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

Free Radic Biol Med. 1995 Sep;19(3):259-69. doi: 10.1016/0891-5849(95)00019-t.

Abstract

gamma-Tocopherol, commonly found in seed oils, is the major tocopherol in the U.S. diet, is superior to alpha-tocopherol in preventing neoplastic transformation, and demonstrates unique reactivity toward NO2. This article describes the products of reaction between gamma-tocopherol and low concentrations of gaseous nitrogen dioxide (NO2), as well as their endogenous formation in NO-producing RINm5F cells. gamma-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-trimethyltridecyl) 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 gamma-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 gamma-tocopherol. Tautomerization and further oxidation of the latter intermediate by NO2 yields tocored as the main product observed. The reaction of gamma-tocopherol with NO2 to form NO occurs independently of light, whereas alpha-tocopherol requires light to generate NO from NO2. gamma-Tocopherol and aminoguanidine, an NO synthase inhibitor, were superior to alpha-tocopherol in preventing RINm5F cell toxicity induced by Interleukin-1 beta (IL-1 beta). Both tocored and tocoyellow were observed to form in RINm5F cells loaded with gamma-tocopherol and producing NO constitutively, although a consistent increase in these products as a result of induced NO synthesis was not observed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biotransformation
  • Cell Line
  • Chromatography, High Pressure Liquid
  • Insulinoma / metabolism*
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Molecular Structure
  • Nitric Oxide / chemistry*
  • Nitric Oxide / metabolism*
  • Oxidation-Reduction
  • Pancreatic Neoplasms / metabolism*
  • Rats
  • Time Factors
  • Tumor Cells, Cultured
  • Vitamin E / chemistry*
  • Vitamin E / metabolism*

Substances

  • Vitamin E
  • Nitric Oxide