出版社：American Society for Biochemistry and Molecular Biology
摘要：ABCA1 is a critical regulator of lipid efflux from cells, whichis highly regulated at the transcriptional and posttranslationallevels. However, cells from different species and differenttissues, and primary versus immortalized cells, show differentmodes of regulation. We have carried out a comparative analysisof basic signaling pathways of lipid efflux in mouse J774 cells,mouse peritoneal macrophages (MPMs), human THP-1 cells, andhuman monocyte-derived macrophages. Cyclic AMP (cAMP) was apotent stimulator of lipid efflux in mouse macrophages, butnot in human macrophages. Moreover, this cAMP-inducible componentof efflux from MPMs was inhibitable by H89 [a protein kinaseA (PKA) inhibitor], but H89 did not affect basal efflux. Onthe other hand, cAMP failed to show any stimulatory effect inhuman macrophages, but basal efflux was inhibitable by H89.In MPMs and THP-1 cells, protein kinase C (PKC) inhibitors blockedcholesterol efflux but had no effect on phospholipid efflux,demonstrating the separation of the regulation of phospholipidefflux and cholesterol efflux in macrophages.
We conclude that: 1) cAMP regulates lipid efflux predominantlyin a PKA-dependent fashion; 2) cholesterol efflux is modulatedby a PKC-dependent mechanism; and 3) mouse and human macrophagesexhibit different modes of regulation of lipid efflux.Supplementary key words cholesterol efflux • macrophage • ATP binding cassette transporter A1 • lipid efflux • regulation
