Document Detail

Biogenesis of apolipoprotein A-V and its impact on VLDL triglyceride secretion.
MedLine Citation:
PMID:  21115968     Owner:  NLM     Status:  MEDLINE    
Apolipoprotein A-V (apoA-V) is a potent regulator of intravascular triglyceride (TG) metabolism, yet its plasma concentration is very low compared with that of other apolipoproteins. To examine the basis for its low plasma concentration, the secretion efficiency of apoA-V was measured in stably transfected McA-RH7777 rat hepatoma cells. Pulse-chase experiments revealed that only ∼20% of newly synthesized apoA-V is secreted into culture medium within 3 h postsynthesis and that ∼65% undergoes presecretory turnover; similar results were obtained with transfected nonhepatic Chinese hamster ovary cells. ApoA-V secreted by McA-RH7777 cells was not associated with cell surface heparin-competable binding sites. When stably transfected McA-RH7777 cells were treated with oleic acid, the resulting increase in TG synthesis caused a reduction in apoA-V secretion, a reciprocal increase in cell-associated apoA-V, and movement of apoA-V onto cytosolic lipid droplets. In a stably transfected doxycycline-inducible McA-RH7777 cell line, apoA-V expression inhibited TG secretion by ∼50%, increased cellular TG, and reduced Z-average VLDL(1) particle diameter from 81 to 67 nm; however, no impact on apoB secretion was observed. These data demonstrate that apoA-V inefficiently traffics within the secretory pathway, that its intracellular itinerary can be regulated by changes in cellular TG accumulation, and that apoA-V synthesis can modulate VLDL TG mobilization and secretion.
Anna M Blade; Melissa A Fabritius; Li Hou; Richard B Weinberg; Gregory S Shelness
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-11-26
Journal Detail:
Title:  Journal of lipid research     Volume:  52     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-17     Completed Date:  2011-05-05     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  237-44     Citation Subset:  IM    
Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
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MeSH Terms
Apolipoproteins / biosynthesis*,  metabolism
CHO Cells
Lipoproteins, VLDL / secretion*
Liver Neoplasms, Experimental / metabolism
Oleic Acid / metabolism
Triglycerides / secretion*
Grant Support
Reg. No./Substance:
0/Apoa5 protein, rat; 0/Apolipoproteins; 0/Lipoproteins, VLDL; 0/Triglycerides; 0/very low density lipoprotein triglyceride; 112-80-1/Oleic Acid

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