One-electron reduction of chromium(VI) by alpha-lipoic acid and related hydroxyl radical generation, dG hydroxylation and nuclear transcription factor-kB activation.
Chen-F; Ye-J; Zhang-X; Rojanasakul-Y; Shi-X
Arch Biochem Biophys 1997 Feb; 338(2):165-172
Reaction of chromium(VI) with a-lipoic acid (reduced form, also called 1,2-dithiolane-3-pentanoic acid) generated Cr(V) and hydroxyl radical (.OH) as measured by electron spin resonance and ESR spin trapping. 5,5-Dimethyl-1-pyrroline was used as a spin trapping agent. Catalase inhibited the .OH generation and enhanced the Cr(V) formation. Superoxide dismutase had an opposite effect. H2O2enhanced the .OH generation and decreased the Cr(V) formation in a dose-dependent manner. Metal chelators, EDTA, diethylenetriaminepentaacetic acid, deferoxamine, and 1,10-phenanthroline inhibited .OH radical generation in the order of EDTA > 1,10-phenanthroline > DTPA > deferoxamine. Oxygen consumption measurements indicated that molecular oxygen was used to generate .OH radical in the mixture of Cr(VI) and a-lipoic acid. H2O2and superoxide radical (O2-) were involved as reactive intermediates. The .OH radical was generated via Cr(V)-mediated Fenton-like reaction (Cr(V) + H2O2--> Cr(VI) + OH-+.OH). HPLC measurements show that the .OH radical generated by this reaction is capable of generating 8-hydroxyl-2'-deoxyguanosine from 2-deoxyguanosine. Incubation of Cr(VI) with cultured Jurkat cells resulted in an activation of DNA binding activity of the nuclear factor (NF)-kB. Addition of a-lipoic acid enhanced the NF-kB activation, while the .OH radical scavenger, sodium formate, inhibited it, showing that a-lipoic acid enhanced Cr(VI)-induced NF-kB activation via free radical reactions. The results indicate that while a-lipoic acid is considered to be an antioxidant, it may be a cellular one-electron Cr(VI) reductant and could be involved in the mechanism of Cr(VI)-induced carcinogenesis.
Chromium-compounds; Carcinogens; Hydroxylation-reactions; Heavy-metals; Metal-compounds; Metallic-compounds; Respiratory-system-disorders; Pulmonary-system-disorders; Cell-function; Cellular-uptake; Oxidative-processes; Oxidation-reduction-reactions; Antioxidants
Xianglin Shi, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, 26505
18540-29-9; 70-18-8; 50-81-7
Archives of Biochemistry and Biophysics