Δ5 desaturase mRNA levels are increased by simvastatin via SREBP-1 at early stages, not via PPARα, in THP-1 cells

摘要: In addition to inhibiting cholesterol biosynthesis, statins increase the conversion of linoleic acid its derivatives, in particular arachidonic acid, both vivo and vitro. Desaturases are rate-limiting enzymes this metabolic process markedly enhance delta5 desaturase activity. To evaluate gene expression transcription factors involved, THP-1 cells (a monocytic cell line) were incubated with 5 microM simvastatin for different time periods. The activity enzyme, evaluated as product/precursor ratio pathway (starting from [1-(14)C] acid), increased treated respect controls after 24 h, whereas, mRNA levels 12 h incubation simvastatin. Fatty genes regulated by sterol regulatory element binding proteins (SREBPs) peroxisome proliferators activated receptors (PPARs). Both PPARalpha (WY 14643 fenofibrate) PPARgamma (ciglitazone) agonists did not affect at any considered (8-48 h), but they levels, 48 h; only fenofibrate showed a synergistic effect time, concomitantly beta-oxidation. Simvastatin alone SREBP-1 controls, starting 8 incubation, whereas beta-oxidation mediated process) affected incubation. These results taken together suggest that is involved early regulation simvastatin, cells.