Albumin inhibits apolipoprotein AI and AII production in human hepatoblastoma cell line (Hep G2): additive effects of oleate-albumin complex.
Although the role of multiple humoral agents (such as plasma albumin, glucose, hormones etc.) are implicated in lipoprotein metabolism, the mechanism of action of these agents on various steps of the synthesis and secretion of lipoproteins and apolipoproteins (protein moieties of lipoproteins) are not completely understood. Specifically, the hepatocellular mechanisms of the effect of albumin and fatty acids on apolipoprotein (apo) AI and AII [major proteins of high density lipoproteins (HDL)] synthesis and secretion are not known. Using human hepatoblastoma cells (Hep G2) as an in vitro model system, this study examined the effect of albumin and fatty acids on the synthesis, secretion, and the steady-state mRNA expression of apo AI and AII. The data indicated that the incubation of Hep G2 cells with albumin, dose-dependently, inhibited apo AI and AII accumulation (secretion) in the media, de novo synthesis, and the steady-state mRNA expression. Albumin did not alter total protein synthesis; thus the effect of albumin appeared to be specific for the synthesis and secretion of apo AI and apo AII. Free fatty acids (FFA) are transported by albumin and diseases characterized by enhanced FFA mobilization (e.g. diabetes mellitus) are associated with low HDL levels. Studies were therefore performed to examine the effect of albumin-bound-oleic acid on apo AI and apo AII production. The results showed that the albumin-oleate complex further increased the inhibitory effects of albumin on apo AI and apo AII production. These data suggest how HDL metabolism may be affected at the hepatocellular level by alterations in plasma albumin concentrations and/or fatty acid mobilization in clinical situations characterized by altered HDL levels.
Sakai
T
T
Department of Veterans Affairs Healthcare System, Cholesterol Research Center, 5901 E. Seventh Street (111GE), Long Beach, CA 90822, USA.
Jin
F Y
FY
Kamanna
V S
VS
Kashyap
M L
ML
D000418:Albumins / Q000494:pharmacology*; D016632:Apolipoprotein A-I / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D016633:Apolipoprotein A-II / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018197:Hepatoblastoma / Q000737:chemistry; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry; D019301:Oleic Acid / Q000494:pharmacology*; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
D000418:Albumins; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D012333:RNA, Messenger; D019301:Oleic Acid