MAPKs Modulate RPE Responseto Oxidative Stress

Abstract

To investigate the role of mitogen- activatedprotein kinases (MAPK) in the response of the retinal pigment epithelium (RPE) to oxidative stress (OS), a well-characterized RPE cell line (ARPE-19) was exposed to an oxidant-generating system catalyzed by glucose oxidase and glucose (GO/G). ARPE-19 cells were characterized for morphological changes, mitochondrial membrane permeability (MMP), and cell survival following exposure to GO/G. The effects of GO/G on MAPK activity were determined by assaying for p38MAPK expression and activity in the presence or absence of SB203580, a specific p38MAPK inhibitors, or p38MAPK siRNA. ARPE-19 cells exposed to GO/G showed morphological changes, increased MMP, and cell death. Exposure to OS promoted increased phosphorylation of p38MAPK and hsp27, a downstream target of p38MAPK. SB203580, but not p38 MAPK siRNA, inhibited ARPE-19 cell death. In conclusion, activation of p38MAPK may promote downstream pathways responsible for the morphological changes observed in RPE cells during oxidative damaging, however, these pathways do not appear to be responsible for OS-induced RPE degeneration.