The neuroprotective effects of Tanshinone IIA are associated with induced nuclear translocation of TORC1 and upregulated expression of TORC1, pCREB and BDNF in the acute stage of ischemic stroke
The neuroprotective effects of Tanshinone IIA are associated with induced nuclear translocation of TORC1 and upregulated expression of TORC1, pCREB and BDNF in the acute stage of ischemic stroke
复制标题
丹参酮 IIA 的神经保护作用与缺血性中风急性期 TORC1 的诱导核转位以及 TORC1、pCREB 和 BDNF 表达上调有关
DOI：
10.1016/j.brainresbull.2010.04.005
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发表时间：
2010-05-31
影响因子：
3.8
通讯作者：
Wang, Shan
中科院分区：
文献类型：
--
作者：
Liu, Lingling;Zhang, Xiangjian;Wang, Shan
cAMP反应元件结合蛋白（CREB）的激活和CREB靶基因的转录在各种生理和病理条件下起着关键作用。调节CREB活性的转导子（TORC）代表了一个新的保守CREB共激活子家族，可促进CREB靶向基因的激活。丹参酮HA（Tanshinone HA，TSA）已被证实对脑缺血损伤具有保护作用。然而，对潜在的机制知之甚少。在此，我们检测了缺血性卒中早期以及TSA治疗后TORC 1（调节CREB活性的转导子1）的活性依赖性核转位以及TORC 1、磷酸化CREB（pCREB）和BDNF（脑源性神经营养因子）的表达。我们观察到pCREB，TORC 1和BDNF蛋白水平的双峰增加和TORC 1在缺血急性期的瞬时核积累。TSA（20 mg/kg）可显著降低大鼠神经功能缺损评分、脑含水量和脑梗死面积，增加TORC 1在核内的聚集，上调TORC 1、pCREB和BDNF的表达（P
The activation of cAMP response element binding protein (CREB) and transcription of CRE-targeted genes play critical roles in various physiological and pathological conditions. Transducers of regulated CREB activity (TORCs) represent a new family of conserved CREB coactivators that promote the activation of CRE-targeted genes. Tanshinone HA (TSA) has been proven to protect the brain against focal ischemia injury. However, little is known regarding the underlying mechanisms. Herein, we examined the activity-dependent nuclear translocation of TORC1 (transducer of regulated CREB activity 1) and the expression of TORC1, phosphorylated CREB (pCREB) and BDNF (brain-derived neurotrophic factor) at the early time of ischemic stroke as well as after the treatment with TSA. We observed a bimodal increase in pCREB,TORC1 and BDNF protein levels and transient nuclear accumulation of TORC1 in the acute stage of ischemia. Compared with vehicle group, TSA (20 mg/kg) dramatically lessened neurological deficits scores, brain water contents and infarct sizes, significantly enhanced nuclear accumulation of TORC1 and upregulated the expression of TORC1, pCREB and BDNF (P