title: The association between angiotensin II-induced free radical generation and membrane fluidity in neutrophils of patients with metabolic syndrome.
abstract: Angiotensin II (Ang II) is able to induce free radical generation in neutrophils, which is more elevated in neutrophils of patients with hypercholesterolemia (HC). In addition, the signal processing through angiotensin I (Ang I) receptors is altered. In present study, we compared the Ang II-triggered free radical generation of neutrophils obtained from patients with relatively isolated forms of metabolic syndrome (MS) with membrane-bound cholesterol content and membrane fluidity. We determined the enhancement of Ang II-induced superoxide anion and leukotriene C(4) (LTC(4)) generation, membrane fluidity and cell-bound cholesterol content of neutrophils obtained from 12 control subjects, 11 patients with obesity (Ob), 10 patients with type 2 diabetes mellitus (t2-DM) and 12 patients with HC. The alteration of signal processing was studied after preincubation with different inhibiting drugs. Superoxide anion, LTC(4) production and membrane rigidity were increased in the following order: control < Ob < t2-DM < HC. Both Ang II-induced superoxide anion and LTC(4) generation were decreased in control cells by pertussis toxin and fluvastatin (Flu), whereas in each patient group, mepacrin, verapamil and Flu were effective, suggesting alterations in signal pathways, which may be attributed to isoprenylation. The enhancement of superoxide anion and LTC(4) generation correlated significantly with membrane rigidity, independently from the experimental groups and membrane-bound cholesterol content. Membrane rigidity of neutrophils, obtained from patients with MS, plays a role in Ang II-induced free radical generation independent of intracellular cholesterol homeostasis.
authors.affiliation: First Department of Medicine, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, Debrecen, H-4012 Hungary.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Seres
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fóris
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Varga
authors.forename: Béla
authors.initials: B
authors.lastname: Kosztáczky
authors.forename: Andrea
authors.initials: A
authors.lastname: Kassai
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Balogh
authors.forename: Péter
authors.initials: P
authors.lastname: Fülöp
authors.forename: György
authors.initials: G
authors.lastname: Paragh
mesh_terms: D000328:Adult; D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D005260:Female; D000077340:Fluvastatin; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism / Q000473:pathology; D007211:Indoles / Q000494:pharmacology; D017997:Leukotriene C4 / Q000378:metabolism; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D037342:Pertussis Toxin / Q000494:pharmacology; D017368:Protein Prenylation / Q000187:drug effects; D011796:Quinacrine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000924:Anticholesteremic Agents; D004791:Enzyme Inhibitors; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D013481:Superoxides; D000804:Angiotensin II; D017997:Leukotriene C4; D000077340:Fluvastatin; D000803:Angiotensin I; D002784:Cholesterol; D014700:Verapamil; D037342:Pertussis Toxin; D011796:Quinacrine