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首页> 外文期刊>Cellular Signalling >Activation of TNFR1 and TLR4 following oxygen glucose deprivation promotes mitochondrial fission in C6 astroglial cells
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Activation of TNFR1 and TLR4 following oxygen glucose deprivation promotes mitochondrial fission in C6 astroglial cells

机译:氧血糖剥夺后TNFr1和TLR4的激活促进了C6星形痛细胞中的线粒体裂变

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Astrocytes have emerged as active players in the innate immune response triggered by various types of insults. Recent literature suggests that mitochondria are key participants in innate immunity. The present study investigates the role of ischemia-induced innate immune response on p65/PGC-1 alpha mediated mitochondrial dynamics in C6 astroglial cells. OGD conditions induced astroglial differentiation in C6 cells and increased the expression of hypoxia markers; HIF-1 alpha, HO-1 and Cox4i2. OGD conditions resulted in induction of innate immune response in terms of expression of TNFR1 and TLR4 along with increase in IL-6 and TNF-alpha levels. OGD conditions resulted in decreased expression of I-kappa B with a concomitant increase in phos-p65 levels. The expression of PGC-1 alpha, a key regulator of mitochondrial biogenesis, was also increased. Immunochemical staining suggested that phos-p65 and PGC-1 alpha was co-localized. Studies on mitochondrial fusion (Mfn-1) and fission (DRP1) markers revealed shift toward fission. In addition, mitochondrial membrane potential decreased with increased DNA degradation and apoptosis confirming mitochondrial fission under OGD conditions. However, inhibition of phos-p65 by MG132 reduced the co-localization of phos-p65/ PGC-1 alpha and significantly increased the Mfn-1 expression. The findings demonstrate the involvement of TNFR1 and TLR4 mediated immune response followed by interaction between phos-p65 and PGC-1 alpha in promoting fission in C6 cells under hypoxic condition.
机译:星形胶质细胞在由各种类型的侮辱引发的先天免疫反应中被出现为活跃球员。最近的文献表明,线粒体是先天免疫的关键参与者。本研究研究了缺血诱导的先天免疫反应对C6时痛细胞中P65 / PGC-1α介导的线粒体动力学的作用。 OGD条件诱导C6细胞中的晕厥分化并增加缺氧标志物的表达; HIF-1α,HO-1和COX4I2。 OGD条件导致在TNFR1和TLR4的表达中诱导先天免疫应答,随着IL-6和TNF-α水平的增加。 OGD条件导致I-Kappa B表达降低,PHOS-P65水平的伴随增加。 PGC-1α的表达,线粒体生物发生的关键调节剂也增加了。免疫化学染色表明,PHOS-P65和PGC-1α是共定位的。线粒体融合(MFN-1)和裂变(DRP1)标记的研究显示出裂变的转变。此外,线粒体膜电位随着OGD条件下的DNA降解和细胞凋亡率增加而降低。然而,Mg132对PHOS-P65的抑制降低了PHOS-P65 / PGC-1α的共定位,并且显着增加了MFN-1表达。该研究结果证明了TNFR1和TLR4介导的免疫应答随后通过PHOS-P65和PGC-1α之间的相互作用在缺氧条件下促进C6细胞裂变中的促进。

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