Niacin inhibits surface expression of ATP synthase beta chain in HepG2 cells: implications for raising HDL.
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.
Zhang
Lin-Hua
LH
Atherosclerosis Research Center, Veterans Administration Healthcare System, Long Beach, CA, USA. Linhua.zhang@va.gov
Kamanna
Vaijinath S
VS
Zhang
Michael C
MC
Kashyap
Moti L
ML
D025181:ATP Synthetase Complexes / Q000037:antagonists & inhibitors*; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D005434:Flow Cytometry; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D018613:Microscopy, Confocal; D009525:Niacin / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D008075:Lipoproteins, HDL; D009525:Niacin; D025181:ATP Synthetase Complexes