Niacin inhibits surface expression of ATP synthase beta chain in HepG2 cells: implications for raising HDL.

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Zhang LH, Kamanna VS, Zhang MC, Kashyap ML

Niacin inhibits surface expression of ATP synthase beta chain in HepG2 cells: implications for raising HDL.

J Lipid Res. 2008 Jun;49(6):1195-201. doi: 10.1194/jlr.M700426-JLR200. Epub 2008 Mar 3.

PubMed ID

18316796 [ View in PubMed

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Abstract

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 beta chain, a newly described HDL/apolipoprotein A-I (apoA-I) receptor for HDL endocytosis, in HepG2 cells. A significant amount of immunodetectable beta chain was observed on the surface of HepG2 cells, which was competitively displaced by apoA-I. Niacin treatment reduced the surface expression of beta chain in HepG2 cells by approximately 27%, and decreased (125)I-labeled HDL uptake up to approximately 35%. However, nicotinamide, a niacin metabolite that does not have clinical lipid effects, exhibited weaker inhibition on the beta chain cell surface expression, and failed to show inhibitory action on (125)I-labeled HDL uptake. Furthermore, anti-beta chain antibody significantly reduced (125)I-labeled HDL uptake and abolished the inhibitory effect of niacin. Niacin did not change beta chain mRNA expression. These data suggest that niacin inhibits cell surface expression of the ATP synthase beta chain, leading to reduced hepatic removal of HDL protein, thus implicating a potential cellular target for niacin action to raise HDL.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Inositol nicotinate	ATP synthase subunit beta, mitochondrial	Protein	Humans	No	Inhibitor	Details