Carbon Chain Length Determines Inhibitory Potency of Perfluoroalkyl Sulfonic Acids on Human Placental 3β-Hydroxysteroid Dehydrogenase 1: Screening, Structure-Activity Relationship, and In Silico Analysis

IF 3 3区 医学 Q2 ENVIRONMENTAL SCIENCES
Lu Ming TANG , Bai Ping MAO , Bing Ru ZHANG , Jing Jing LI , Yun Bing TANG , Hui Tao LI , Ren Shan GE
{"title":"Carbon Chain Length Determines Inhibitory Potency of Perfluoroalkyl Sulfonic Acids on Human Placental 3β-Hydroxysteroid Dehydrogenase 1: Screening, Structure-Activity Relationship, and In Silico Analysis","authors":"Lu Ming TANG ,&nbsp;Bai Ping MAO ,&nbsp;Bing Ru ZHANG ,&nbsp;Jing Jing LI ,&nbsp;Yun Bing TANG ,&nbsp;Hui Tao LI ,&nbsp;Ren Shan GE","doi":"10.3967/bes2023.132","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>This study aimed to compare 9 perfluoroalkyl sulfonic acids (PFSA) with carbon chain lengths (C4-C12) to inhibit human placental 3β-hydroxysteroid dehydrogenase 1 (3β-HSD1), aromatase, and rat 3β-HSD4 activities.</p></div><div><h3>Methods</h3><p>Human and rat placental 3β-HSDs activities were determined by converting pregnenolone to progesterone and progesterone secretion in JEG-3 cells was determined using HPLC/MS–MS, and human aromatase activity was determined by radioimmunoassay.</p></div><div><h3>Results</h3><p>PFSA inhibited human 3β-HSD1 structure-dependently in the order: perfluorooctanesulfonic acid (PFOS, half-maximum inhibitory concentration, IC<sub>50</sub>: 9.03 ± 4.83 µmol/L) &gt; perfluorodecanesulfonic acid (PFDS, 42.52 ± 8.99 µmol/L) &gt; perfluoroheptanesulfonic acid (PFHpS, 112.6 ± 29.39 µmol/L) &gt; perfluorobutanesulfonic acid (PFBS) = perfluoropentanesulfonic acid (PFPS) = perfluorohexanesulfonic acid (PFHxS) = perfluorododecanesulfonic acid (PFDoS) (ineffective at 100 µmol/L). 6:2FTS (1H, 1H, 2H, 2H-perfluorooctanesulfonic acid) and 8:2FTS (1H, 1H, 2H, 2H-perfluorodecanesulfonic acid) did not inhibit human 3β-HSD1. PFOS and PFHpS are mixed inhibitors, whereas PFDS is a competitive inhibitor. Moreover, 1–10 µmol/L PFOS and PFDS significantly reduced progesterone biosynthesis in JEG-3 cells. Docking analysis revealed that PFSA binds to the steroid-binding site of human 3β-HSD1 in a carbon chain length-dependent manner. All 100 µmol/L PFSA solutions did not affect rat 3β-HSD4 and human placental aromatase activity.</p></div><div><h3>Conclusions</h3><p>Carbon chain length determines inhibitory potency of PFSA on human placental 3β-HSD1 in a V-shaped transition at PFOS (C8), with inhibitory potency of PFOS &gt; PFDS &gt; PFHpS &gt; PFBS = PFPS = PFHxS = PFDoS = 6:2FTS = 8:2FTS.</p></div>","PeriodicalId":55364,"journal":{"name":"Biomedical and Environmental Sciences","volume":"36 11","pages":"Pages 1015-1027"},"PeriodicalIF":3.0000,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0895398823001654/pdf?md5=b5ab5012386bac1ba426c1c3ad215137&pid=1-s2.0-S0895398823001654-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedical and Environmental Sciences","FirstCategoryId":"1089","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0895398823001654","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
引用次数: 0

Abstract

Objective

This study aimed to compare 9 perfluoroalkyl sulfonic acids (PFSA) with carbon chain lengths (C4-C12) to inhibit human placental 3β-hydroxysteroid dehydrogenase 1 (3β-HSD1), aromatase, and rat 3β-HSD4 activities.

Methods

Human and rat placental 3β-HSDs activities were determined by converting pregnenolone to progesterone and progesterone secretion in JEG-3 cells was determined using HPLC/MS–MS, and human aromatase activity was determined by radioimmunoassay.

