出版社:American Society for Biochemistry and Molecular Biology
摘要:This study determined the effects of apoA-I, HDL3, or hydroxy-β-cyclodextrin on apoB-100 secretion and bile acid synthesis by HepG2 cells. The principal observations were that: 1 ) ApoB-100 secretion into the medium was significantly less after the addition of any of the three agents. 2 ) Triglyceride mass was not significantly changed from control in the medium but was significantly, although modestly, reduced in the cells. 3 ) Neither free cholesterol (FC) nor cholesteryl ester (CE) mass in the medium was changed; by contrast, CE mass was reduced within the cells although FC was not. 4 ) Although the total mass of cholesterol in the medium was unaffected, the proportion associated with apoB-100 was reduced, whereas the proportion associated with the non-apoB-100 fraction was increased. 5 ) There was also an unanticipated, but substantial, increase in bile acid synthesis induced by apoA-I, HDL3, or hydroxy-β-cyclodextrin, which was time and concentration dependent, and which was associated with marked increases in cholesterol 7α-hydroxylase activity. There were no significant changes in ACAT activity and only modest increases in HMG-CoA reductase activity. These findings support previous clinical observations that an elevated apoB-100 can accompany a low HDL cholesterol in normotriglyceridemic subjects. They also point to physiologically important, although still only partially understood, metabolic relationships amongst hepatic apoB-100 secretion, cholesterol efflux, and bile acid synthesis.