Curcumin regulates the metabolism of low density lipoproteins by improving the C-to-U RNA editing efficiency of apolipoprotein B in primary rat hepatocytes

Abstract

There are two isoforms of apolipoprotein B (apoB) in mammals: apoB-100 and apoB-48. The latter is generated by C-to-U editing of apoB mRNA, catalyzed by the apolipoprotein B mRNA editing enzyme, namely, catalytic polypeptide 1 (APOBEC-1). Lipid particles containing apoB-48 are cleared from the plasma more rapidly than those containing apoB-100 and thus do not contribute to plaque formation in the arterial wall. In the present study, we analyzed whether curcumin is capable of regulating lipid metabolism by improving the level of apoB mRNA editing. The cytotoxicity of curcumin in hepatocytes was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the levels of APOBEC-1 mRNA and protein were analyzed by real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting. The efficiency of apoB mRNA editing was determined by reverse transcription PCR (RT-PCR) products and cloning sequencing analysis. We demonstrated that curcumin concentrations up to 70 μM had no significant cytotoxic effects on primary rat hepatocytes at 24 h. At 15 μM, curcumin significantly increased the expression of APOBEC-1 mRNA and protein, and increased the editing level of apoB mRNA from 3.13 to 7.53%. At 25 μM, curcumin reduced the expression of APOBEC-1; however, it did not affect the apoB mRNA editing level. Our data suggested that curcumin at a concentration of 15 μM raised the level of apoB-48 and reduced the level of apoB-100 by increasing the expression of APOBEC-1 in primary rat hepatocytes; therefore, curcumin may be a novel preventative therapy for atherosclerosis.