Effect of methionine sulfoxide reductase B1 (SelR) gene silencing on peroxynitrite-induced F-actin disruption in human lens epithelial cells.

F-actin plays a crucial role in fundamental cellular processes, and is extremely susceptible to peroxynitrite attack due to the high abundance of tyrosine in the peptide. Methionine sulfoxide reductase (Msr) B1 is a selenium-dependent enzyme (selenoprotein R) that may act as a reactive oxygen species (ROS) scavenger. However, its function in coping with reactive nitrogen species (RNS)-mediated stress and the physiological significance remain unclear. Thus, the present study was conducted to elucidate the role and mechanism of MsrB1 in protecting human lens epithelial (hLE) cells against peroxynitrite-induced F-actin disruption. While exposure to high concentrations of peroxynitrite and gene silencing of MsrB1 by siRNA alone caused disassembly of F-actin via inactivation of extracellular signal-regulated kinase (ERK) in hLE cells, the latter substantially aggravated the disassembly of F-actin triggered by the former. This aggravation concurred with elevated nitration of F-actin and inactivation of ERK compared with that induced by the peroxynitrite treatment alone. In conclusion, MsrB1 protected hLE cells against the peroxynitrite-induced F-actin disruption, and the protection was mediated by inhibiting the resultant nitration of F-actin and inactivation of ERKs.