Resveratrol mimics ischemic preconditioning in the brain
Resveratrol mimics ischemic preconditioning in the brain
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DOI：
10.1038/sj.jcbfm.9600262
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发表时间：
2006-09-01
影响因子：
6.3
通讯作者：
Perez-Pinzon, Miguel A.
中科院分区：
文献类型：
--
作者：
Raval, Ami P.;Dave, Kunjan R.;Perez-Pinzon, Miguel A.
最近在包括哺乳动物在内的多种物种中的研究表明，白藜芦醇（反式-3，5，4”-三羟基芪）处理和热量限制增加沉默信息调节因子2/沉默调节蛋白1活性，其介导寿命/细胞存活的增加。白藜芦醇是一种天然存在的植物抗毒素，也是一种有据可查的心脏保护剂。类似地，缺血预处理（IPC）已被证明对随后的缺血性损伤具有心脏和脑保护作用。这一领域的一个主要重点是了解介导这种现象的分子机制。本研究的目的是确定白藜芦醇是否可以模仿IPC对脑缺血的神经保护作用。采用脑缺血的体外模型，器官型海马脑片培养，我们报告，白藜芦醇预处理模拟IPC通过SIRT 1途径。IPC或白藜芦醇预处理后，sirtinol阻断SIRT 1的激活，可消除其神经保护作用。更好地了解白藜芦醇以预防性方式诱导缺血耐受的机制可能会为中风或神经外科手术提供新的治疗方法。
Recent studies in a variety of species including mammals showed that resveratrol (trans-3, 5, 4"-trihydroxystibene) treatment and caloric restriction increased silent information regulator 2/sirtuin 1 activity, which mediated increase in life span/cell survival. Resveratrol is a naturally occurring phytoalexin and a well-documented cardioprotective agent. Similarly, ischemic preconditioning (IPC) has been shown to be both cardio- and cerebroprotective against subsequent ischemic insults. A major emphasis in this field is to understand the molecular mechanisms that mediate this phenomenon. The goal of this study was to define whether resveratrol can emulate IPC neuroprotection against cerebral ischemia. Employing an in vitro model of cerebral ischemia, the organotypic hippocampal slice culture, we report that resveratrol pretreatment mimics IPC via the SIRT1 pathway. Blockade of SIRT1 activation by sirtinol after IPC or resveratrol pretreatment abolished their neuroprotection. A better understanding of the mechanisms by which resveratrol induces ischemic tolerance in a prophylactic manner may provide a novel therapy against stroke or neurosurgical procedures.