Biogenesis of apolipoprotein A-V and its impact on VLDL triglyceride secretion
| Autor: | Melissa A. Fabritius, Gregory S. Shelness, Li Hou, Richard B. Weinberg, Anna M. Blade |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Very low-density lipoprotein
Apolipoprotein B QD415-436 CHO Cells Lipoproteins VLDL Transfection Biochemistry Endocrinology Cricetulus Liver Neoplasms Experimental Lipid droplet Cricetinae polycyclic compounds apolipoprotein B Animals Secretion Secretory pathway Triglycerides Research Articles biology lipoprotein assembly Chinese hamster ovary cell nutritional and metabolic diseases Cell Biology Cell biology Rats Apolipoproteins Cell culture Apolipoprotein A-V lipid trafficking biology.protein lipids (amino acids peptides and proteins) Intracellular Oleic Acid |
| Zdroj: | Journal of Lipid Research, Vol 52, Iss 2, Pp 237-244 (2011) |
| ISSN: | 1539-7262 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|