Cholesterol regulation of genes involved in sterol trafficking in human THP-1 macrophages.
Modulation of the expression of genes involved in the control of cholesterol homeostasis by sterols in macrophages is crucial to foam cell formation. To characterize this regulation in THP-1 macrophages, we examined the effect of sterol loading and unloading on the expression of a number of genes that participate in lipoprotein uptake and cholesterol efflux. Sterol loading by exposure to acetylated LDL for 24 h resulted in an increase in free and esterified cholesterol of 1.4 and 1.8-fold, respectively. Under these conditions, the mRNA levels for SR-A were reduced a 59%, while those of CYP27 were increased by 4.6-fold. However, the expression of other genes involved in cholesterol efflux (ABCA1, ABCG1 and CLA-1) was not modified, despite a high intracellular cholesterol accumulation specially in the form of esterified cholesterol. On the other hand, HDL exposure reduced intracellular cholesterol content to 70%, and caused an increase in the expression of CD36 (78%), SR-A (51%) and CLA-1 (136%). Conversely, the expression of ABCA1, ABCG1 and CYP27 was decreased by 49, 67 and 57%, respectively. These findings indicate that in THP-1 macrophages, the expression of genes for receptors involved in lipoprotein binding and uptake tends to decrease upon cholesterol loading and to increase by cholesterol depletion, while the opposite pattern is found regarding the mRNA levels for proteins involved in cholesterol efflux.
Llaverias
Gemma
G
Unitat de Farmacologia, Departament de Farmacologia i Química Terapéutica, Facultat de Farmàcia, Universitat de Barcelona, Spain.
Lacasa
Diana
D
Vázquez-Carrera
Manuel
M
Sánchez
Rosa M
RM
Laguna
Juan C
JC
Alegret
Marta
M
D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D018955:CD36 Antigens; D002478:Cells, Cultured; D053493:Cholestanetriol 26-Monooxygenase; D002784:Cholesterol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D013250:Steroid Hydroxylases / Q000378:metabolism
C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D015415:Biomarkers; D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D002784:Cholesterol; D013250:Steroid Hydroxylases; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase