Cooperation of docosahexaenoic acid and vitamin E in the regulation of UDP-glucuronosyltransferase mRNA expression.

Docosahexaenoic acid (DHA) is a well known chemopreventive nutrient within diet formulations, but it may also exert toxic effects on cultured cells, while this is limited when also another relevant nutrient as vitamin E is present. This effect, beside the involvement of the two nutrients in oxidative processes, likely affects the expression of specific genes. To obtain information on combined activities of DHA and vitamin E on some gene products previously resulted to be in vivo regulated from dietary unsaturated fats, the effect of the two nutrients was evaluated in human cell line HepG2. Independently, DHA and vitamin E resulted to affect only slightly UDP-glucuronosyltransferase 1A1 (UGT1A1) mRNA expression. Nevertheless, their combination produced a considerable reduction of this mRNA. DHA also downregulated stearoyl-CoA desaturase (SCD) and sterol regulatory element binding protein (SREBP-1) expression, while vitamin E did not affect these products. However, their combination abolished the downregulation of SCD but did not affect that of SREBP-1. Therefore the effect of the two nutrients is related to specific gene regulation processes resulting in a cooperation which might be related to their physiological effects as dietary components.