出版社:American Society for Biochemistry and Molecular Biology
摘要:Niacin is an effective agent for raising HDL, but its cellular target sites are largely unknown. We examined effects of niacin on the surface expression of ATP synthase β chain, a newly described HDL/apolipoprotein A-I (apoA-I) receptor for HDL endocytosis, in HepG2 cells. A significant amount of immunodetectable β chain was observed on the surface of HepG2 cells, which was competitively displaced by apoA-I. Niacin treatment reduced the surface expression of β chain in HepG2 cells by ∼27%, and decreased 125I-labeled HDL uptake up to ∼35%. However, nicotinamide, a niacin metabolite that does not have clinical lipid effects, exhibited weaker inhibition on the β chain cell surface expression, and failed to show inhibitory action on 125I-labeled HDL uptake. Furthermore, anti-β chain antibody significantly reduced 125I-labeled HDL uptake and abolished the inhibitory effect of niacin. Niacin did not change β chain mRNA expression. These data suggest that niacin inhibits cell surface expression of the ATP synthase β chain, leading to reduced hepatic removal of HDL protein, thus implicating a potential cellular target for niacin action to raise HDL.