Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Biochem Biophys Res Commun. 2013 Jan 11;430(2):798-803. doi: 10.1016/j.bbrc.2012.11.066. Epub 2012 Nov 29.
Oxidative stress-mediated cell death in cardiomyocytes reportedly plays an important role in many cardiac pathologies. Our previous report demonstrated that mitochondrial SIRT3 plays an essential role in mediating cell survival in cardiac myocytes, and that resveratrol protects cardiomyocytes from oxidative stress-induced apoptosis by activating SIRT3. However, the exact mechanism by which SIRT3 prevents oxidative stress remains unknown. Here, we show that exposure of H9c2 cells to 50 μM H(2)O(2) for 6h caused a significant increase in cell death and the down-regulation of SIRT3. Reactive oxygen species (ROS)-mediated NF-κB activation was involved in this SIRT3 down-regulation. The SIRT3 activator, resveratrol, which is considered an important antioxidant, protected against H(2)O(2)-induced cell death, whereas the SIRT inhibitor, nicotinamide, enhanced cell death. Moreover, resveratrol negatively regulated H(2)O(2)-induced NF-κB activation, whereas nicotinamide enhanced H(2)O(2)-induced NF-κB activation. We also found that SOD2, Bcl-2 and Bax, the downstream genes of NF-κB, were involved in this pathological process. These results suggest that SIRT3 protects cardiomyocytes exposed to oxidative stress from apoptosis via a mechanism that may involve the NF-κB pathway.
据报道，心肌细胞中的氧化应激介导的细胞死亡在许多心脏病理中起着重要作用。我们之前的报告表明，线粒体 SIRT3 在介导心肌细胞存活中起着重要作用，白藜芦醇通过激活 SIRT3 来保护心肌细胞免受氧化应激诱导的细胞凋亡。然而，SIRT3 防止氧化应激的确切机制尚不清楚。在这里，我们表明，将 H9c2 细胞暴露于 50 μM H(2)O(2) 6h 会导致细胞死亡显著增加和 SIRT3 的下调。活性氧 (ROS) 介导的 NF-κB 激活参与了这种 SIRT3 的下调。SIRT3 激活剂白藜芦醇被认为是一种重要的抗氧化剂，可防止 H(2)O(2)诱导的细胞死亡，而 SIRT 抑制剂烟酰胺则增强了细胞死亡。此外，白藜芦醇负调控 H(2)O(2)诱导的 NF-κB 激活，而烟酰胺增强了 H(2)O(2)诱导的 NF-κB 激活。我们还发现，SOD2、Bcl-2 和 Bax，NF-κB 的下游基因，参与了这个病理过程。这些结果表明，SIRT3 通过可能涉及 NF-κB 途径的机制来保护暴露于氧化应激的心肌细胞免于凋亡。
