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 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 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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536672 | PMC |
http://dx.doi.org/10.1080/13510002.2024.2420564 | DOI Listing |
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