QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Turley, C. P. Articles by Brewster, M. A. Search for Related Content PubMed PubMed Citation Articles by Turley, C. P. Articles by Brewster, M. A.

-Tocopherol Protects Against a Reduction in Adenosylcobalamin in Oxidatively Stressed Human Cells¹

Departments of Pathology and Biochemistry, University of Arkansas for Medical Sciences, Little Rock, AR 72204

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 -tocopherol. In both cell types, labeling of AdoCbl was lower in the presence of linoleate unless -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 -tocopherol. We conclude that lipoperoxidation reduces mitochondrial AdoCbl formation and that -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.

KEY WORDS: • vitamin B-12 • tocopherol • human cell culture • lipoperoxides • adenosylcobalamin

¹ A summary report of this work has been published in abstract form [Turley, C. P. & Brewster, M. A. (1986) Effects of tocopherol on cobalamin metabolism in cultured human cells. Ann. Clin. Lab. Sci. 16: 318 (abs.)].

² To whom correspondence should be addressed.

Manuscript received 9 September 1992. Revision accepted 19 February 1993.