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Phoenixin 14 inhibits ischemia/reperfusion-induced cytotoxicity in microglia.
Archives of Biochemistry and Biophysics ( IF 3.8 ) Pub Date : 2020-05-23 , DOI: 10.1016/j.abb.2020.108411
Hongling Ma 1 , Daoqing Su 2 , Qingdong Wang 1 , Zonglei Chong 2 , Qiushi Zhu 2 , Weibin He 3 , Wei Wang 1
Affiliation  

The process of ischemia/reperfusion (IR) in ischemic stroke often leads to significant cell death and permanent neuronal damage. Safe and effective treatments are urgently needed to mitigate the damage caused by IR injury. The naturally occurring pleiotropic peptide phoenixin 14 (PNX-14) has recently come to light as a potential treatment for IR injury. In the present study, we examined the effects of PNX-14 on several key processes involved in ischemic injury, such as pro-inflammatory cytokine expression, oxidative stress, and the related cascade mediated through the toll-like receptor 4 (TLR4) pathway, using BV2 microglia exposed to oxygen-glucose deprivation and reoxygenation (OGD/R). Our results demonstrate an acute ability of PNX-14 to regulate the expression levels of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). PNX-14 also prevented oxidative stress by reducing the generation of reactive oxygen species (ROS) and increasing the level of the antioxidant glutathione (GSH). Importantly, PNX-14 inhibited high-mobility group box 1 (HMGB1)/TLR4/myeloid differentiation primary response 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway, by inhibiting the activation of TLR4 and preventing the nuclear translocation of p65 protein. We further confirmed the cerebroprotective effects of PNX-14 in an MCAO rat model, which resulted in reduced infarct volume and decreased microglia activation. Together, the results of this study implicate a possible protective role of PNX-14 against various aspects of IR injury in vitro.



中文翻译:

Phoenixin 14抑制小胶质细胞的缺血/再灌注诱导的细胞毒性。

缺血性中风的缺血/再灌注(IR)过程通常导致明显的细胞死亡和永久性神经元损伤。迫切需要安全有效的治疗措施,以减轻IR伤害造成的损害。天然的多效性肽phoenixin 14(PNX-14)最近被发现可以作为IR损伤的潜在治疗方法。在本研究中,我们研究了PNX-14对涉及缺血性损伤的几个关键过程的影响,例如促炎性细胞因子表达,氧化应激以及通过Toll样受体4(TLR4)途径介导的相关级联反应,使用暴露于氧-葡萄糖剥夺和复氧(OGD / R)的BV2小胶质细胞。我们的结果证明PNX-14具有调节包括肿瘤坏死因子-α(TNF-α)在内的促炎细胞因子表达水平的急性能力,白介素1β(IL-1β)和白介素6(IL-6)。PNX-14还通过减少活性氧(ROS)的产生和增加抗氧化剂谷胱甘肽(GSH)的水平来防止氧化应激。重要的是,PNX-14通过抑制TLR4的激活并阻止核易位,抑制了高迁移率族1盒(HMGB1)/ TLR4 /骨髓分化主要反应88(MyD88)/核因子-κB(NF-κB)信号传导途径。 p65蛋白。我们进一步证实了PNX-14在MCAO大鼠模型中的脑保护作用,这导致梗死体积减少和小胶质细胞激活减少。总之,这项研究的结果暗示了PNX-14可能对IR损伤的各个方面起保护作用 PNX-14还通过减少活性氧(ROS)的产生和增加抗氧化剂谷胱甘肽(GSH)的水平来防止氧化应激。重要的是,PNX-14通过抑制TLR4的激活并阻止核易位,抑制了高迁移率族1盒(HMGB1)/ TLR4 /骨髓分化主要反应88(MyD88)/核因子-κB(NF-κB)信号传导途径。 p65蛋白。我们进一步证实了PNX-14在MCAO大鼠模型中的脑保护作用,这导致梗死体积减少和小胶质细胞激活减少。总之,这项研究的结果暗示了PNX-14可能对IR损伤的各个方面起保护作用 PNX-14还通过减少活性氧(ROS)的产生和增加抗氧化剂谷胱甘肽(GSH)的水平来防止氧化应激。重要的是,PNX-14通过抑制TLR4的激活并阻止核易位,抑制了高迁移率族1盒(HMGB1)/ TLR4 /骨髓分化主要反应88(MyD88)/核因子-κB(NF-κB)信号传导途径。 p65蛋白。我们进一步证实了PNX-14在MCAO大鼠模型中的脑保护作用,这导致梗死体积减少和小胶质细胞激活减少。总之,这项研究的结果暗示了PNX-14可能对IR损伤的各个方面起保护作用 PNX-14通过抑制TLR4的激活并阻止p65的核易位而抑制了高迁移率族1号框(HMGB1)/ TLR4 /髓样分化主要反应88(MyD88)/核因子-κB(NF-κB)信号通路。蛋白。我们进一步证实了PNX-14在MCAO大鼠模型中的脑保护作用,这导致梗死体积减少和小胶质细胞激活减少。总之,这项研究的结果暗示了PNX-14可能对IR损伤的各个方面起保护作用 PNX-14通过抑制TLR4的激活并阻止p65的核易位而抑制了高迁移率族1号框(HMGB1)/ TLR4 /髓样分化主要反应88(MyD88)/核因子-κB(NF-κB)信号通路。蛋白。我们进一步证实了PNX-14在MCAO大鼠模型中的脑保护作用,这导致梗死体积减少和小胶质细胞激活减少。总之,这项研究的结果暗示了PNX-14可能对IR损伤的各个方面起保护作用 这导致梗塞体积减少和小胶质细胞活化减少。总之,这项研究的结果暗示了PNX-14可能对IR损伤的各个方面起保护作用 这导致梗塞体积减少和小胶质细胞活化减少。总之,这项研究的结果暗示了PNX-14可能对IR损伤的各个方面起保护作用体外

更新日期:2020-05-23
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