Ecotoxicology and Environmental Safety (2021-04-01)

The orphan nuclear receptor Nur77 plays a vital role in BPA-induced PC12 cell apoptosis

  • Yingchun Zhang,
  • Shuang Li,
  • Jin Wu,
  • Yuan Peng,
  • Jialei Bai,
  • Baoan Ning,
  • Xinxing Wang,
  • Yanjun Fang,
  • Dianpeng Han,
  • Shuyue Ren,
  • Sen Li,
  • Ruipeng Chen,
  • Kang Li,
  • Hongwei Du,
  • Zhixian Gao

Journal volume & issue
Vol. 213
p. 112026

Abstract

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Bisphenol A (BPA) is a typical environmental endocrine disruptor that can migrate into organisms through skin contact, breathing, diet and various other approaches. The reproductive toxicity and neurotoxicity of BPA has been confirmed by several toxicological studies. However, the neurotoxicity of BPA is still controversial. In the present study, we used PC12 cells as a model to investigate the mechanism of BPA-induced neuronal apoptosis. BPA exposure reduced cell viability, altered cell morphology and aggravated intracellular Lactate dehydrogenase (LDH) release, intracellular Ca2+ concentration, Reactive oxygen species (ROS) levels, apoptosis and the reduction in the mitochondrial transmembrane potential (ΔΨm). Moreover, the results of the Western blot (WB) and Real-time quantitative polymerase chain reaction (RT-qPCR) assays indicated that the expression levels of Nur77 in the BPA group were down-regulated and accompanied by the downregulation of the NF-κb/Bcl-2 proteins and the upregulation of cleaved-caspase 3, which is a marker of apoptosis. However, these changes were significantly reversed with the upregulation of the Nur77 protein by introducing plasmids carrying the nur77 gene. These results indicated that BPA-induced apoptosis was closely related to Nur77-mediated inhibition of the NF-κb/Bcl-2 pathway.

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