Products of γ-tocopherol reaction with NO2 and their formation in rat insulinoma (RINm5F) cells

Robert V. Cooney, Patricia J. Harwood, Adrian A. Franke, Kavitha Narala, Anna Karin Sundström, Per Olof Berggren, Lawrence J. Mordan

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Abstract

γ-Tocopherol, commonly found in seed oils, is the major tocopherol in the U.S. diet, is superior to α-tocopherol in preventing neoplastic transformation, and demonstrates unique reactivity toward NO2. This article describes the products of reaction between γ-tocopherol and low concentrations of gaseous nitrogen dioxide (NO2), as well as their endogenous formation in NO-producing RINm5F cells. γ-Tocopherol in hexane reacts with NO2 to yield two products identified as 2,7,8-trimethyl-2(4,8,12-trimethyltridecyl)-5,6-chromaquinone, "tocored," and 2,7,8 trimethyl-2(4,8,12-trimethyldecyl) 5-nitro, 6-chromanol, "tocoyellow." Physical data for these two compounds and reaction characteristics are described. The formation of tocored is consistent with a proposed mechanism of γ-tocopherol-mediated reduction of NO2 to NO involving initial reaction by NO2 at the C-5 position to form an intermediate nitrite ester tocopheryl radical, which then reacts internally to release NO and form 5,6 epoxy γ-tocopherol. Tautomerization and further oxidation of the latter intermediate by NO2 yields tocored as the main product observed. The reaction of γ-tocopherol with NO2 to form NO occurs independently of light, whereas a-tocopherol requires light to generate NO from NO2. γ-Tocopherol and aminoguanidine, an NO synthase inhibitor, were superior to α-tocopherol in preventing RINm5F cell toxicity induced by Interleukin-1β (IL-1β). Both tocored and tocoyellow were observed to form in RINm5F cells loaded with γ-tocopherol and producing NO constitutively, although a consistent increase in these products as a result of induced NO synthesis was not observed.

Original languageEnglish (US)
Pages (from-to)259-269
Number of pages11
JournalFree Radical Biology and Medicine
Volume19
Issue number3
DOIs
StatePublished - Sep 1995

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Keywords

  • Antioxidants
  • Epoxides
  • Free radicals
  • Nitration
  • Nitric oxide
  • Nitrogen Oxides
  • Tocopherol

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)
  • Clinical Biochemistry
  • Medicine(all)
  • Toxicology

Cite this

Cooney, R. V., Harwood, P. J., Franke, A. A., Narala, K., Sundström, A. K., Berggren, P. O., & Mordan, L. J. (1995). Products of γ-tocopherol reaction with NO2 and their formation in rat insulinoma (RINm5F) cells. Free Radical Biology and Medicine, 19(3), 259-269. https://doi.org/10.1016/0891-5849(95)00019-T