Premium
Role of superoxide radical anion in the mechanism of apoB100 degradation induced by DHA in hepatic cells
Author(s) -
Andreo Ursula,
Elkind Josh,
Blachford Courtney,
Cederbaum Arthur I.,
Fisher Edward A.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.11-182725
Subject(s) - chemistry , superoxide , biochemistry , lipid peroxidation , docosahexaenoic acid , apolipoprotein b , superoxide dismutase , tbars , very low density lipoprotein , polyunsaturated fatty acid , oxidative stress , fatty acid , cholesterol , lipoprotein , enzyme
VLDL is produced by the liver. Its major protein is apoB100. Docosahexaenoic acid (DHA), a dietary polyunsaturated fatty acid (PUFA), reduces VLDL levels and is used therapeutically for hypertriglyceridemia. In model systems, DHA lowers VLDL secretion by inducing presecretory apoB100 degradation, a process dependent on PUFA‐derived lipid peroxides. We hypothesized that superoxide (SO) was a major participant in DHA‐induced apoB100 degradation, given its promotion of lipid peroxidation. SO levels in a model of VLDL metabolism, rat hepatoma McArdle cells, were either decreased by a mimetic of superoxide dismutase 1 (SOD1) or by overexpressing SOD1 or increased by SOD1 siRNA. ApoB100 recovery was assessed by immunoprecipitation, SO by 2‐hydroxyethidine, and lipid peroxides by thiobarbituric acid reactive substances. The SOD1 mimetic or SOD1 overexpression reduced SO and inhibited apoB100 degradation in DHA‐treated cells by up to 100%. Surprisingly, silencing SOD1 did not increase DHA‐induced degradation, although levels of SO were higher (+44%); those of lipid peroxides were similar, and their reduction by α‐tocopherol decreased degradation by 50%. SO is required for lipid peroxidation in DHA‐induced apoB100 degradation, but it is the peroxide level that has a tighter relationship to the level of degradation and the regulation of VLDL production.—Andreo, U., Elkind, J., Blachford, C., Cederbaum, A. I., Fisher, E. A. Role of superoxide radical anion in the mechanism of apoB100 degradation induced by DHA in hepatic cells. FASEB J. 25, 3554–3560 (2011). www.fasebj.org