Effect of cyclosporine and sirolimus on fatty acid desaturase activities in cultured HEPG2 cells

LAUSADA NATALIA; GóMEZ DUMM I.N.TACCONI DE; RAIMONDI J.C.; TACCONI DE ALANIZ MARíA J.

TRANSPLANTATION PROCEEDINGS

Elsevier

Lugar: New York; Año: 2008

0041-1345

Microsomal enzymes called fatty acid (FA) desaturases catalysed the biosynthesis of monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) adding double bonds to acyl-CoA. N-6 FA family tends to inflammation  whereas n-3 FA is involved in the prevention of vascular events which appear after successful kidney transplantation. The aim of the present work was to evaluate the influence of cyclosporine (CsA) and sirolimus (SRL) on desaturase activities. Five groups of HepG2 cells in culture were treated with either CsA (1µg/µL and 2µg/µL) or SRL (10ng/mL and 20ng/mL) for 3 days, including a Control group without immunosuppressive treatment. After 72h the cells were harvested, FA were analysed by gas-liquid-chromatography. The procedure was repeated and radiolabeled FA: palmitic-[1-14C] or linoleic-[1-14C] or eicosatrienoic-[1-14C] acid were added on the third day of the immunosuppressive treatment. The distribution of radioactivity among methyl FA was analysed by gas-liquid-radiochromatography. The distribution of radioactive metabolic products after the incubation of these cells with [1-14C]palmitic acid revealed a decrease in Ä9 desaturase activity in the presence of each immunosuppressive drugs (CsA: 0.61±0.01; SRL: 0.59±0.04 vs. Control 0.79±0.05; p<0.01). A significant increase in Ä6 and Ä5 desaturase activities under the influence of each immunosuppressive drug was observed: radiolabeled linoleic acid (CsA: 0.93±0.04; SRL: 1.02±0.03 vs. control 0.60±0.03; p<0.01) and eicosatrienoic acid (CsA: 1.12±0.02; SRL: 1.07±0.01 vs. control 0.75±0.01; p<0.01). In conclusion, CsA and SRL modulate the biosynthesis of  PUFAs, decreasing Ä9 desaturase and increasing Ä6 and Ä5 desaturase activities.