Association between Angiotensin II-Induced Free Radical Generation and Membrane Fluidity in Neutrophils of Patients with Metabolic Syndrome

• Published in: The Journal of membrane biology Vol. 214; no. 1-2; pp. 91 - 98
• Main Authors: Seres, Ildikó, Fóris, Gabriella, Varga, Zsuzsa, Kosztáczky, Béla, Kassai, Andrea, Balogh, Zoltán, Fülöp, Péter, Paragh, György
• Format: Journal Article
• Language: English
• Published: United States New York : Springer-Verlag 01.11.2006; Springer Nature B.V
• Subjects: Adult; Angiotensin I - pharmacology; angiotensin II; Angiotensin II - pharmacology; Anticholesteremic Agents - pharmacology; Cellular biology; Cholesterol; Cholesterol - metabolism; Diabetes; Diabetes Mellitus, Type 2 - metabolism; Enzyme Inhibitors - pharmacology; Fatty Acids, Monounsaturated - pharmacology; Female; Free radical; Homeostasis - drug effects; Humans; Hypercholesterolemia - metabolism; Hypercholesterolemia - pathology; Indoles - pharmacology; Inhibitor drugs; Leukotriene C4 - metabolism; Male; membrane fluidity; Membrane Fluidity - drug effects; Membranes; Metabolic syndrome; Metabolic Syndrome - metabolism; Metabolic Syndrome - pathology; Middle Aged; Neutrophil; Neutrophils - metabolism; Neutrophils - pathology; Pertussis Toxin - pharmacology; Protein Prenylation - drug effects; Quinacrine - pharmacology; Signal Transduction - drug effects; Superoxides - metabolism; Vasoconstrictor Agents - pharmacology; Vasodilator Agents - pharmacology; Verapamil - pharmacology
• ISSN: 0022-2631; 1432-1424
• DOI: 10.1007/s00232-006-0020-7

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 C₄ (LTC₄) 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, LTC₄ production and membrane rigidity were increased in the following order: control < Ob < t2-DM < HC. Both Ang II-induced superoxide anion and LTC₄ 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 LTC₄ 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.