Ação molecular da 1,25(OH)2D3 em células endoteliais humanas submetidas a diferentes concentrações de leptina

Abstract

High plasma concentrations of leptin have been related to increased formation of reactive oxygen species (ROS) that can play a central regulatory role in inflammatory and cardiovascular events. Recent studies have shown that vitamin D is able to reduce oxidative stress markers, as well as interfere with the production of inflammatory cytokines. The aim of this study was to evaluate the effect of pre-treatment with physiological (10-10 M) and supraphysiological (10-7 M) concentrations of 1,25(OH)2D3 in the production of superoxide anion (O2) and transcription factors NF-κB and Nrf2 in human endothelial cells stimulated with different leptin concentrations (1 and 10 ng/mL). When cells were pre-treated with 1,25(OH)2D3, and were stimulated with leptin (1 and 10 ng/mL), 1,25(OH)2D3 reduced (p <0.05) superoxide anion production (O2), especially atthe concentration of 10-7 M. The NF-κB transcription factor has been positively activated in cells incubated with 10 ng/mL of leptin, however, when using the pre-treatment with 1,25(OH)2D3 decreased the translocation of NF-κB as well as the production of cytokines regulated by this transcription factor. It was also observed that the pre-treatment with 10-7 M of 1,25(OH)2D3 increased significantly (p<0.05) the expression of transcription factor Nrf2 in nuclear fraction compared to control, particularly when associated with 10 ng/mL leptin (p<0.05). Taken together, our results indicate that treatment with both concentrations, 10-10 and 10-7 M, of 1,25(OH)2D3 in endothelial human cells were effective in inhibiting the production of superoxide anion (O2), pro-inflammatory cytokines and inhibit the nuclear translocation of the transcription factor NF-κB, as well as activate the antioxidant Nrf2 pathway. These findings suggest that pre-treatment with with both concentrations (physiological and supraphysiological) of 1,25(OH)2D3 in the presence of high concentration of leptin, can have a positive effect on the endothelium through the regulation of markers of inflammation and antioxidant activity