Involvement of PKC in Induction of ABCAl Expression by Modified LDL

Objective To investigate the role of PKC signaling pathway in ABCA1 expression in murine macrophage induced by oxLDL and acLDL. Methods A murine macrophage cell line, RAW264. 7, were incubated with 100 μg/ml acLDL or oxLDL for 24 h. During this period, PKC agonist (PMA) or antiagonist (GF109203X) were added. The function of ABCA1 was examined by cholesterol efflux experiment, while mRNA and protein level of ABCA1 were detected by semi-quantitative RT-PCR and Western blot, respectively. Results In cells incubated with acLDL, 1.0 μmol/L GF109203X reduced cholesterol efflux to 56. 0% , ABCA1 mRNA to (54. 0±8. 2)% , and ABCA1 protein to (68. 1±2. 0)% , respectively, compared with control. The same reactions were seen when cells were incubated with oxLDL and 1. 0μmol/L GF109203X, with cholesterol efflux decreased to 47. 0% , and ABCA1 mRNA decreased to (43.0±5.0)% , and ABCA1 protein to (73.0±10. 0)% , respectively. Conversely, 160 nmol/L PMA increased cholesterol efflux to a maximum of 134. 0% in acLDL group and 125. 1% in oxLDL group. And PMA also increased AB-CA1 mRNA to (211. 0± 17. 0)% , ABCA1 protein to (305. 0±21. 0)% , respectively, compared with control. Conclusions PKC signaling pathway is involved in the regulation of ABCA1 expression in murine macrophages induced by acLDL and oxLDL. Activation of PKC signaling results in up-regulation of ABCA1 expression and enhances ABCA1-mediated cholesterol efflux in macrophages.