Activation of TNFR1 and TLR4 following oxygen glucose deprivation promotes mitochondrial fission in C6 astroglial cells.

Activation of TNFR1 and TLR4 following oxygen glucose deprivation promotes mitochondrial fission in C6 astroglial cells. Cell Signal. 2020 Jul 18;:109714 Authors: Halder A, Yadav K, Aggarwal A, Singhal N, Sandhir R Abstract 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-1α mediated mitochondrial dynamics in C6 astroglial cells. OGD conditions induced astroglial differentiation in C6 cells and increased the expression of hypoxia markers; HIF-1α, HO-1 and Cox4i2. OGD conditions resulted in induction of innate immune response in terms of expression of TNFR1 and TLR4 along with IL-6 and TNF-α levels. OGD conditions resulted in decreased expression of I-κB with a concomitant increase in phos-p65 levels. The expression of PGC-1α, a key regulator of mitochondrial biogenesis, was also increased. Immunological studies suggested that phos-p65 and PGC-1α co-localize. Studies on mitochondrial fusion (Mfn-1) and fission (DRP1) markers revealed shift toward fission. In addition, mitochondrial membrane potential decreased with increased degradation of DNA and apoptosis confirming mitochondrial fission under OGD conditions. However, inhibition of p65 activation by MG132 reduced the co-localization of pho...
Source: Cellular Signalling - Category: Cytology Authors: Tags: Cell Signal Source Type: research