Cigarette Smoke-Related Hydroquinone Induces Filamentous Actin Reorganization and Heat Shock Protein 27 Phosphorylation through p38 and Extracellular Signal-Regulated Kinase 1/2 in Retinal Pigment Epithelium: Implications for Age-Related Macular Degeneration

摘要: Retinal pigment epithelium (RPE)-derived membranous debris named blebs, may accumulate and contribute to sub-RPE deposit formation, which is the earliest sign of age-related macular degeneration (AMD). Oxidative injury RPE might play a significant role in AMD. However, underlying mechanisms are unknown. We previously reported that hydroquinone (HQ), major pro-oxidant cigarette smoke, foodstuff, atmospheric pollutants, induces actin rearrangement membrane blebbing cells as well deposits mice. Here, we show for first time phosphorylated Heat shock protein 27 (Hsp27), key regulator filaments dynamics, up-regulated from patients with Also, HQ-induced nonlethal oxidative led Hsp27mRNA up-regulation, dimer Hsp27 phosphorylation ARPE-19 cells. Furthermore, found cross talk between p38 extracellular signal-regulated kinase (ERK) mediates aggregate revealing ERK novel upstream mediator phosphorylation. Finally, demonstrated Hsp25, p38, increased aging C57BL/6 mice chronically exposed HQ, whereas Hsp25 expression decreased. Our data suggest be AMD RPE, provide helpful insights into early cellular events associated reorganization bleb formation involved relevant pathogenesis