Alpha-tocopherol protects against a reduction in adenosylcobalamin in oxidatively stressed human cells.
Excretion of methylmalonic acid by vitamin E-deficient patients and decreased labeling of adenosylcobalamin (AdoCbl) from cyanocobalamin in vitamin E-deficient rats suggest an interaction of vitamins E and B-12. We studied this interaction in two human cell culture systems: foreskin fibroblasts and a hepatoma cell line (HepG2). We measured radiolabeling of AdoCbl and methylcobalamin from [57Co]hydroxycobalamin for 6 d in the presence and absence of linoleate (an oxidative stressor) and alpha-tocopherol. In both cell types, labeling of AdoCbl was lower in the presence of linoleate unless alpha-tocopherol was present. The decrease was accentuated by peroxidized linoleic acid; AdoCbl synthetic rate was inversely associated with thiobarbituric acid-reactive compound concentration. Subcellular partitioning of labeled cobalamin revealed less in mitochondria in the linoleate-stressed cells that were not treated with alpha-tocopherol. We conclude that lipoperoxidation reduces mitochondrial AdoCbl formation and that alpha-tocopherol exerts a protective effect in oxidatively stressed cells. We suggest that this subcellular deficiency in AdoCbl may be one mechanism by which vitamin E deficiency leads to neurologic injury. The mechanism seems primarily to involve an alteration in intracellular cobalamin distribution with perhaps a minor effect upon enzymes of AdoCbl synthesis.
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock 72204.
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Turley
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Brewster
D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002478:Cells, Cultured; D003038:Cobamides / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008113:Liver Neoplasms / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
D003038:Cobamides; D008041:Linoleic Acids; D014810:Vitamin E; D019787:Linoleic Acid; C000913:cobamamide