tailieunhanh - Báo cáo khoa học: Oxidative neuronal injury The dark side of ERK1/2

The extracellular signal regulated protein kinases (ERK1/2) are essential for normal development and functional plasti-city of the central nervous system. However, a growing number of recent studies in models of cerebral ischemia, brain trauma and neurodegenerative diseases implicate a detrimental role for ERK1/2 signaling during oxidative neuronal injury. Neurons undergoing oxidative stress-rela-ted injuries typically display a biphasic or sustained pattern of ERK1/2 activation. A variety of potential targets of reactive oxygen species and reactive nitrogen species could contribute to ERK1/2 activation | Eur. J. Biochem. 271 2060-2066 2004 FEBS 2004 doi MINIREVIEW Oxidative neuronal injury The dark side of ERK1 2 Charleen T. Chu1 4 David J. Levinthal3 4 Scott M. Kulich1 Elisabeth M. Chalovich1 and Donald B. DeFranco2 3 4 1 Department of Pathology 2Department of Pharmacology 3Department of Neuroscience and 4Center for Neuroscience University of Pittsburgh School of Medicine Pittsburgh PA USA The extracellular signal regulated protein kinases ERK1 2 are essential for normal development and functional plasticity of the central nervous system. However a growing number of recent studies in models of cerebral ischemia brain trauma and neurodegenerative diseases implicate a detrimental role for ERK1 2 signaling during oxidative neuronal injury. Neurons undergoing oxidative stress-related injuries typically display a biphasic or sustained pattern of ERK1 2 activation. A variety of potential targets of reactive oxygen species and reactive nitrogen species could contribute to ERK1 2 activation. These include cell surface receptors G proteins upstream kinases protein phosphatases and proteasome components each of which could be direct or indirect targets of reactive oxygen or nitrogen species thereby modulating the duration and magnitude of ERK1 2 activation. Neuronal oxidative stress also appears to influence the subcellular trafficking and or localization of activated ERK1 2. Differences in compartmentalization of phosphorylated ERK1 2 have been observed in diseased or injured human neurons and in their respective animal and cell culture model systems. We propose that differential accessibility of ERK1 2 to downstream targets which is dictated by the persistent activation of ERK1 2 within distinct subcellular compartments underlies the neurotoxic responses that are driven by this kinase. Keywords Alzheimer s disease cerebral ischemia mitogen activated protein kinases neurodegeneration neuronal cell death oxidative stress Parkinson s disease