Resveratrol pretreatment protects rat brain from cerebral ischemic damage via a sirtuin 1-uncoupling protein 2 pathway.
Resveratrol pretreatment protects rat brain from cerebral ischemic damage via a sirtuin 1-uncoupling protein 2 pathway.
复制标题
DOI：
10.1016/j.neuroscience.2009.01.017
复制
发表时间：
2009-03-31
期刊：
影响因子：
3.3
通讯作者：
Perez-Pinzon, M. A.
中科院分区：
文献类型：
--
作者：
Della-Morte, D.;Dave, K. R.;Defazio, R. A.;Bao, Y. C.;Raval, A. P.;Perez-Pinzon, M. A.
白藜芦醇是葡萄和葡萄酒中发现的一种天然多酚，具有预防心血管疾病的作用。白藜芦醇预处理（RPC）和缺血预处理（IPC）均需要激活sirtuin 1（SIRT 1），一种NAD+依赖性脱乙酰酶，以诱导对脑缺血的神经保护作用。在本研究中，我们测试了两个假设：a）RPC可以在体内诱导针对脑缺血的神经保护;以及B）RPC神经保护涉及通过SIRT 1靶向线粒体解偶联蛋白2（UCP 2）改变线粒体功能。IPC通过两分钟的全脑缺血（暂时性双侧颈动脉闭塞伴低血压）诱导，RPC通过腹膜内注射10、50和100 mg/Kg剂量的白藜芦醇诱导。48小时后，我们比较了RPC和IPC的神经保护作用，在脆弱的CA 1海马锥体神经元使用窒息心脏骤停（ACA）大鼠模型。使用SIRT 1特异性荧光酶活性测定来测量SIRT 1活性。在IPC或RPC后48小时分离的海马线粒体中，我们测量了UCP 2水平、膜电位、呼吸和线粒体ATP合成效率（ADP/O比）。在该体内模型中，IPC和RPC均诱导对心脏骤停诱导的脑损伤的耐受。IPC在处理后48小时增加海马SIRT 1活性，而RPC在处理后1小时增加SIRT 1活性，但不增加48小时。白藜芦醇显著降低UCP 2水平的35%相比，假治疗的大鼠。SIRT 1特异性抑制剂sirtinol消除了RPC提供的神经保护作用和UCP 2水平的降低。RPC还能显著增加海马线粒体ADP/O比值，反映ATP合成效率的提高。总之，体内白藜芦醇预处理通过SIRT 1-UCP 2途径赋予与IPC相似的神经保护作用。
Resveratrol is a natural polyphenol found in grapes and wine and has been associated with protective effects against cardiovascular diseases. In vitro, both resveratrol preconditioning (RPC) and ischemic preconditioning (IPC) require activation of sirtuin 1 (SIRT1), an NAD+-dependent deacetylases, to induce neuroprotection against cerebral ischemia. In the present study, we tested two hypotheses: a) that neuroprotection against cerebral ischemia can be induced by RPC in vivo; and b) that RPC neuroprotection involves alterations in mitochondrial function via the SIRT1 target mitochondrial uncoupling protein 2 (UCP2). IPC was induced by two minutes of global ischemia (temporary bilateral carotid artery occlusion with hypotension), and RPC, by intraperitoneal injection of resveratrol at 10, 50 and 100 mg/Kg dosages. 48 hours later, we compared the neuroprotective efficacy of RPC and IPC in vulnerable CA1 hippocampal pyramidal neurons using a rat model of asphyxial cardiac arrest (ACA). SIRT1 activity was measured using a SIRT1-specific fluorescent enzyme activity assay. In hippocampal mitochondria isolated 48 hours after IPC or RPC, we measured UCP2 levels, membrane potential, respiration, and the mitochondrial ATP synthesis efficiency (ADP/O ratio). Both IPC and RPC induced tolerance against brain injury induced by cardiac arrest in this in vivo model. IPC increased SIRT1 activity at 48 hours, while RPC increased SIRT1 activity at 1 hour but not 48 hours after treatment in hippocampus. Resveratrol significantly decreased UCP2 levels by 35% compared to sham-treated rats. The SIRT1-specific inhibitor sirtinol abolished the neuroprotection afforded by RPC and the decrease in UCP2 levels. Finally, RPC significantly increased the ADP/O ratio in hippocampal mitochondria reflecting enhanced ATP synthesis effieciency. In conclusion, in vivo resveratrol pretreatment confers neuroprotection similar to IPC via the SIRT1-UCP2 pathway.
登录
查看更多内容
影响因子：
9.8
作者：
Bordone L;Motta MC;Picard F;Robinson A;Jhala US;Apfeld J;McDonagh T;Lemieux M;McBurney M;Szilvasi A;Easlon EJ;Lin SJ;Guarente L
通讯作者：
Guarente L
影响因子：
5.3
作者：
Dave, Kunjan R.;DeFazio, R. Anthony;Perez-Pinzon, Miguel A.
通讯作者：
Perez-Pinzon, Miguel A.
影响因子：
4.8
作者：
Pecqueur, C;Alves-Guerra, MC;Miroux, B
通讯作者：
Miroux, B
影响因子：
82.9
作者：
Mattiasson, G;Shamloo, M;Wieloch, T
通讯作者：
Wieloch, T
影响因子：
6.3
作者：
Deierborg, Tomas;Wieloch, Tadeusz;Mattiasson, Gustav
通讯作者：
Mattiasson, Gustav