Are side-chain oxidized oxysterols regulators also in vivo?

摘要: Oxsterols are oxygenated metabolites of cholesterol that short-lived intermediates or end products in excretion pathways. They present very low concentrations mammalian systems, always accompanied by a high excess cholesterol. According to current concepts, side-chain oxidized oxysterols may be mediators many cholesterol-induced regulatory effects. When added cultured cells vitro, limit intracellular levels at least three different mechanisms: 1) binding Insig with subsequent block the sterol element-binding proteins (SREBP)-mediated mechanism for regulation sensitive genes; 2) increasing degradation hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, eventually involving enzyme; 3) activation LXR-mediated stimulation transporters and metabolism. Addition pure unesterified cell cultures is however highly unphysiological, vivo relevance such experiments questionable. Transgenic mouse models markedly reduced increased concentration some specific do not marked disturbances turnover homeostasis. Oxysterol-binding as LXR have been conclusively shown importance vivo, but their physiological ligands yet defined certainty. During last few years, new experimental data has accumulated supporting contention involved biological systems. The findings will critically reviewed here.