SIRT1/PGC-1α Signaling Promotes Mitochondrial Functional Recovery and Reduces Apoptosis after Intracerebral Hemorrhage in Rats.
SIRT1/PGC-1α Signaling Promotes Mitochondrial Functional Recovery and Reduces Apoptosis after Intracerebral Hemorrhage in Rats.
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DOI：
10.3389/fnmol.2017.00443
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发表时间：
2017
影响因子：
4.8
通讯作者：
Zhao Y
中科院分区：
文献类型：
--
作者：
Zhou Y;Wang S;Li Y;Yu S;Zhao Y
沉默信息调节因子1（SIRT 1）在许多神经退行性疾病中发挥神经保护作用。然而，目前尚不清楚SIRT 1是否对脑出血（ICH）诱导的大鼠脑损伤具有保护作用。因此，我们的目标是研究SIRT 1对ICH损伤的影响以及这种影响的任何潜在机制。通过向大鼠脑内注射自体动脉血（60 μL）诱导脑损伤，数据显示，用SRT 1720（5 mg/kg）激活SIRT 1可恢复核SIRT 1、PGC-1α的脱乙酰化和线粒体生物合成，并降低死亡率、行为缺陷和脑含水量，而ICH诱导的磷酸化AMP激活蛋白激酶（pAMPK）无显著变化。SRT 1720激活SIRT 1也恢复了ICH中线粒体电子传递链蛋白并减少了凋亡蛋白;然而，这些变化在ICH后被逆转。相反，用PGC-1α siRNA处理产生相反的效果。为了探索SIRT 1在ICH后的保护作用，使用siRNA敲低SIRT 1。SIRT 1 siRNA治疗增加了ICH后的死亡率、行为缺陷、脑含水量、线粒体功能障碍和神经细胞凋亡。因此，SIRT 1的激活通过增加线粒体生物合成促进线粒体蛋白和功能的恢复，并通过PGC-1α线粒体途径减少ICH后的细胞凋亡。这些数据可能为ICH损伤提供新的治疗方法。
Silent information regulator 1 (SIRT1) exerts neuroprotection in many neurodegenerative diseases. However, it is not clear if SIRT1 has protective effects after intracerebral hemorrhage (ICH)-induced brain injury in rats. Thus, our goal was to examine the influence of SIRT1 on ICH injuries and any underlying mechanisms of this influence. Brain injury was induced by autologous arterial blood (60 μL) injection into rat brains, and data show that activation of SIRT1 with SRT1720 (5 mg/kg) restored nuclear SIRT1, deacetylation of PGC-1α, and mitochondrial biogenesis and decreased mortality, behavioral deficits, and brain water content without significant changes in phosphorylated AMP-activated protein kinase (pAMPK) induced by ICH. Activation of SIRT1 with SRT1720 also restored mitochondrial electron transport chain proteins and decreased apoptotic proteins in ICH; however, these changes were reversed after ICH. In contrast, treatment with PGC-1α siRNA yielded opposite effects. To explore the protective effects of SIRT1 after ICH, siRNAs were used to knockdown SIRT1. Treatment with SIRT1 siRNA increased mortality, behavioral deficits, brain water content, mitochondrial dysfunction, and neurocyte apoptosis after ICH. Thus, activation of SIRT1 promotes recovery of mitochondrial protein and function by increasing mitochondrial biogenesis and reduces apoptosis after ICH via the PGC-1α mitochondrial pathway. These data may suggest a new therapeutic approach for ICH injuries.
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影响因子：
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作者：
Otera H;Mihara K
通讯作者：
Mihara K
影响因子：
11.2
作者：
Ma, Qingyi;Chen, Sheng;Hu, Qin;Feng, Hua;Zhang, John H.;Tang, Jiping
通讯作者：
Tang, Jiping
影响因子：
11.4
作者：
Kim, Dohoon;Nguyen, Minh Dang;Tsai, Li-Huei
通讯作者：
Tsai, Li-Huei
影响因子：
4.7
作者：
Makela, Johanna;Tselykh, Timofey V.;Lindholm, Dan
通讯作者：
Lindholm, Dan
DOI：
10.1016/s1474-4422(12)70104-7
发表时间：
2012-08
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Keep RF;Hua Y;Xi G
通讯作者：
Xi G