title: Protective roles of ascorbic acid in oxidative stress induced by depletion of superoxide dismutase in vertebrate cells.
abstract: Superoxide dismutases (SODs) are antioxidant proteins that convert superoxide to hydrogen peroxide. In vertebrate cells, SOD1 is mainly present in the cytoplasm, with small levels also found in the nucleus and mitochondrial intermembrane space, and SOD2 is present in the mitochondrial matrix. Previously, the authors conditionally disrupted the SOD1 or SOD2 gene in DT40 cells and found that depletion of SOD1 caused lethality, while depletion of SOD2 led to growth retardation. The observations from previous work showed that the lethality observed in SOD1-depleted cells was completely rescued by ascorbic acid. Ascorbic acid is a water-soluble antioxidant present in biological fluids; however, the exact target for its antioxidant effects is not known. In this study, the authors demonstrated that ascorbic acid offset growth defects observed in SOD2-depleted cells and also lowered mitochondrial superoxide to physiological levels in both SOD1- or SOD2-depleted cells. Moreover, depletion of SOD1 or SOD2 resulted in the accumulation of intracellular oxidative stress, and this increased oxidative stress was reduced by ascorbic acid. Taken together, this study suggests that ascorbic acid can be applied as a nontoxic antioxidant that mimics the functions of cytoplasmic and mitochondrial SODs.
authors.affiliation: Laboratory of Radiation Biology, Division of Radiation Life Science, Research Reactor Institute, Kyoto University, Osaka, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tamari
authors.forename: Hisakatsu
authors.initials: H
authors.lastname: Nawata
authors.forename: Eri
authors.initials: E
authors.lastname: Inoue
authors.forename: Akari
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Hanako
authors.initials: H
authors.lastname: Yoshii
authors.forename: Genro
authors.initials: G
authors.lastname: Kashino
authors.forename: Masayuki
authors.initials: M
authors.lastname: Seki
authors.forename: Takemi
authors.initials: T
authors.lastname: Enomoto
authors.forename: Masami
authors.initials: M
authors.lastname: Watanabe
authors.forename: Keizo
authors.initials: K
authors.lastname: Tano
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D002645:Chickens; D055786:Gene Knockout Techniques; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014714:Vertebrates; D000099156:Superoxide Dismutase 2
chemical_list: D000975:Antioxidants; D001205:Ascorbic Acid; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C000606290:SOD1 protein, human