The effect of compounds associated with cigarette smoking on the secretion of lipoprotein lipid by HepG2 cells.
Cigarette smoking is associated with significant alterations in serum levels of lipids and lipoproteins, however the biochemical mechanisms responsible for this effect are poorly understood. One possibility is that compounds which are present (nicotine) or elevated (free fatty acid, epinephrine, cortisol) in the blood of smokers might contribute to the observed effects by modulating hepatic lipoprotein secretion. The human hepatoma cell line HepG2 was used as a model system to investigate this question. Pre-incubation of the cells for 24 h with 1 mM oleate caused increases in VLDL cholesterol secretion (0.27 to 0.37 micrograms/mg cell protein/24 h, P < 0.01) and decreases in LDL and HDL cholesterol secretion (1.0 to 0.7 micrograms/mg cell protein/24 h, P < 0.02 and 4.1 to 2.5 micrograms/mg cell protein/24 h, P < 0.02, respectively). Incubation with 1.0 microM dexamethasone caused an increase in HDL cholesterol secretion (2.46 to 3.83 micrograms/mg cell protein/24 h, P < 0.05), whereas incubation with 1.0 microM epinephrine caused an increase in LDL cholesterol secretion (0.9 to 1.8 micrograms/mg cell protein/24 h, P < 0.01). Incubation with either dexamethasone or epinephrine caused significant increases in total media cholesterol (P < 0.02), whereas preincubation with oleate did not. Nicotine (10 microM) did not affect lipoprotein lipid secretion. In conclusion, the effects of oleate and epinephrine on the lipoprotein lipid levels secreted by HepG2 cells were consistent with the altered serum lipoprotein levels observed in smokers, while the effects of dexamethasone, a cortisol analogue, were not.
Craig
W Y
WY
Foundation for Blood Research, Scarborough, ME 04070-0190.
D002499:Centrifugation, Density Gradient; D002784:Cholesterol / Q000032:analysis; D003907:Dexamethasone / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D008074:Lipoproteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D012907:Smoking / Q000097:blood / Q000378:metabolism*; D014280:Triglycerides / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D008074:Lipoproteins; D009829:Oleic Acids; D014280:Triglycerides; D019301:Oleic Acid; D009538:Nicotine; D003907:Dexamethasone; D002784:Cholesterol; D004837:Epinephrine