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KMID : 1034820190150030297
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Molecular & Cellular Toxicology
2019 Volume.15 No. 3 p.297 ~ p.305
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Mild NO preconditioning protects H9c2 cells against NO-induced apoptosis through activation of PI3K/Akt and PKA-dependent pathways
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Kwak Hyun-Jeong
Um Jae-Young
Lee Sang-Seob
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Abstract
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Backgrounds: Nitric oxide (NO) plays a key role in cardioprotection. Its role against cardioprotection is dependent on the level of NO. Although it is well known that NO preconditioning has cardioprotective effects, but its mechanism remains unsatisfactory.
Methods: To induce NO preconditioning, H9c2 cells were treated with low NO concentration and subsequently induced apoptosis by high NO. The signalling and anti-apoptotic effects of NO preconditioning were monitored by Western blotting, facs analysis.
Results: Sodium nitroprusside (SNP)-induced cytotoxicity was inhibited by low SNP (0.3 mM) preconditioning. Furthermore, low SNP phosphorylated Akt/FoxO1 in the presence of high SNP (1.5 mM), while phosphorylated Akt/FoxO1 and viability were reversed by PI3K inhibitor. Also, low NO-induced CREB phosphorylation with high NO was inhibited by PKA inhibitor, indicating that NO preconditioning protects NO-induced cytotoxicity in PKA dependently. Apoptotic inhibition with NO preconditioning was accompanied with increased Bcl-2, decreased Bax, and caspase3 activation, which was all reversed by LY294002.
Conclusion: Our results indicate that low NO preconditioning prevent subsequent high NO-induced apoptosis via Akt/PKA/CREB activation in H9c2 cells.
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KEYWORD
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Cardioprotection, Ischemia/Reperfusion, Preconditioning, Nitric oxide
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