Role of sulfane sulfur species in elemental tellurium nanorod formation in mammalian cells

Yu-ki Tanaka , Hiroki Yanagi , Ayako Shiokawa , Akihiro Matsunaga , Mari Shimura , Satoshi Matsuyama , Yasunori Fukumoto , Noriyuki Suzuki , Yasumitsu Ogra
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Abstract

Tellurium (Te) is an industrially useful element but its oxyanions, such as tellurite and tellurate, are naturally occurring chemical forms that can become a potential source of toxicity to humans and animals. As a means of mitigating the toxicity of Te oxyanions, the formation of less toxic zero-valent elemental Te (Te0) nanostructures has been observed in various species including bacteria, fungi, green algae, and higher plants. In this study, we investigated the formation of Te0 nanorods in human hepatoma HepG2 cells. We detected electron-dense Te nanorods in lysosomes after exposure to potassium tellurite. The amount of Te nanorods in the cells gradually increased with the exposure period. Interestingly, the amount of Te in the insoluble fraction of the culture supernatant was approximately 10 times higher than that in HepG2 cells, suggesting that extracellular reducing agents originating from HepG2 cells transformed tetravalent Te (TeO32−) into Te0 in the culture medium. As an extracellular reducing agent, sulfane sulfur species were considered responsible for the reduction of Te(IV). Then, by inhibiting cystathionine γ-lyase with propargylglycine (PPG), we were able to reduce the amount of sulfane sulfur species generated in the cells. In the presence of PPG, the amount of insoluble Te in the culture supernatant, which was possibly composed of Te0 nanorods, was significantly decreased. The results suggest that sulfane sulfur species are involved in the formation of Te0 nanorods from tellurite in mammalian cells and play a critical role in the amelioration of Te oxyanion toxicity.

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哺乳动物细胞中碲元素纳米棒形成过程中的硫磺物种作用
碲(Te)是一种工业上有用的元素,但它的氧阴离子(如碲化物和碲酸盐)是天然存在的化学形式,可能对人类和动物产生潜在的毒性。为了减轻碲氧阴离子的毒性,在细菌、真菌、绿藻和高等植物等不同物种中观察到了毒性较低的零价元素碲(Te0)纳米结构的形成。在本研究中,我们研究了 Te0 纳米棒在人类肝癌 HepG2 细胞中的形成。暴露于碲化钾后,我们在溶酶体中检测到了电子致密的 Te 纳米棒。细胞中 Te 纳米棒的数量随着暴露时间的延长而逐渐增加。有趣的是,培养上清中不溶部分的 Te 量比 HepG2 细胞中的高出约 10 倍,这表明来自 HepG2 细胞的细胞外还原剂将培养基中的四价 Te(TeO32-)转化成了 Te0。作为一种细胞外还原剂,硫烷硫种被认为是还原 Te(IV)的罪魁祸首。然后,通过使用丙炔甘氨酸(PPG)抑制胱硫醚γ-裂解酶,我们能够减少细胞中产生的烷硫物种的数量。在 PPG 的存在下,培养上清液中的不溶性 Te(可能由 Te0 纳米棒组成)数量显著减少。这些结果表明,烷硫物种参与了哺乳动物细胞中碲形成 Te0 纳米棒的过程,并在改善碲氧阴离子毒性方面发挥了关键作用。
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