Stimulation of hepatic squalene and triglyceride synthesis by dimethylsulfoxide, in vitro

Abstract

The incorporation of [14C]mevalonate and [14C]acetate into squalene by rat liver slices was increased over 7-fold by the presence of 5% dimethylsulfoxide (DMSO) in the incubation medium. The stimulation of squalene synthesis was dose-related over the concentration range of 1-5% DMSO and did not affect the incorporation of [14C]mevalonate into the C27-sterol fraction (cholesterol) but did increase (about 50%) incorporation into C30-sterol (lanosterol) at a level of 5% DMSO. The stimulation of squalene synthesis was observed under both anaerobic (N2 atmosphere) and aerobic (ambient air or 95% O2/5% CO2) conditions and may represent a direct effect of DMSO on squalene synthetase. At a level of 5%, DMSO also stimulated 7-fold the incorporation of [14C]acetate into triglycerides by liver slices; this occurred without changes in incorporation into the phospholipid or free fatty acid fractions. The disproportionate increase in lipid labeling from [14C]acetate suggests that the effects of DMSO are not simply a matter of increasing [14C]acetate entry into the tissue.