title: Endoplasmic reticulum stress is involved in the neuroprotective effect of propofol.
abstract: 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.
authors: School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
authors: Likui
authors: L
authors: Wang
authors: Weixiang
authors: W
authors: Tang
authors: Tongcui
authors: T
authors: Jiang
authors: Peng
authors: P
authors: Lu
authors: Yuanhai
authors: Y
authors: Li
authors: Aimin
authors: A
authors: Sun
authors: Yujun
authors: Y
authors: Shen
authors: Yin
authors: Y
authors: Chen
authors: Haiping
authors: H
authors: Wang
authors: Zhijun
authors: Z
authors: Zong
authors: Yiqiao
authors: Y
authors: Wang
authors: Lijian
authors: L
authors: Chen
authors: Yuxian
authors: Y
authors: Shen
mesh_terms: D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D014415:Tunicamycin / Q000494:pharmacology; D056811:Unfolded Protein Response / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018696:Neuroprotective Agents; D014415:Tunicamycin; D015742:Propofol