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Propoxyphene Mediates Oxyhemoglobin-Induced Injury in Rat Cortical Neurons Through Up-Regulation of Active-β-Catenin.

丙氧芬通过上调活性-β-Catenin 介导氧合血红蛋白诱导的大鼠皮层神经元损伤。

  • 影响因子:3.92
  • DOI:10.3389/fphar.2019.01616
  • 作者列表:"Li Y","Wang J","Li Z","Cheng H","Zhang Z","Luo T","Zhang X","Gao G","Lu H","Li L
  • 发表时间:2020-01-30
Abstract

:Wnt/β-catenin signaling is involved in various biological processes, including the development of the central nervous system. The dysfunction of mitochondria has been shown to participate in the progress of subarachnoid hemorrhage (SAH). Traumatic subarachnoid hemorrhage (tSAH) is a serious complication in acute craniocerebral trauma. Opioids can activate the canonical Wnt/β-catenin signaling pathway. c-Myc, a downstream protein of Wnt/β-catenin signaling, contributes to the fusion of mitochondria. Here, we investigated the protective roles of Propoxyphene (Pro) against Oxyhemoglobin (OxyHb)-induced primary cultured neuron apoptosis. The data indicated that Pro rescued active-β-catenin from OxyHb-induced decline. Furthermore, Pro attenuated OxyHb-induced apoptosis and fission of mitochondria in primary cortical neurons. However, the protective effects were abrogated under active-β-catenin-deficient conditions. Together, the data presented here showed that Pro, a weak opioid analgesic drug, attenuates OxyHb-induced mitochondria-dependent apoptosis in an active-β-catenin-c-Myc-dependent manner.

摘要

: Wnt/β-catenin 信号参与各种生物学过程,包括中枢神经系统的发育。线粒体功能障碍已被证明参与了蛛网膜下腔出血 (SAH) 的进展。外伤性蛛网膜下腔出血 (tSAH) 是急性颅脑外伤的严重并发症。阿片类药物可激活经典 Wnt/β-catenin 信号通路。C-Myc 是 Wnt/β-catenin 信号的下游蛋白,有助于线粒体的融合。在此,我们研究了丙氧芬 (Pro) 对氧合血红蛋白 (OxyHb) 诱导的原代培养神经元凋亡的保护作用。数据表明,Pro 从 OxyHb 诱导的下降中拯救了活性 β-catenin。此外,Pro 减弱 OxyHb 诱导的原代皮质神经元线粒体凋亡和分裂。然而,在活性 β-catenin 缺乏的条件下,保护作用被消除。总之,这里提出的数据表明,一种弱阿片类镇痛药物 Pro 以活性-β-catenin-c-Myc 依赖性方式减弱 OxyHb 诱导的线粒体依赖性凋亡。

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影响因子:2.57
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DOI:10.1007/s12031-019-01474-x
作者列表:["Cheng, Xiao","Yang, Ying-Lin","Li, Wei-Han","Liu, Man","Zhang, Shan-Shan","Wang, Yue-Hua","Du, Guan-Hua"]

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影响因子:2.75
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DOI:10.1007/s00702-019-02124-7
作者列表:["Wang, Xiaodong","Shi, Cunxian","Pan, Hongxia","Meng, Xiaowen","Ji, Fuhai"]

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