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合成玻璃体纤维暴露对卵母细胞模型中 TMEM16A 通道的影响。

Effect of Synthetic Vitreous Fiber Exposure on TMEM16A Channels in a Oocyte Model.

机构信息

Department of Life Sciences, University of Trieste, 34127 Trieste, Italy.

CERIC-ERIC, Strada Statale 14, Km 163.5, AREA Science Park, 34149 Trieste, Italy.

出版信息

Int J Mol Sci. 2024 Aug 8;25(16):8661. doi: 10.3390/ijms25168661.

DOI:10.3390/ijms25168661
PMID:39201347
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11354525/
Abstract

Many years ago, asbestos fibers were banned and replaced by synthetic vitreous fibers because of their carcinogenicity. However, the toxicity of the latter fibers is still under debate, especially when it concerns the early fiber interactions with biological cell membranes. Here, we aimed to investigate the effects of a synthetic vitreous fiber named FAV173 on the oocyte membrane, the cell model we have already used to characterize the effect of crocidolite asbestos fiber exposure. Using an electrophysiological approach, we found that, similarly to crocidolite asbestos, FAV173 was able to stimulate a chloride outward current evoked by step membrane depolarizations, that was blocked by the potent and specific TMEM16A channel antagonist Ani9. Exposure to FAV173 fibers also altered the oocyte cell membrane microvilli morphology similarly to crocidolite fibers, most likely as a consequence of the TMEM16A protein interaction with actin. However, FAV173 only partially mimicked the crocidolite fibers effects, even at higher fiber suspension concentrations. As expected, the crocidolite fibers' effect was more similar to that induced by the co-treatment with (Fe + HO), since the iron content of asbestos fibers is known to trigger reactive oxygen species (ROS) production. Taken together, our findings suggest that FAV173 may be less harmful that crocidolite but not ineffective in altering cell membrane properties.

摘要

许多年前,由于石棉纤维的致癌性,它们被合成玻璃纤维取代。然而,后者纤维的毒性仍存在争议,尤其是在涉及早期纤维与生物细胞膜相互作用时。在这里,我们旨在研究一种名为 FAV173 的合成玻璃纤维对卵母细胞膜的影响,我们已经使用该细胞模型来表征青石棉纤维暴露的影响。我们采用电生理学方法发现,与青石棉相似,FAV173 能够刺激由膜去极化引起的氯离子外向电流,该电流被强效且特异的 TMEM16A 通道拮抗剂 Ani9 阻断。暴露于 FAV173 纤维也会改变卵母细胞膜微绒毛的形态,这很可能是 TMEM16A 蛋白与肌动蛋白相互作用的结果。然而,FAV173 仅部分模拟了青石棉纤维的作用,即使在更高的纤维悬浮液浓度下也是如此。正如预期的那样,青石棉纤维的作用更类似于与(Fe + HO)共同处理诱导的作用,因为已知石棉纤维中的铁含量会引发活性氧(ROS)的产生。总之,我们的研究结果表明,FAV173 可能不如青石棉纤维有害,但在改变细胞膜特性方面并非无效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e738/11354525/f3b7686b6de8/ijms-25-08661-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e738/11354525/dfd6eb49ce6f/ijms-25-08661-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e738/11354525/d661a98294c2/ijms-25-08661-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e738/11354525/638ca784ccf6/ijms-25-08661-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e738/11354525/f3b7686b6de8/ijms-25-08661-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e738/11354525/dfd6eb49ce6f/ijms-25-08661-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e738/11354525/d661a98294c2/ijms-25-08661-g002.jpg
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The Xenopus Oocyte: A Tool for Membrane Biology.非洲爪蟾卵母细胞:膜生物学的一种工具。
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2
Asbestos Fibers Enhance the TMEM16A Channel Activity in Xenopus Oocytes.石棉纤维增强非洲爪蟾卵母细胞中的TMEM16A通道活性。
Membranes (Basel). 2023 Feb 1;13(2):180. doi: 10.3390/membranes13020180.
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Systematic review of epidemiological studies evaluating the association between exposure to man-made vitreous fibers and non-malignant respiratory diseases.评估接触人造玻璃纤维与非恶性呼吸道疾病之间关联的流行病学研究的系统评价
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TMEM16A, a Homoharringtonine Receptor, as a Potential Endogenic Target for Lung Cancer Treatment.TMEM16A,一种高三尖杉酯碱受体,作为肺癌治疗的潜在内源性靶点。
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