Molecular mechanism underlying Akt activation in zinc-induced cardioprotection.

摘要: Our previous study demonstrated that zinc prevents cardiac reperfusion injury by targeting the mitochondrial permeability transition pore (mPTP) via Akt and glycogen synthetase kinase 3beta (GSK-3beta). We aimed to address mechanism which activates Akt. Treatment of H9c2 cells with ZnCl(2) (10 microM) in presence ionophore pyrithione (4 for 20 min enhanced phosphorylation (Ser(473)), indicating can rapidly activate Zinc did not alter either phosphatase tensin homolog deleted on chromosome 10 (PTEN) total PTEN protein levels or oxidation, implying may play a role action zinc. However, zinc-induced was blocked both nonselective receptor tyrosine (RTK) inhibitor genistein selective insulin-like growth factor-1 RTK (IGF-1RTK) AG1024, IGF-1RTK. Zinc-induced Ser/Thr also abolished AG1024. In addition, markedly IGF-1 (IGF-1R), again reversed A confocal imaging revealed AG1024 preventive effect oxidant-induced mPTP opening, confirming IGF-1RTK plays cardioprotection. Furthermore, decreased activity 2A (PP2A), major phosphatase, phosphatases activity. Taken together, these findings demonstrate exogenous opening cells. Inactivation contribute activation.