1. Contribution of D4-F to ABCA1 expression and cholesterol efflux in THP-1 macrophage-derived foam cells
- Author
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Kai Yin, Ji Xiao, Li-Bao Cui, Jin Jiang, Duan-Fang Liao, Chao-Ke Tang, Chun-Zhi Tan, Xie-Hong Liu, Zhong-Cheng Mo, and Ya-Ling Tang
- Subjects
Small interfering RNA ,Time Factors ,Gene Expression ,Cell Line ,chemistry.chemical_compound ,polycyclic compounds ,Cyclic AMP ,Serine ,Humans ,Cyclic adenosine monophosphate ,cardiovascular diseases ,RNA, Messenger ,Phosphorylation ,Protein kinase A ,cdc42 GTP-Binding Protein ,Pharmacology ,biology ,Apolipoprotein A-I ,Reverse cholesterol transport ,nutritional and metabolic diseases ,hemic and immune systems ,Biological Transport ,Cyclic AMP-Dependent Protein Kinases ,Cell biology ,Up-Regulation ,Enzyme Activation ,ATP Binding Cassette Transporter 1 ,Cholesterol ,chemistry ,Biochemistry ,ABCA1 ,biology.protein ,lipids (amino acids, peptides, and proteins) ,ATP-Binding Cassette Transporters ,Efflux ,Cardiology and Cardiovascular Medicine ,Foam Cells ,Signal Transduction - Abstract
Adenosine triphosphate-binding cassette transporter A1 (ABCA1) plays a crucial role in apolipoprotein A-I (apoA-I) binding activity and promotes cellular cholesterol efflux. ApoA-I mimetic peptide D4-F has reported to have the similar ability as apoA-I. However, the detailed mechanisms of ABCA1 regulation by D4-F are not understood. In the present study, we investigated the effects of D4-F on ABCA1 expression and ABCA1-dependent cholesterol efflux and examined the role of Cdc42/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway on the regulation of ABCA1 by D4-F in THP-1 macrophage-derived foam cells. Results showed that D4-F stabilized ABCA1 protein and enhanced ABCA1-dependent cholesterol efflux but had no effect on ABCA1 messenger RNA expression. We also revealed that D4-F enhanced cAMP level and PKA activity and ABCA1 serine phosphorylation. Short interfering RNA of PKA led to reduction of ABCA1 serine phosphorylation and ABCA1-mediated cholesterol efflux compensated by D4-F. PKA-specific activation by PKA agonist enhanced the upregulation of ABCA1 serine phosphorylation and ABCA1-mediated cholesterol efflux by D4-F. However, ABCA1 expression did not change by treatment with PKA agonist or PKA-short interfering RNA. We found that secramine B of Cdc42 inhibitor reduced the cAMP level compensated by D4-F. These results provide evidence that D4-F enhances ABCA1 serine phosphorylation and ABCA1-dependent cholesterol efflux through Cdc42/cAMP/PKA pathway in THP-1 macrophage-derived foam cells.
- Published
- 2010