Please use this identifier to cite or link to this item:
https://observatorio.fm.usp.br/handle/OPI/10012
Title: | Testosterone induces leucocyte migration by NADPH oxidase-driven ROS- and COX2-dependent mechanisms |
Authors: | CHIGNALIA, Andreia Z.; OLIVEIRA, Maria Aparecida; DEBBAS, Victor; DULL, Randal O.; LAURINDO, Francisco R. M.; TOUYZ, Rhian M.; CARVALHO, Maria Helena C.; FORTES, Zuleica B.; TOSTES, Rita C. |
Citation: | CLINICAL SCIENCE, v.129, n.1, p.39-48, 2015 |
Abstract: | The mechanisms whereby testosterone increases cardiovascular risk are not clarified. However, oxidative stress and inflammation seem to be determinants. Herein, we sought to determine whether exogenous testosterone, at physiological levels, induces leucocyte migration, a central feature in immune and inflammatory responses and the mediating mechanisms. We hypothesized that testosterone induces leucocyte migration via NADPH oxidase (NADPHox)-driven reactive oxygen species (ROS) and cyclooxygenase (COX)-dependent mechanisms. Sixteen-week-old Wistar rats received an intraperitoneal injection (5 ml) of either testosterone (10(-7) mol/l) or saline. Rats were pre-treated with 5 ml of sodium salicylate (SS, non-selective COX inhibitor, 1.25x10(-3) mol/l, 1 h prior to testosterone or saline), flutamide (androgen receptor antagonist, 10 (5) mol/l), apocynin (NADPHox inhibitor, 3x10(-4) mol/l), N-[2-Cyclohexyloxy-4-nitrophenyl] methanesulfonamide (NS398, COX2 inhibitor, 10(-4) mol/l) or saline, 4 h before testosterone or saline administration. Leucocyte migration was assessed 24 h after testosterone administration by intravital microscopy of the mesenteric bed. Serum levels of testosterone were measured by radioimmunoassay. NADPHox activity was assessed in membrane fractions of the mesenteric bed by dihydroethidium (DHE) fluorescence and in isolated vascular smooth muscle cells (VSMC) by HPLC. NADPHox subunits and VCAM (vascular cell adhesion molecule) expression were determined by immunoblotting. Testosterone administration did not change serum levels of endogenous testosterone, but increased venular leucocyte migration to the adventia, NADPHox activity and expression (P<0.05). These effects were blocked by flutamide. SS inhibited testosterone-induced leucocyte migration (P<0.05). Apocynin and NS398 abolished testosterone-induced leucocyte migration and NADPHox activity (P<0.05). Testosterone induces leucocyte migration via NADPHox-and COX2-dependent mechanisms and may contribute to inflammatory processes and oxidative stress in the vasculature potentially increasing cardiovascular risk. |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - FM/MCP Artigos e Materiais de Revistas Científicas - HC/InCor Artigos e Materiais de Revistas Científicas - LIM/19 |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
art_CHIGNALIA_Testosterone_induces_leucocyte_migration_by_NADPH_oxidasedriven_ROS_2015.PDF Restricted Access | publishedVersion (English) | 455.73 kB | Adobe PDF | View/Open Request a copy |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.