Differential effects of oxidized LDL on apolipoprotein AI and B synthesis in HepG2 cells.
Oxidized low-density lipoproteins (Ox-LDL) are key elements in atherogenesis. Apolipoprotein AI (apoAI) is an active component of the antiatherogenic high-density lipoproteins (HDL). In contrast, plasma apolipoprotein B (apoB), the main component of LDL, is highly correlated with coronary risk. Our results, obtained in HepG2 cells, show that Ox-LDL, unlike native LDL, leads to opposite effects on apoB and apoAI, namely a decrease in apoAI and an increase in apoB secretion as evaluated by [(3)H]leucine incorporation and specific immunoprecipitation. Parallel pulse-chase studies show that Ox-LDL impaired apoB degradation, whereas apoAI degradation was increased and mRNA levels were decreased. We also found that enhanced lipid biosynthesis of both triglycerides and cholesterol esters was involved in the Ox-LDL-induced increase in apoB secretion. Our data suggest that the increase in apoB and decrease in apoAI secretion may in part contribute to the known atherogenicity of Ox-LDL through an elevated LDL/HDL ratio, a strong predictor of coronary risk in patients.
Bourdon
Emmanuel
E
INSERM U498, Dijon, France;-Faculté de Médecine, Université de Bourgogne, 21079 Dijon, France.
Loreau
Nadine
N
Lagrost
Laurent
L
Davignon
Jean
J
Bernier
Lise
L
Blache
Denis
D
D016632:Apolipoprotein A-I / Q000737:chemistry*; D001055:Apolipoproteins B / Q000737:chemistry*; D050197:Atherosclerosis; D002460:Cell Line; D002788:Cholesterol Esters / Q000737:chemistry; D005609:Free Radicals; D006801:Humans; D007930:Leucine / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014280:Triglycerides / Q000737:chemistry
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D002788:Cholesterol Esters; D005609:Free Radicals; D008055:Lipids; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D014280:Triglycerides; C099252:oxidized low density lipoprotein; D007930:Leucine; D010100:Oxygen