Potential neuroprotective effects of SIRT1 induced by glucose deprivation in PC12 cells
Potential neuroprotective effects of SIRT1 induced by glucose deprivation in PC12 cells
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DOI：
10.1016/j.neulet.2013.10.050
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发表时间：
2013-12-17
影响因子：
2.5
通讯作者：
Nedachi, Taku
中科院分区：
文献类型：
--
作者：
Fujino, Kotaro;Ogura, Yurina;Nedachi, Taku
营养物质可用性是调节细胞命运（包括细胞生长、分化和死亡）的最重要信号之一。最近的证据表明，NAD(+) 依赖性组蛋白脱乙酰酶 Sirtuin 1 (SIRT1) 在将营养可用性变化与细胞命运调节联系起来方面发挥着重要作用。 SIRT1 在神经元中表达，但该蛋白的表达和功能调节尚不完全清楚。在本研究中，我们检查了细胞外葡萄糖浓度是否影响 PC12 细胞中 SIRT1 的表达和定位。此外，我们检查了叉头框 O3a (FoxO3a) 的水平，它也受到细胞外葡萄糖浓度变化的控制。我们观察到，当通过基因表达控制增加葡萄糖利用率时，PC12 细胞中 SIRT1 和 FoxO3a 的总表达水平降低（至少部分降低）。 SIRT1 和 FoxO3a 的核定位因葡萄糖剥夺而增加。尽管细胞外葡萄糖浓度的变化以相似的方向调节SIRT1和FoxO3a，但神经生长因子对这两种蛋白的影响完全不同。最后，我们发现有效的 SIRT1 抑制剂可增强葡萄糖剥夺诱导的细胞死亡。因此，我们认为葡萄糖剥夺诱导的 SIRT1 表达可能在保护 PC12 细胞中发挥重要作用。 (C) 2013 Elsevier Ireland Ltd. 保留所有权利。
Nutrient availability is one of the most important signals regulating cellular fates including cell growth, differentiation, and death. Recent evidence suggests that the NAD(+)-dependent histone deacetylase sirtuin 1 (SIRT1) plays a prominent role in linking changes in nutritional availability with cellular fate regulation. SIRT1 expression is observed in neurons, yet the expressional and functional regulation of this protein is not fully understood. In the present study, we examined whether extracellular glucose concentration affects the expression and localization of SIRT1 in PC12 cells. Further, we examined levels of forkhead box O3a (FoxO3a), which is also controlled by changes in extracellular glucose concentration. We observed the total expression levels of SIRT1 and FoxO3a in PC12 cells were reduced when glucose availability increased via gene expressional control, at least in part. Nuclear localization of SIRT1 and FoxO3a was increased by glucose deprivation. Even though the changes in extracellular glucose concentration regulated SIRT1 and FoxO3a in a similar direction, the effects of nerve growth factor on these two proteins were completely different. Finally, we found the potent SIRT1 inhibitor enhanced glucose deprivation-induced cell death. Therefore, we propose that glucose deprivation-induced SIRT1 expression potentially plays a major role in protecting PC12 cells. (C) 2013 Elsevier Ireland Ltd. All rights reserved.