dianas 7(1) > Sanchez etal

dianas | Vol 7 Num 1 | marzo 2018 | e201803b23

Role of unfolding protein response in vascular damage by BPA exposure.

S Sanchez^a, P Reventun, I Cuadrado, R Ramirez, M Saura

a. sandrasanchez07@hotmail.com

III Congreso de Señalización Celular, SECUAH 2018.
20-22 de marzo, 2018. Universidad de Alcalá. Alcalá de Henares, Madrid. España.
Sesión B2 – Fisiología

Resumen

Bisphenol A (BPA) is an organic compound used in the manufacturing of polycarbonate plastics. It is presents in various consumer goods such as food containers, baby and water bottles, and its potential risk to human health has been well characterized. Several epidemiological studies have associated urinary and serum BPA levels in human with various types of cardiovascular diseases including hypertension, heart attack and coronary and peripheral arterial disease. Chronic exposure to BPA has been shown to result in vascular remodelling, atherosclerosis, and altered blood pressure in rodents. In previous studies, we observed that BPA exposure leads to endothelial dysfunction and hypertension in mice by uncoupling eNOS activity, leading to oxidative and nytrosative stress through accumulation of reactive oxygen species (ROS) (Saura et al., 2014). However, molecular mechanisms of BPA toxicity in vascular system are widely unknown. The activation of Unfolding Protein Response (UPR) signaling pathways aims to cope with the stress and plays a pro-survival role in the early stage of atherosclerosis. We propose that BPA induce apoptosis secondary to a prolonged and enhanced (UPR) activation causing tissues damage. To this aim, BPA was orally administrated to mice (150ug/ml in drinking water) for 4 months. We observe vascular remodelling in BPA treated mice comparing to controls. These damages are accompanied by lipid peroxidation, associated with stress, activation of UPR and an extended apoptosis. These results suggest that UPR signalling has an important role in BPA toxicity.