title: Inhibition of ERK1/2 improves lipid balance in rat macrophages via ABCA1/G1 and CD36.
abstract: ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1), and macrophage scavenger receptor, cluster of differentiation (CD)36, function as key mediators of cholesterol efflux and influx from macrophages. In addition, they are associated with foam cell formation and the development of atherosclerosis (AS). The aim of the present study was to investigate the effects of extracellular signal-regulated kinases 1/2 (ERK1/2) inhibition on lipid balance in oxidized-low-density lipoprotein (Ox-LDL)-stimulated rat macrophages, and to examine the role of ERK1/2 inhibitors in AS. Rat peritoneal macrophages were treated with Ox-LDL alone or in combination with an ERK1/2 inhibitor, U0126, and untreated cells served as controls. Ox-LDL-induced lipid accumulation was detected by DiI fluorescence and oil red O staining. In addition, the mRNA and protein expression levels of ABCA1, ABCG1 and CD36 were determined using polymerase chain reaction and western blotting, respectively. Treatment with Ox-LDL significantly increased lipid accumulation and upregulated the mRNA and protein expression levels of ABCA1, ABCG1 and CD36 in macrophages. The addition of U0126 resulted in a marked reduction of lipid deposition, upregulation of ABCA1/G1 expression and suppression of CD36 expression in Ox-LDL-stimulated macrophages. The results of the present study indicated a novel association between ERK1/2 signaling and lipid metabolism, thus suggesting that inhibition of ERK1/2 may be considered a promising therapeutic strategy against AS.
authors.affiliation: Department of Neurology, Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350003, P.R. China.
authors.forename: Xie-Hua
authors.initials: XH
authors.lastname: Xue
authors.affiliation: Institute of Rehabilitation Medicine, Rehabilitation Technology Collaborative Innovation Center, College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350003, P.R. China.
authors.forename: Feng-Fei
authors.initials: FF
authors.lastname: Shi
authors.affiliation: Institute of Rehabilitation Medicine, Rehabilitation Technology Collaborative Innovation Center, College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350003, P.R. China.
authors.forename: Tong
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Neurology, Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350003, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Institute of Rehabilitation Medicine, Rehabilitation Technology Collaborative Innovation Center, College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350003, P.R. China.
authors.forename: Xiao-Mao
authors.initials: XM
authors.lastname: Zhou
authors.affiliation: Institute of Rehabilitation Medicine, Rehabilitation Technology Collaborative Innovation Center, College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350003, P.R. China.
authors.forename: Li-Dian
authors.initials: LD
authors.lastname: Chen
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000096:biosynthesis* / Q000235:genetics; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002070:Butadienes / Q000008:administration & dosage; D018955:CD36 Antigens / Q000096:biosynthesis* / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000008:administration & dosage; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009570:Nitriles / Q000008:administration & dosage; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D002070:Butadienes; D018955:CD36 Antigens; D002784:Cholesterol; D008077:Lipoproteins, LDL; D009570:Nitriles; D012333:RNA, Messenger; C577834:Abca1 protein, rat; C559724:Abcg1 protein, rat; C008132:Cd36 protein, rat; C113580:U 0126; C099252:oxidized low density lipoprotein