Therapeutic inducers of the HSP70/HSP110 protect mice against traumatic brain injury.
Therapeutic inducers of the HSP70/HSP110 protect mice against traumatic brain injury.
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DOI：
10.1111/jnc.12781
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发表时间：
2014-09
影响因子：
4.7
通讯作者：
Mivechi NF
中科院分区：
文献类型：
--
作者：
Eroglu B;Kimbler DE;Pang J;Choi J;Moskophidis D;Yanasak N;Dhandapani KM;Mivechi NF
创伤性脑损伤（TBI）在许多事故受害者和与战斗有关的活动中引起严重的伤害和残疾。热休克蛋白Hsp70/Hsp110保护细胞免于死亡和缺血性损伤。在这项研究中，我们用缺乏Hsp110或Hsp70的小鼠来检测它们在脑外伤后的潜在需求。数据表明，Hsp110或Hsp70的缺失增加了脑损伤和神经元的死亡。在缺乏Hsp110和Hsp70的情况下，TBI后细胞死亡增加的机制之一是ros诱导的p53靶基因Pig1、Pig8和Pig12的表达增加。为了检验提高Hsp70/Hsp110水平的药物是否可以保护细胞免受TBI，我们对小鼠进行了TBI治疗，并给予Celastrol或bp -15。与在TBI和Celastrol治疗后没有保护的Hsp110或hsp70i缺陷小鼠相比，在TBI后第一周给予这些药物后，野生型小鼠有显着改善。此外，神经损伤评估显示，与TBI治疗小鼠相比，在TBI后使用Celastrol或bp -15治疗的野生型小鼠的情境和线索恐惧条件反射测试和束平衡有显著改善。这些研究表明，Hsp70/Hsp110在脑外伤后神经元存活中的重要作用，以及Hsp70/Hsp110诱导剂对减少脑外伤病理后果的有益作用。
Traumatic brain injury (TBI) induces severe harm and disability in many accident victims and combat-related activities. The heat shock proteins Hsp70/Hsp110 protect cells against death and ischemic damage. In this study, we used mice deficient in Hsp110 or Hsp70 to examine their potential requirement following TBI. Data indicate that loss of Hsp110 or Hsp70 increases brain injury and death of neurons. One of the mechanisms underlying the increased cell death observed in the absence of Hsp110 and Hsp70 following TBI is the increased expression of ROS-induced p53 target genes Pig1, Pig8 and Pig12. To examine whether drugs that increase the levels of Hsp70/Hsp110 can protect cells against TBI, we subjected mice to TBI and administered Celastrol or BGP-15. In contrast to Hsp110 or Hsp70i-deficient mice that were not protected following TBI and Celastrol treatment, there was a significant improvement of wild-type mice following administration of these drugs during the first week following TBI. In addition, assessment of neurological injury shows significant improvement of Contextual and Cued Fear Conditioning tests and beam balance in wild-type mice that were treated with Celastrol or BGP-15 following TBI compared to TBI-treated mice. These studies indicate a significant role of Hsp70/Hsp110 in neuronal survival following TBI and the beneficial effects of Hsp70/Hsp110 inducers toward reducing the pathological consequences of TBI.
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影响因子：
4.7
作者：
Laird MD;Sukumari-Ramesh S;Swift AE;Meiler SE;Vender JR;Dhandapani KM
通讯作者：
Dhandapani KM
影响因子：
3.7
作者：
Beck IM;Drebert ZJ;Hoya-Arias R;Bahar AA;Devos M;Clarisse D;Desmet S;Bougarne N;Ruttens B;Gossye V;Denecker G;Lievens S;Bracke M;Tavernier J;Declercq W;Gevaert K;Vanden Berghe W;Haegeman G;De Bosscher K
通讯作者：
De Bosscher K
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
5.3
作者：
Gabai, VL;Mabuchi, K;Sherman, MY
通讯作者：
Sherman, MY
影响因子：
5.3
作者：
Huang, L;Mivechi, NF;Moskophidis, D
通讯作者：
Moskophidis, D