Modulation of Rho-Rock signaling pathway protects oligodendrocytes against cytokine toxicity via PPAR-α-dependent mechanism.

ABSTRACT: We earlier documented that lovastatin (LOV)-mediated inhibition of small Rho GTPases activity protects vulnerable oligodendrocytes (OLs) in mixed glial cell cultures stimulated with Th1 cytokines and in a murine model of multiple sclerosis (MS). However, the precise mechanism of OL protection remains unclear. We here employed genetic and biochemical approaches to elucidate the underlying mechanism that protects LOV treated OLs from Th1 (tumor necrosis factor-α) and Th17 (interleukin-17) cytokines toxicity in in vitro. Cytokines enhanced the reactive oxygen species (ROS) generation and mitochondrial membrane depolarization with corresponding lowering of glutathione (reduced) level in OLs and that were reverted by LOV. In addition, the expression of ROS detoxifying enzymes (catalase and supe

SUBMITTER: Paintlia AS 

PROVIDER: S-EPMC3919553 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature