Effects of PACAP on Intracellular Signaling Pathways in Human Retinal Pigment Epithelial Cells Exposed to Oxidative Stress

摘要: The integrity of retinal pigment epithelial cells is critical for photoreceptor survival and vision. Pituitary adenylate cyclase activating polypeptide (PACAP) exerts retinoprotective effects against several types injuries in vivo, including optic nerve transection, ischemia, excitotoxic injuries, UVA-induced lesion, diabetic retinopathy. In a recent study, we have proven that PACAP also protective oxidative stress-induced injury human (ARPE-19 cells). aim the present study was to investigate possible mechanisms this protection. ARPE were exposed 24-h hydrogen peroxide treatment. Expressions kinases apoptotic markers studied by complex array kits Western blot. Oxidative stress induced activation markers, Bad, Bax, HIF-1α, heat shock proteins, TNF-related apoptosis-inducing ligand, Fas-associated protein with death domain, while treatment decreased them. changes expression MAP showed activated ERK1/2 downstream CREB, pro-apoptotic p38MAPK c-Jun N-terminal kinase, an effect opposite observed only stress. Furthermore, increased Akt pathway. addition, on other signaling molecules counteracted (Chk2, Yes, Lyn, paxillin, p53, PLC, STAT4, RSK). These play role cell death, cycle, inflammation, adhesion, differentiation proliferation. summary, PACAP, acting at levels, influences balance between pro- anti-apoptotic factors favor anti-apoptosis, thereby providing protection cells.