RGD Reference Report - Role of superoxide radical anion in the mechanism of apoB100 degradation induced by DHA in hepatic cells. - Rat Genome Database

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Role of superoxide radical anion in the mechanism of apoB100 degradation induced by DHA in hepatic cells.

Authors: Andreo, U  Elkind, J  Blachford, C  Cederbaum, AI  Fisher, EA 
Citation: Andreo U, etal., FASEB J. 2011 Oct;25(10):3554-60. doi: 10.1096/fj.11-182725. Epub 2011 Jul 14.
RGD ID: 8655968
Pubmed: (View Article at PubMed) PMID:21757500
DOI: Full-text: DOI:10.1096/fj.11-182725

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 alpha-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.


Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Sod1  (superoxide dismutase 1)

Additional Information