Hirayama Naho, Aki Toshihiko, Funakoshi Takeshi, Noritake Kanako, Unuma Kana, Uemura Koichi
J Toxicol Sci. 2018;43(3):193-202. doi: 10.2131/jts.43.193.
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.
百草枯（PQ）是一种曾在全球范围内使用的除草剂，但由于其对人类具有高毒性，现在许多国家已禁止使用。然而，仍有罕见的PQ胎儿中毒病例，这些病例中的PQ是在日本禁止使用之前购买的。在本研究中，我们检测了暴露于PQ的SH-SY5Y细胞中的几种细胞死亡途径、线粒体应激反应和自噬。结果显示，线粒体应激敏感蛋白BNIP3（Bcl-2/腺病毒E1B 19 kDa相互作用蛋白3）减少，自噬流受到抑制，且不存在凋亡以及其他形式的程序性坏死，如坏死性凋亡和铁死亡。综上所述，我们对细胞对PQ反应的初步研究表明，虽然观察到了线粒体和自噬的反应，但随后的细胞死亡是坏死。PQ诱导SH-SY5Y细胞死亡的机制应该很复杂，无法用已知机制完全解释。
