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

Abstract

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.

Neurotoxic effects of bisphenol A on SH-SY5Y neuroblastoma cells via nitric oxide

“…Our results distincly show that different doses (0-100 μM) of BPA administered for different period may change viability and NO levels of SH-SY5Y neuroblastoma cells. Our group recently published that NO plays a role in cytotoxicity of low dose BPA in SH-SY5Y neuroblastoma cells [18]. Additionally, it has been shown that NO induces cell death mechanisms in other type of neuroblastoma cell lines [19,20] These observations clarify the fact that doses of BPA at levels 0.05mg/kgbody weight/day, which for a long time was thought by EFSA to be safe, is toxic for the SH-SY5Y neuroblastoma cells.…”

“…Neurotoxic effects of low dose BPA exposure on SH-SY5Y neuroblastoma cells may be explained with increase in the levels of NO as a result from different parameters. Previous report of Ayazgok et al showed that nNOS mRNA level was not changed by low dose BPa treatment in SH-SY5Y neuroblastoma cells [18]…”

Protective role of selenium against bisphenol-A induced oxidative stress, cytokine generation and apoptosis in SH-SY5Y neuronal cell line

“…Thus, many institutions and organizations are now looking for ways to reduce the damage caused by BPH-A. In a recent study, it was stated that NO, Caspaze-8 and cytotoxicity increased in the neuroblastoma cell line after low-dose BPH-A exposure (Ayazgok et al, 2018). Guzel et al, conducted that there was an increase in intracellular Ca 2+ ion, apoptosis, and mitochondrial oxidative stress in MCF-7 cells after exposure to BPH-A.…”

Targeting necroptosis in anticancer therapy: mechanisms and modulators

“…Recently, a series of compounds were reported to be capable of inducing tumor necroptosis in different pathways ( Table 1 ) 95 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 . Several of them have been previously known to act by typical antitumor mechanisms, whose new role in necroptosis aid to draw a comprehensive mechanism diagram of these antitumor agents.…”

“…Bisphenol A (BPA, 58 ) is an endocrine disruptor with estrogenic and obesogenic activity 42 . SH-SY5Y cells (human neuroblastoma cell line) treated with compound 58 underwent apoptosis within 48 h, then necrosis was occurred and increased gradually 129 . When necroptosis inhibitor 2 was added in combination treatment with compound 58 , necroptosis was replaced by apoptosis, indicating that it induced necroptosis 129 .…”