Raf kinase inhibitor protein protects microglial cells against 1-methyl-4-phenylpyridinium-induced neuroinflammation in vitro

Abstract

The Raf kinase inhibitor protein (RKIP), belonging to a member of the phosphatidylethanolamine-binding protein (PEBP) family, is involved in regulating neural development. However, the role of RKIP in microglial cells stimulated with 1-methyl-4-phenylpyridinium (MPP+) has not been determined. Thus, in the present study, we investigated the role of RKIP and its underlying mechanism in Parkinson's disease (PD). Our results showed that the expression of RKIP was significantly reduced in BV-2 cells treated with MPP+. Overexpression of RKIP markedly rescued cell viability and inhibited cell apoptosis in BV-2 cells exposed to MPP+. In addition, overexpression of RKIP inhibited MPP+-induced the production of pro-inflammatory molecules in BV-2 cells. Similar results were observed in primary microglial cells isolated from neonatal mice. Exploration of the underlying mechanisms of its action indicated that overexpression of RKIP prevented the activation of NF-κB and MEK/ERK pathways in MPP+-stimulated BV-2 cells. Taken together, these findings indicated that RKIP suppresses apoptosis and inflammation in MPP+-treated microglial cells through the inactivation of NF-κB and MEK/ERK signaling pathways. Thus, RKIP may be a promising target molecular involving in the pathogenesis of PD.