) signaling pathway, while its overexpression exacerbates the damage. Mechanistically, the interaction between MG53 and p85alpha triggers the ubiquitination and degradation of p85alpha, consequently enhancing Akt phosphorylation and ultimately having cardioprotective effects. Collectively, our findings reveal that substantial reduction of p85alpha and subsequently activated Akt signaling have a protective effect against cardiac I/R injury, representing an important therapeutic strategy for mitigating myocardial damage. |
