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Published on: January 10, 2025
Resveratrol relieves myocardial ischemia-reperfusion injury through inhibiting AKT nitration modification
Lei Li1, Jiantao Wang1, Dandan Zhang1
1Department of General Practice, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People's Republic of China.
Objective:
The aim of this study was to clarify whether Protein kinase B (PKB)/AKT is nitrated in myocardial ischemia and reperfusion injury (MIRI) resveratrol (RSV)'s protective effect during this process.
Methods:
We blocked blood flow of the left coronary artery (LAD) of mice and used H9c2 cells under an oxygen-glucose deprivation (OGD) environment as animal and cell models of MIRI. N-methyl-D-aspartic acid receptor (NMDAR) inhibitor MK801, neuronal nitric oxide synthase (nNOS) inhibitor 7-NI and RSV were used as interventions. Nitration of proteins, infarction area, cardiomyocyte apoptosis and AKT nitration sites were detected during this study.
Results:
During in-vivo study, AKT nitration was induced through the NMDAR/nNOS/peroxynitrite (ONOO-) pathway, leading to decreased phosphorylation of AKT and increased cardiomyocyte apoptosis. AKT nitration was decreased and phosphorylation was elevated when administrated with RSV, MK801 and 7-NI. In in-vitro study, AKT nitration and TUNEL positive cells was elevated when administrated with NO donor H9c2 cells after OGD/R, when administrated with RSV, MK801 and 7-NI, AKT nitration and apoptosis was deceased in H9c2 cells. Mass spectrometry revealed that nitration sites of AKT included 14 Tyrosine residues.
Discussion:
RSV could inhibit AKT nitration and elevated phosphorylation through suppressing NMDAR/nNOS/ONOO- pathway and further reduce the apoptosis of cardiomyocytes in of myocardial I/R.
