Abstract
Bisphenol A (BPA) is a widespread endocrine disruptor affecting many organs and systems. Previous work in our laboratory demonstrated that BPA could induce death due to necroptosis in murine aortic endothelial cells (MAECs). This work aims to evaluate the possible involvement of BPA-induced senescence mechanisms in endothelial cells. The β-Gal assays showed interesting differences in cell senescence at relatively low doses (100 nM and 5 µM). Western blots confirmed that proteins involved in senescence mechanisms, p16 and p21, were overexpressed in the presence of BPA. In addition, the UPR (unfolding protein response) system, which is part of the senescent phenotype, was also explored by Western blot and qPCR, confirming the involvement of the PERK-ATF4-CHOP pathway (related to pathological processes). The endothelium of mice treated with BPA showed an evident increase in the expression of the proteins p16, p21, and CHOP, confirming the results observed in cells. Our results demonstrate that oxidative stress induced by BPA leads to UPR activation and senescence since pretreatment with N-acetylcysteine (NAC) in BPA-treated cells reduced the percentage of senescent cells prevented the overexpression of proteins related to BPA-induced senescence and reduced the activation of the UPR system. The results suggest that BPA participates actively in accelerated cell aging mechanisms, affecting the vascular endothelium and promoting cardiovascular diseases.
Highlights
Bisphenol A (BPA) is a phenolic-type molecule widely used in the manufacture of plastics
Only the PERK‐ATF4‐CHOP branch of unfolding protein response (UPR) is activated in the vascular endo‐
For the first time, that BPA in doses under the cytotoxic threshold can induce accelerated cell aging in mouse aortic endothelium
Summary
Bisphenol A (BPA) is a phenolic-type molecule widely used in the manufacture of plastics. BPA is classified as an endocrine disruptor or xenoestrogen due to its ability to bind to estrogen receptors [9]. For this reason, numerous studies are exploring its possible effects on both the female and male genitourinary systems [10,11,12,13]. In the last two decades, evidence correlates BPA with other types of pathologies such as diabetes, obesity, and even cognitive and behavioral disorders [14,15,16,17]. Few studies explore the cardiovascular system, but there are population studies that correlate high concentrations of urinary BPA with an increased risk of developing arterial hypertension [22,23]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
