title: Differential effects of apolipoprotein E3 and E4 on markers of oxidative status in macrophages.
abstract: ApoE is secreted by macrophages at the lesion site of the atherosclerotic plaque, where it is thought to play a protective role against atherosclerosis independently of its effects on lipid metabolism. Of the three common isoforms for apoE, apoE4 is associated with higher risk of cardiovascular disease (CVD). In vitro studies have shown that recombinant apoE may act as an antioxidant in an isoform-dependent manner (E2 > E3 > E4). The oxidative status of the macrophages plays a key role in the process of atherosclerosis. In the present study the possible differential actions of apoE3 and apoE4 on several parameters of oxidative status were determined in stably transfected murine macrophages (RAW 264-7-apoE3 and - apoE4). No differences between genotypes were observed after peroxide challenge in either protection against cytotoxicity or in cell membrane oxidation, and modest differences were observed in the non-enzymatic antioxidants (glutathione and alpha-tocopherol) in apoE3 v. apoE4 macrophages. Importantly, cells secreting apoE4 showed increased membrane oxidation under basal conditions, and produced more NO and superoxide anion radicals than the apoE3 macrophages after stimulation. The present data suggest that apoE genotype influences the oxidative status of macrophages, and this could partly contribute to the higher CVD risk observed in apoE4 carriers.
authors: Institute of Human Nutrition and Food Science, Christian Albrechts University of Kiel, Hermann-Rodewald-Strasse 6, 24098 Kiel, Germany.
authors: Laia
authors: L
authors: Jofre-Monseny
authors: Sonia
authors: S
authors: de Pascual-Teresa
authors: Eva
authors: E
authors: Plonka
authors: Patricia
authors: P
authors: Huebbe
authors: Christine
authors: C
authors: Boesch-Saadatmandi
authors: Anne-Marie
authors: AM
authors: Minihane
authors: Gerald
authors: G
authors: Rimbach
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D053318:Apolipoprotein E3 / Q000235:genetics / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics / Q000378:metabolism*; D001896:Boron Compounds / Q000378:metabolism; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004396:Coloring Agents / Q000378:metabolism; D005838:Genotype; D005978:Glutathione / Q000032:analysis; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D013481:Superoxides / Q000378:metabolism; D014810:Vitamin E / Q000032:analysis; D024502:alpha-Tocopherol / Q000494:pharmacology
chemical_list: D000963:Antimetabolites; D000975:Antioxidants; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001896:Boron Compounds; C120421:C11-BODIPY(581-591); D004396:Coloring Agents; D013481:Superoxides; D014810:Vitamin E; D009569:Nitric Oxide; D019328:Buthionine Sulfoximine; D005978:Glutathione; D024502:alpha-Tocopherol