Niacin inhibits surface expression of ATP synthase β chain in HepG2 cells: implications for raising HDL
2008
Lin-Hua Zhang | Vaijinath S. Kamanna | Michael C. Zhang | Moti L. Kashyap
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.
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