Necrosis in human neuronal cells exposed to paraquat

J Toxicol Sci. 2018;43(3):193-202. doi: 10.2131/jts.43.193.

Abstract

Paraquat (PQ) is an herbicide that was once used worldwide, but is now prohibited in many nations due to its high toxicity to humans. However, there are still rare cases of the fetal intoxication of PQ, which was purchased prior to the prohibition in Japan. In this study, several cell death pathways, the mitochondrial stress response, and autophagy were examined in SH-SY5Y cells exposed to PQ. The results reveal the decrease of a mitochondrial stress sensitive-BNIP3 (Bcl-2/adenovirus E1B 19-kDa-interacting protein 3) protein, the suppression of autophagic flux, and the lack of apoptosis as well as other regulated forms of necrosis, such as necroptosis and ferroptosis. Taken together, our preliminary survey of cellular responses against PQ shows that, although responses of mitochondria and autophagy are observed, subsequent cell death is necrosis. Mechanism of PQ-induced SH-SY5Y cell death should be complicated and cannot be explained thoroughly by already-known mechanisms.

Keywords: BNIP3; Cell death; Paraquat; SH-SY5Y cells.

MeSH terms

  • Autophagy / drug effects
  • Cell Death
  • Cells, Cultured
  • Herbicides / toxicity*
  • Humans
  • Membrane Proteins / metabolism
  • Mitochondria / drug effects
  • Necrosis
  • Neurons / drug effects*
  • Neurons / pathology*
  • Paraquat / toxicity*
  • Proto-Oncogene Proteins / metabolism

Substances

  • BNIP3 protein, human
  • Herbicides
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Paraquat