Bisphenol A Induces Accelerated Cell Aging in Murine Endothelium

Area of Science:

• Endocrinology
• Cell Biology
• Cardiovascular Science

Background:

• Bisphenol A (BPA) is a known endocrine disruptor with detrimental effects on multiple organ systems.
• Previous research indicated BPA induces necroptosis in murine aortic endothelial cells (MAECs).
• The potential role of BPA in inducing endothelial cell senescence remained unexplored.

Purpose of the Study:

• To investigate the involvement of senescence mechanisms in BPA-induced endothelial cell dysfunction.
• To elucidate the specific pathways and molecular markers associated with BPA-induced senescence.
• To evaluate the protective effects of N-acetylcysteine (NAC) against BPA-induced senescence.

Main Methods:

• Cellular senescence was assessed using β-Gal assays in MAECs exposed to varying BPA concentrations.
• Western blot analysis was employed to quantify the expression of senescence markers (p16, p21) and UPR pathway proteins (PERK, ATF4, CHOP).
• Quantitative PCR (qPCR) was used to further analyze UPR pathway gene expression.
• In vivo studies involved treating mice with BPA and analyzing endothelial tissue for senescence markers.
• The impact of NAC pretreatment on BPA-induced senescence and UPR activation was examined.

Main Results:

• BPA exposure, even at low doses (100 nM, 5 µM), induced significant cellular senescence in MAECs.
• Overexpression of senescence-associated proteins p16 and p21 was observed in BPA-treated cells.
• The unfolded protein response (UPR), specifically the PERK-ATF4-CHOP pathway, was activated by BPA.
• In vivo studies confirmed increased p16, p21, and CHOP expression in the endothelium of BPA-treated mice.
• NAC pretreatment significantly reduced BPA-induced senescence, protein overexpression, and UPR activation.

Conclusions:

• BPA actively promotes accelerated cell aging and senescence in vascular endothelial cells.
• Oxidative stress induced by BPA triggers UPR activation, contributing to the senescent phenotype.
• BPA-induced endothelial senescence and UPR activation are implicated in the development of cardiovascular diseases.
• NAC demonstrates a protective effect against BPA-induced endothelial damage, suggesting a potential therapeutic strategy.