Low-dose bisphenol A induces RIPK1-mediated necroptosis in SH-SY5Y cells: Effects on TNF-α and acetylcholinesterase.

Bisphenol A (BPA) is an endocrine disruptor chemical, which is commonly used in everyday products. Adverse effects of its exposure are reported even at picomolar doses. Effects of picomolar and nanomolar concentrations of BPA on cytotoxicity, nitric oxide (NO) levels, acetylcholinesterase (AChE) gene expression and activity, and tumor necrosis factor-α (TNF-α) and caspase-8 levels were determined in SH-SY5Y cells. The current study reveals that low-dose BPA treatment induced cytotoxicity, NO, and caspase-8 levels in SH-SY5Y cells. We also evaluated the mechanism underlying BPA-induced cell death. Ours is the first report that receptor-interacting serine/threonine-protein kinase 1-mediated necroptosis is induced by nanomolar BPA treatment in SH-SY5Y cells. This effect is mediated by altered AChE and decreased TNF-α levels, which result in an apoptosis-necroptosis switch. Moreover, our study reveals that BPA is an activator of AChE.