Results

PFSA inhibited human 3β-HSD1 structure-dependently in the order: perfluorooctanesulfonic acid (PFOS, half-maximum inhibitory concentration, IC50: 9.03 ± 4.83 µmol/L) > perfluorodecanesulfonic acid (PFDS, 42.52 ± 8.99 µmol/L) > perfluoroheptanesulfonic acid (PFHpS, 112.6 ± 29.39 µmol/L) > perfluorobutanesulfonic acid (PFBS) = perfluoropentanesulfonic acid (PFPS) = perfluorohexanesulfonic acid (PFHxS) = perfluorododecanesulfonic acid (PFDoS) (ineffective at 100 µmol/L). 6:2FTS (1H, 1H, 2H, 2H-perfluorooctanesulfonic acid) and 8:2FTS (1H, 1H, 2H, 2H-perfluorodecanesulfonic acid) did not inhibit human 3β-HSD1. PFOS and PFHpS are mixed inhibitors, whereas PFDS is a competitive inhibitor. Moreover, 1–10 µmol/L PFOS and PFDS significantly reduced progesterone biosynthesis in JEG-3 cells. Docking analysis revealed that PFSA binds to the steroid-binding site of human 3β-HSD1 in a carbon chain length-dependent manner. All 100 µmol/L PFSA solutions did not affect rat 3β-HSD4 and human placental aromatase activity.

Conclusions

Carbon chain length determines inhibitory potency of PFSA on human placental 3β-HSD1 in a V-shaped transition at PFOS (C8), with inhibitory potency of PFOS > PFDS > PFHpS > PFBS = PFPS = PFHxS = PFDoS = 6:2FTS = 8:2FTS.

碳链长度决定全氟烷基磺酸对人类胎盘 3β- 羟类固醇脱氢酶 1 的抑制效力:筛选、结构-活性关系和硅学分析。
研究目的本研究旨在比较碳链长度为 C4-C12 的 9 种全氟烷基磺酸 (PFSA) 对人胎盘 3β- 羟类固醇脱氢酶 1 (3β-HSD1)、芳香化酶和大鼠 3β-HSD4 活性的抑制作用。方法:通过将孕烯醇酮转化为孕酮测定人和大鼠胎盘 3β-HSDs 的活性,使用 HPLC/MS-MS 测定 JEG-3 细胞中孕酮的分泌量,使用放射免疫测定人芳香化酶的活性:结果:全氟辛烷磺酸对人 3β-HSD1 结构的抑制依次为:全氟辛烷磺酸(PFOS,半最大抑制浓度,IC 50:9.03 ± 4.83 μmol/L) > 全氟癸烷磺酸(PFDS,42.52 ± 8.99 μmol/L) > 全氟庚烷磺酸 (PFHpS, 112.6 ± 29.39 μmol/L) > 全氟丁烷磺酸 (PFBS) = 全氟戊烷磺酸 (PFPS) = 全氟己烷磺酸 (PFHxS) = 全氟十二烷磺酸 (PFDoS) (100 μmol/L 时无效)。6:2FTS(1H、1H、2H、2H-全氟辛烷磺酸)和 8:2FTS(1H、1H、2H、2H-全氟癸烷磺酸)对人类 3β-HSD1 没有抑制作用。PFOS 和 PFHpS 是混合抑制剂,而 PFDS 是竞争抑制剂。此外,1-10 μmol/L PFOS 和 PFDS 能显著降低 JEG-3 细胞中孕酮的生物合成。对接分析表明,全氟辛烷磺酸与人 3β-HSD1 的类固醇结合位点结合的方式与碳链长度有关。所有 100 μmol/L 的 PFSA 溶液都不会影响大鼠 3β-HSD4 和人胎盘芳香化酶的活性:碳链长度决定了 PFSA 对人胎盘 3β-HSD1 的抑制效力,在 PFOS(C8)处呈 V 型转变,抑制效力为 PFOS > PFDS > PFHpS > PFBS = PFPS = PFHxS = PFDoS = 6:2FTS = 8:2FTS。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Biomedical and Environmental Sciences
Biomedical and Environmental Sciences 环境科学-公共卫生、环境卫生与职业卫生
CiteScore
2.60
自引率
8.60%
发文量
2170
审稿时长
1.0 months
期刊介绍: Biomedical and Environmental Sciences (BES) is a peer-reviewed journal jointly established by the Chinese Center for Disease Control and Prevention (China CDC) and the Coulston International Corporation (CIC), USA in 1988, and is published monthly by Elsevier. It is indexed by SCI, PubMed, and CA. Topics covered by BES include infectious disease prevention, chronic and non-communicable disease prevention, disease control based on preventive medicine, and public health theories. It also focuses on the health impacts of environmental factors in people''s daily lives and work, including air quality, occupational hazards, and radiation hazards. Article types considered for publication include original articles, letters to the editor, reviews, research highlights, and policy forum.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信