Department of Life Sciences and Centre for Neuroscience B.R.A.I.N., University of Trieste, via Fleming 22, 34127, Trieste, Italy.
Department of Pharmacology, UCL School of Pharmacy, 29/39 Brunswick Square, London, WC1N 1AX, United Kingdom.
Sci Rep. 2019 Feb 14;9(1):2014. doi: 10.1038/s41598-019-38591-x.
The so-called amphibole asbestos fibers are enriched with mineral iron ions, able to stimulate ROS production. We recently reported that crocidolite asbestos was able to interact with the cell membranes of Xenopus laevis oocytes, to alter their electrical membrane properties. Here, we found that applied iron ions (Fe) or HO (for ROS generation) mimicked these effects, suggesting that at least one effect of iron-containing asbestos fiber exposure was mediated by ROS production. Furthermore, combined Fe and HO acted synergistically, producing a membrane effect stronger than that induced by these factors alone. Similar to crocidolite, these changes peaked within 30 minutes of incubation and vanished almost completely after 120 min. However, in the presence of cytochalasin D, which inhibits membrane actin repair mechanisms, crocidolite or applied Fe/HO invariably produced oocyte cell death. While the electrophysiological modifications induced by crocidolite suggested a modification of an intrinsic chloride ion channel, the morphological appearance of the treated oocytes also indicated the formation of membrane "pores"; the effects of asbestos exposure may therefore consist of multiple (not necessarily exclusive) underlying mechanisms. In conclusion, using Xenopus oocytes allowed us for the first time, to focus on a specific membrane effect of crocidolite asbestos exposure, which deserves to be tested also on human lung cell lines. Much available evidence suggests that asbestos fibers damage cells through the production of ROS. Our present data confirm that crocidolite fibers can indeed trigger ROS-mediated damaging effects in the oocyte cell membrane, provided iron ions and HO are available for ROS production.
所谓的闪石类石棉纤维富含矿物质铁离子，能够刺激 ROS 的产生。我们最近报道了青石棉石棉能够与非洲爪蟾卵母细胞的细胞膜相互作用，改变其细胞膜的电特性。在这里，我们发现应用的铁离子（Fe）或 HO（用于 ROS 的产生）模拟了这些效应，表明至少一种含铁石棉纤维暴露的效应是通过 ROS 产生介导的。此外，Fe 和 HO 的联合作用具有协同作用，产生的膜效应比这些因素单独作用更强。类似于青石棉，这些变化在孵育 30 分钟内达到峰值，并在 120 分钟后几乎完全消失。然而，在细胞松弛素 D 的存在下，它抑制了膜肌动蛋白修复机制，青石棉或应用的 Fe/HO 总是导致卵母细胞死亡。虽然青石棉引起的电生理学变化表明氯离子通道的内在修饰，但处理后的卵母细胞的形态外观也表明了膜“孔”的形成；因此，石棉暴露的影响可能包括多种（不一定排他）潜在机制。总之，使用非洲爪蟾卵母细胞使我们首次能够关注青石棉暴露的特定膜效应，这值得在人类肺细胞系上进行测试。大量现有证据表明，石棉纤维通过产生 ROS 来破坏细胞。我们目前的数据证实，青石棉纤维确实可以在卵母细胞膜中引发 ROS 介导的损伤效应，只要有铁离子和 HO 用于 ROS 的产生。
