Ruangjaroon Theetat, Chokchaichamnankit Daranee, Srisomsap Chantragan, Svasti Jisnuson, Paricharttanakul N Monique
Environmental Toxicology Program, Chulabhorn Graduate Institute, Bangkok, Thailand.
Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand.
Biochem Biophys Res Commun. 2017 May 6;486(3):652-658. doi: 10.1016/j.bbrc.2017.03.081. Epub 2017 Mar 18.
Fipronil, a phenylpyrazole insecticide, is more selective in its potency towards insects than humans and is thus commonly used. In this study, we demonstrated that exposure to fipronil may pose a human health risk. We observed in vitro the shortening of neurite outgrowths of SH-SY5Y neuroblastoma cells upon treatment with fipronil, even at a non-cytotoxic concentration. Fipronil induced apoptosis involving caspase-6, which is an apoptotic effector highly implicated in neurodegenerative diseases. Moreover, at a concentration that did not induce apoptosis, mitochondrial dysfunction and autophagic vacuole formation were detected. Interestingly using proteomics, we identified vimentin to be dramatically expressed by SH-SY5Y cells as a response to fipronil treatment. Not only did the expression of total vimentin increase, different isoforms were observed, indicating alterations in post-translational modifications. Vimentin was localized at the neurite outgrowth, possibly to repair the damage in cellular structure. However at high concentrations of fipronil, vimentin was found in less defined fibrils, in bridge-like formation, and dense surrounding vacuoles. In all, our results indicate that vimentin plays an important role in fipronil-induced neurotoxicity in SH-SY5Y cells.
氟虫腈是一种苯基吡唑类杀虫剂，对昆虫的毒性比对人类更具选择性，因此被广泛使用。在本研究中，我们证明接触氟虫腈可能对人类健康构成风险。我们在体外观察到，即使在非细胞毒性浓度下，用氟虫腈处理SH-SY5Y神经母细胞瘤细胞后，神经突生长也会缩短。氟虫腈诱导涉及半胱天冬酶-6的细胞凋亡，半胱天冬酶-6是一种与神经退行性疾病高度相关的凋亡效应因子。此外，在未诱导细胞凋亡的浓度下，检测到线粒体功能障碍和自噬空泡形成。有趣的是，通过蛋白质组学，我们发现波形蛋白在SH-SY5Y细胞中作为对氟虫腈处理的反应而显著表达。不仅总波形蛋白的表达增加，还观察到不同的异构体，表明翻译后修饰发生了改变。波形蛋白定位于神经突生长部位，可能是为了修复细胞结构损伤。然而，在高浓度氟虫腈下，波形蛋白存在于不太明确的纤维中，呈桥状形成，并围绕密集的空泡。总之，我们的结果表明波形蛋白在氟虫腈诱导的SH-SY5Y细胞神经毒性中起重要作用。
