title: Physiological copper exposure in Jurkat cells induces changes in the expression of genes encoding cholesterol biosynthesis proteins.
abstract: Copper is an essential micronutrient that functions as an enzymatic cofactor in a wide range of cellular processes. Although adequate Cu levels are essential for normal metabolism, excess Cu can be toxic to cells. Cellular responses to copper deficiency and overload involve changes in the expression of genes directly and indirectly involved in copper metabolism. However little is known on the effect of physiological copper concentration on gene expression changes. In the current study we aimed to establish whether the expression of genes encoding enzymes related to cholesterol (hmgcs1, hmgcr, fdft) and fatty acid biosynthesis and LDL receptor can be induced by an iso-physiological copper concentration. The iso-physiological copper concentration was determined as the bioavailable plasmatic copper in a healthy adult population. In doing so, two blood cell lines (Jurkat and THP-1) were exposed for 6 or 24 h to iso- or supraphysiological copper concentrations. Our results indicated that in cells exposed to an iso-physiological copper concentration the early induction of genes involved in lipid metabolism was not mediated by copper itself but by the modification of the cellular redox status. Thus our results contributed to understand the involvement of copper in the regulation of cholesterol metabolism under physiological conditions.
authors.affiliation: Laboratorio de Bioinformática y Expresión Génica, INTA, Universidad de Chile, El Líbano 5524, Macul, Santiago, Chile.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gutiérrez-García
authors.forename: Talía
authors.initials: T
authors.lastname: del Pozo
authors.forename: Miriam
authors.initials: M
authors.lastname: Suazo
authors.forename: Verónica
authors.initials: V
authors.lastname: Cambiazo
authors.forename: Mauricio
authors.initials: M
authors.lastname: González
mesh_terms: D002784:Cholesterol / Q000096:biosynthesis* / Q000235:genetics; D003300:Copper / Q000494:pharmacology*; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000235:genetics / Q000378:metabolism; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006639:Histidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells; D050356:Lipid Metabolism / Q000187:drug effects; D009942:Organometallic Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism
chemical_list: C573412:LDLR protein, human; D009942:Organometallic Compounds; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011973:Receptors, LDL; D006639:Histidine; D003300:Copper; C098468:copper histidine; D002784:Cholesterol; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; D006904:Hydroxymethylglutaryl-CoA Synthase; D013186:Farnesyl-Diphosphate Farnesyltransferase