title: Intracellular zinc release, 12-lipoxygenase activation and MAPK dependent neuronal and oligodendroglial death.
abstract: Zinc translocation from presynaptic nerve terminals to postsynaptic neurons has generally been considered the critical step leading to the accumulation of intracellular free zinc and subsequent neuronal injury. Recent evidence, however, strongly suggests that the liberation of zinc from intracellular stores upon oxidative and nitrative stimulation contributes significantly to the toxicity of this metal not only to neurons, but also to oligodendrocytes. The exact cell death signaling pathways triggered by zinc are beginning to be deciphered. In this review, we describe how the activation of 12-lipoxygenase and mitogen-activated protein kinase (MAPK) contribute to the toxicity of liberated zinc to neurons and oligodendrocytes.
authors.affiliation: Department of Anatomy, Physiology and Genetics and Program in Neuroscience, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA. yzhang@usuhs.mil
authors.forename: Yumin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Elias
authors.initials: E
authors.lastname: Aizenman
authors.forename: Donald B
authors.initials: DB
authors.lastname: DeFranco
authors.forename: Paul A
authors.initials: PA
authors.lastname: Rosenberg
mesh_terms: D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D016923:Cell Death; D004789:Enzyme Activation; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D009836:Oligodendroglia / Q000166:cytology / Q000201:enzymology*; D018384:Oxidative Stress; D051381:Rats; D015032:Zinc / Q000378:metabolism / Q000633:toxicity*
chemical_list: D008668:Metallothionein; D001092:Arachidonate 12-Lipoxygenase; D020928:Mitogen-Activated Protein Kinases; D015032:Zinc