Oxidative modification of low-density lipoprotein by the human hepatoma cell line HepG2.
The human hepatoblastoma cell line HepG2 is a liver model commonly used for lipid metabolism studies. Numerous cell types have been found to oxidize low-density lipoprotein (LDL) but, to our knowledge, the effects of HepG2 cells on LDL have not been investigated. We found that LDL is modified by HepG2 cells through a peroxidative mechanism, as judged by an increase in TBARS content (which was prevented in the presence of the antioxidants vitamin E, 2,6-di-tertbutyl-cresol and probucol), increased degradation by J774 macrophages, decreased internalization by MRC5 fibroblasts, and aggregation of apo B. Aspirin and allopurinol, which inhibit cyclooxygenase and xanthine-oxidase activities, respectively, had no effect on HepG2-induced LDL modification, and neither did catalase, which dismutates hydrogen peroxide; or mannitol, which scavenges hydroxyl radicals. In contrast, superoxide dismutase, a superoxide anion scavenger, and glutamate and threonine, which alter cellular cystine uptake, prevented LDL modifications, as did the removal of cysteine/cystine from the culture medium. Oxidation of LDL by HepG2 cells might thus involve superoxide anion production and/or thiol metabolism.
Pico
I
I
Laboratoire de Biochimie Appliquée des Sciences Pharmaceutiques et Biologiques, Châtenay-Malabry, France.
Myara
I
I
Pech-Amsellem
M A
MA
Vedie
B
B
Chappey
B
B
Moatti
N
N
D000975:Antioxidants / Q000494:pharmacology; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002852:Chromatography, Ion Exchange; D004587:Electrophoresis, Agar Gel; D004591:Electrophoresis, Polyacrylamide Gel; D018197:Hepatoblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D011341:Probucol / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D014810:Vitamin E; D002084:Butylated Hydroxytoluene; D011341:Probucol