Endoplasmic Reticulum Stress is Involved in the Neuroprotective Effect of Propofol
Endoplasmic Reticulum Stress is Involved in the Neuroprotective Effect of Propofol
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内质网应激参与异丙酚的神经保护作用
DOI：
10.1007/s11064-014-1369-0
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发表时间：
2014-06
影响因子：
4.4
通讯作者：
Yuxian Shen
中科院分区：
文献类型：
--
作者：
Zhijun Zong;Yiqiao Wang;Lijian Chen;Yuxian Shen
异丙酚是临床上常用的具有抗氧化作用的静脉麻醉药。它被认为在体内和体外都有神经保护作用。然而，潜在的机制仍不清楚。内质网应激在调节细胞死亡和生存的信号通路中起着重要作用。因此，我们想知道异丙酚的神经保护作用是否与其对内质网应激的调节有关。在这项研究中，我们发现异丙酚上调了BiP，并减弱了tunicamycin诱导的神经细胞死亡。异丙酚预处理还能抑制tunicamycin诱导的C/EBP同源蛋白（CHOP）上调。我们还发现，单独使用异丙酚或tunicamycin可增加剪接的XBP1 （XBP1）和裂解的激活转录因子6 （ATF6的一种活性形式）的水平。然而，异丙酚预处理降低了磷酸化的蛋白激酶受体样ER激酶、磷酸化的elF2α、ATF4和caspase-3的水平，但没有影响tunicamycin诱导的裂解的ATF6和XBP1s的增加。用siRNA敲除内源性BiP可消除异丙酚对tunicamycin介导的CHOP和caspase-3活化的抑制作用。同时，敲低BiP降低了异丙酚对暴露于脲霉素的神经细胞的保护作用。这些数据表明，内质网应激通过差异调节未折叠蛋白反应通路参与异丙酚的神经保护作用，其中BiP在启动适应性内质网应激和抑制凋亡性内质网应激中发挥重要作用。
Propofol is a common clinically used intravenous anaesthetic agent with antioxidative property. It has been thought to have neuroprotection in vitro and in vivo. However, the underlying mechanisms remain unclear. Endoplasmic reticulum (ER) stress plays an important role in regulating the signaling pathways concerning cell death and survival. Therefore, we wondered whether the neuroprotective effects of propofol are associated with its regulation on ER stress. In this study, we found that propofol up-regulated BiP and attenuated tunicamycin-induced neural cell death. Propofol pretreatment also inhibited tunicamycin-induced up-regulation of C/EBP homologous protein (CHOP). We also found that propofol or tunicamycin alone increased the levels of spliced XBP1 (XBP1s) and cleaved activating transcription factor 6 (ATF6), an active form of ATF6. However, pretreatment with propofol attenuated the levels of phosphorylated protein kinase receptor-like ER kinase, phosphorylated elF2α, ATF4, and caspase-3, but failed to affect the increase of cleaved ATF6 and XBP1s, induced by tunicamycin. Knockdown endogenous BiP with siRNA abolished the suppression of propofol on tunicamycin-mediated activation of CHOP and caspase-3. Meanwhile, knockdown BiP attenuated the protective effects of propofol on the neural cells exposed to tunicamycin. These data suggest that ER stress is involved in the neuroprotection of propofol via differentially regulating the unfolded protein response pathway, in which BiP plays an important role in initiating the adaptive ER stress and inhibiting the apoptotic ER stress.
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影响因子：
8.8
作者：
L. Velly;B. Guillet;F. Masmejean;A. Nieoullon;N. Bruder;F. Gouin;P. Pisano
通讯作者：
L. Velly;B. Guillet;F. Masmejean;A. Nieoullon;N. Bruder;F. Gouin;P. Pisano
影响因子：
--
作者：
Flori R. Sari;Kenichi Watanabe;B. Widyantoro;R. Thandavarayan;Meilei Harima;Shaosong Zhang;Anthony J. Muslin;M. Kodama;Y. Aizawa
通讯作者：
Flori R. Sari;Kenichi Watanabe;B. Widyantoro;R. Thandavarayan;Meilei Harima;Shaosong Zhang;Anthony J. Muslin;M. Kodama;Y. Aizawa
DOI：
10.1161/01.atv.0000189159.96900.d9
发表时间：
2005-12-01
影响因子：
8.7
作者：
Dickhout, JG;Hossain, GS;Austin, RC
通讯作者：
Austin, RC
DOI：
10.1007/bf03024877
发表时间：
2000-10
期刊：
Canadian Journal of Anesthesia
影响因子：
--
作者：
S. Yamaguchi;S. Hamaguchi;M. Mishio;Y. Okuda;T. Kitajima
通讯作者：
S. Yamaguchi;S. Hamaguchi;M. Mishio;Y. Okuda;T. Kitajima
影响因子：
21.3
作者：
N. Sato;F. Urano;J. Leem;Seong‐Hun Kim;Mingqing Li;D. Donoviel;A. Bernstein;Amy S. Lee;D. Ron;M. Veselits;S. Sisodia;G. Thinakaran
通讯作者：
N. Sato;F. Urano;J. Leem;Seong‐Hun Kim;Mingqing Li;D. Donoviel;A. Bernstein;Amy S. Lee;D. Ron;M. Veselits;S. Sisodia;G. Thinakaran