Activation of TNFR1 and TLR4 following oxygen glucose deprivation promotes mitochondrial fission in C6 astroglial cells.
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 increase in 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. Immunochemical staining suggested that phos-p65 and PGC-1α 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...Continue Reading
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