7-Ketocholesteryl-9-carboxynonanoate enhances the expression of ATP-binding cassette transporter A1 via CD36

Background: CD36 signal transductions have been reported by a variety of lipid moiety of oxidized low-density lipoprotein (oxLDL), however, CD36 signal induced by 7-ketocholesteryl-9-carboxynonanoate (oxLig-1), a lipid moiety of oxLDL has not been elucidated. Methods and results: OxLig-1 leads to activation and recruitment of Src kinase Fyn, Lyn and caveolin-1 to CD36 in J774A.1 cells, but not in CD36 knockdown cells. The mitogen-activated protein (MAP) kinases c-Jun N-terminal kinase 2 (JNK2) and extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) are specifically phosphorylated in J774A.1 cells after treatment with oxLig-1 and inhibited by pretreatment of Src inhibitor, AG1879. The expression of ABCA1 is up-regulated by treatment with oxLig-1in J774A.1 cells, and the increased expression of ABCA1 is dramatically down-regulated by pretreatment with pharmacological inhibitors of ERK (PD98059) and JNK (SP600125). Conclusions: The specific CD36 signal induced by oxLig-1 initiated the activation of Fyn, Lyn, caveolin-1, JNK2 and ERK1/2, and resulted in the up-regulation of ABCA1.