title: Glutathione in Cellular Redox Homeostasis: Association with the Excitatory Amino Acid Carrier 1 (EAAC1).
abstract: Reactive oxygen species (ROS) are by-products of the cellular metabolism of oxygen consumption, produced mainly in the mitochondria. ROS are known to be highly reactive ions or free radicals containing oxygen that impair redox homeostasis and cellular functions, leading to cell death. Under physiological conditions, a variety of antioxidant systems scavenge ROS to maintain the intracellular redox homeostasis and normal cellular functions. This review focuses on the antioxidant system's roles in maintaining redox homeostasis. Especially, glutathione (GSH) is the most important thiol-containing molecule, as it functions as a redox buffer, antioxidant, and enzyme cofactor against oxidative stress. In the brain, dysfunction of GSH synthesis leading to GSH depletion exacerbates oxidative stress, which is linked to a pathogenesis of aging-related neurodegenerative diseases. Excitatory amino acid carrier 1 (EAAC1) plays a pivotal role in neuronal GSH synthesis. The regulatory mechanism of EAAC1 is also discussed.
authors.forename: Koji
authors.initials: K
authors.lastname: Aoyama
authors.forename: Toshio
authors.initials: T
authors.lastname: Nakaki
mesh_terms: D000975:Antioxidants / Q000737:chemistry; D001921:Brain / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism*; D005978:Glutathione / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000473:pathology*; D018696:Neuroprotective Agents; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D050580:Excitatory Amino Acid Transporter 3; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C493400:SLC1A1 protein, human; D005978:Glutathione
keywords: EAAC1; glutathione; neurodegeneration; oxidative stress