Involvement of oxysterols and lysophosphatidylcholine in the oxidized LDL-induced impairment of serum albumin synthesis by HEPG2 cells.
Oxidized low density lipoproteins (Ox-LDLs) are increasingly thought to be a key element in atherogenesis. We have previously reported that serum albumin has important antioxidant properties and that a reduced synthesis of albumin may represent a crucial point in the overall antioxidant defense. In the present work, we aimed at determining whether Ox-LDL could modulate albumin synthesis in cultured human hepatocytes (HepG2 cells). With the use of enzyme immunoassay and radiolabeled leucine incorporation followed by specific immunoprecipitation, Ox-LDL was found to lead to a dose-dependent decrease in albumin secretion. Moreover, the protein synthesis and mRNA levels were decreased in the presence of Ox-LDL, as assessed by Northern blot analysis. Because oxysterols and lysophospholipids are key components of Ox-LDL, we tested the effects of oxysterols (7-ketocholesterol and 25-hydroxycholesterol) and lysophosphatidylcholine on albumin secretion and expression. In our experimental conditions, we found that incubations with oxysterols or lysophosphatidylcholine at pathophysiological concentrations similar to those measured in Ox-LDLs reproduced the above-mentioned inhibitory effects on albumin synthesis. On the basis of our in vitro data, we propose that this newly described biological effect of Ox-LDL might partly explain the findings of epidemiological studies indicating that reduced levels of serum albumin are associated with increased mortality.
Bourdon
E
E
INSERM U498, Biochimie des Lipoprotéines et Interactions Vasculaires, Université de Bourgogne, Dijon, France.
Loreau
N
N
Davignon
J
J
Bernier
L
L
Blache
D
D
D000975:Antioxidants / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000378:metabolism; D007653:Ketocholesterols / Q000494:pharmacology; D007930:Leucine / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D012709:Serum Albumin / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D013997:Time Factors; D014316:Tritium; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D006888:Hydroxycholesterols; D007653:Ketocholesterols; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D012333:RNA, Messenger; D012709:Serum Albumin; C099252:oxidized low density lipoprotein; D014316:Tritium; C007997:25-hydroxycholesterol; D007930:Leucine; C003001:7-ketocholesterol