Role of p38 Mitogen-Activated Protein Kinase in Axotomy-Induced Apoptosis of Rat Retinal Ganglion Cells

摘要: p38 is a member of the mitogen-activated protein (MAP) kinase superfamily and mediates intracellular signal transduction. Recent studies suggest that involved in apoptotic signaling several cell types, including neurons. In mammalian retina, ∼50% retinal ganglion cells (RGCs) die by apoptosis during development. Additionally, transection optic nerve close to eye bulb causes death RGCs adulthood. We investigated role axotomy-induced RGCs. One day after axotomy, activated (phosphorylated) was visualized immunocytochemistry nuclei RGCs, but not control retinas. Phosphorylated first detected on immunoblots 12 hr reached maximum at 1 d, then decreased. To investigate possible roles RGC death, MAP inhibitor, SB203580, administered intravitreally time axotomy repeated 5 10 d. Assayed 14 d SB203580 increased number surviving dose-dependent manner (the minimum effective concentration 1.6 μm). Furthermore, MK801, selective inhibitor NMDA receptors, only showed protective effects against also attenuated activation manner. Our findings imply pathway mediated glutamate neurotoxicity through receptors damage nerve. inhibitors could be potentially useful for treatment trauma neurodegenerative diseases affect such as glaucoma.