title: Elevated Cytoplasmic Free Zinc and Increased Reactive Oxygen Species Generation in the Context of Brain Injury.
abstract: Intracellular zinc release and the generation of reactive oxygen species (ROS) have been reported to be common ingredients in numerous toxic signaling mechanisms in neurons. A key source for intracellular zinc release is its liberation from metallothionein-III (MT-III). MT-III binds and regulates intracellular zinc levels under physiological conditions, but the zinc-binding thiols readily react with certain ROS and reactive nitrogen species (RNS) to result in intracellular zinc liberation. Liberated zinc induces ROS and RNS generation by multiple mechanisms, including the induction of mitochondrial ROS production, and also promotes ROS formation outside the mitochondria by interaction with the enzymes NADPH oxidase and 12-lipoxygenase. Of particular relevance to neuronal injury in the context of ischemia and prolonged seizures, the positive feedback cycle between ROS/RNS generation and increasing zinc liberation will be examined.
authors.affiliation: Department of Biomedical Sciences, Ohio University Heritage College of Osteopathic Medicine, Irvine Hall, Athens, OH, 45701, USA. storkc@ohio.edu.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Stork
authors.affiliation: Department of Biomedical Sciences, Ohio University Heritage College of Osteopathic Medicine, Irvine Hall, Athens, OH, 45701, USA. liy1@ohio.edu.
authors.forename: Yang V
authors.initials: YV
authors.lastname: Li
mesh_terms: D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D001092:Arachidonate 12-Lipoxygenase; D019255:NADPH Oxidases; D015032:Zinc; D002118:Calcium
keywords: Calcium; Oxidative stress; RNS; ROS; Zinc