Triclosan affects steroidogenesis in mouse primary astrocytes in vitro with engagement of Sirtuin 1 and 3

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
Konrad A. Szychowski , Bartosz Skóra
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Abstract

Triclosan (TCS) is a widely used antimicrobial, antifungal, and antiviral agent. To date, it has been reported that TCS can enter the human body and disrupt hormonal homeostasis. Therefore, the aim of our paper was to evaluate the impact of TCS on astrocytes, i.e. a crucial population of cells responsible for steroid hormone production. Our data showed that, in mouse primary astrocyte cultures, TCS can act as an endocrine disrupting chemical through destabilization of the production or secretion of progesterone (P4), testosterone (T), and estradiol (E2). TCS affects the mRNA expression of enzymes involved in neurosteroidogenesis, such as Cyp17a1, 17β-Hsd, and Cyp19a1. Our data showed that a partial PPARγ agonist (honokiol) prevented changes in Cyp17a1 mRNA expression caused by TCS. Similarly, honokiol inhibited TCS-stimulated P4 release. However, rosiglitazone (classic PPARγ agonist) or GW9662 (PPARγ antagonist) had a much stronger effect. Therefore, we believe that the changes observed in the P4, T, and E2 levels are a result of dysregulation of the activity of the aforementioned enzymes, whose expression can be affected by TCS through a Pparγ-dependent pathway. TCS was found to decrease the aryl hydrocarbon receptor (AhR) and Sirtuin 3 protein levels, which may be the result of the activation of the these proteins. Since our study showed dysregulation of the production or secretion of neurosteroids in astrocytes, it can be concluded that TCS reaching the brain may contribute to the development of neurodegenerative diseases in which an abnormal amount of neurosteroids is observed.

三氯生通过参与 Sirtuin 1 和 3 影响体外小鼠原发性星形胶质细胞的类固醇生成。
三氯生(TCS)是一种广泛使用的抗菌剂、抗真菌剂和抗病毒剂。迄今为止,已有报道称三氯生可进入人体并破坏荷尔蒙平衡。因此,我们的论文旨在评估三氯氢硅对星形胶质细胞(即负责类固醇激素分泌的重要细胞群)的影响。我们的数据显示,在小鼠原代星形胶质细胞培养物中,三氯氢硅可通过破坏孕酮(P4)、睾酮(T)和雌二醇(E2)的产生或分泌的稳定性,起到干扰内分泌的化学物质的作用。TCS会影响参与神经类固醇生成的酶的mRNA表达,如Cyp17a1、17β-Hsd和Cyp19a1。我们的数据显示,PPARγ部分激动剂(honokiol)可阻止TCS引起的Cyp17a1 mRNA表达变化。同样,honokiol 也抑制了 TCS 刺激的 P4 释放。然而,罗格列酮(典型的 PPARγ 激动剂)或 GW9662(PPARγ 拮抗剂)的作用更强。因此,我们认为在 P4、T 和 E2 水平上观察到的变化是上述酶活性失调的结果,而 TCS 可通过 Pparγ 依赖性途径影响这些酶的表达。研究发现,TCS 可降低芳基烃受体(AhR)和 Sirtuin 3 蛋白水平,这可能是这些蛋白被激活的结果。由于我们的研究显示星形胶质细胞中神经类固醇的产生或分泌失调,因此可以得出结论,三氯生化碳酸盐进入大脑可能会导致神经类固醇含量异常的神经退行性疾病的发生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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