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

doi:10.3967/bes2023.132

科研成果详情

题名	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
作者	TANG, Lu Ming 1; MAO, Bai Ping 2; ZHANG, Bing Ru 2; LI, Jing Jing 2; TANG, Yun Bing 3; LI, Hui Tao 2,3; GE, Ren Shan 2,4
发表日期	2023-11
发表期刊	BIOMEDICAL AND ENVIRONMENTAL SCIENCES 影响因子和分区
语种	英语
原始文献类型	Article
关键词	3 beta-hydroxysteroid dehydrogenase 1 Docking analysis Perfluorooctanesulfonic acid Progesterone Structure-activity relationship
其他关键词	PERFLUOROOCTANE SULFONATE ; SERUM ; CHEMICALS ; PFOA
摘要	Objective This study aimed to compare 9 perfluoroalkyl sulfonic acids (PFSA) with carbon chain lengths (C4-C12) to inhibit human placental 3 beta-hydroxysteroid dehydrogenase 1 (3 beta-HSD1), aromatase, and rat 3 beta-HSD4 activities.Methods Human and rat placental 3 beta-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 3 beta-HSD1 structure-dependently in the order: perfluorooctanesulfonic acid (PFOS, half-maximum inhibitory concentration, IC50: 9.03 +/- 4.83 mu mol/L) > perfluorodecanesulfonic acid (PFDS, 42.52 +/- 8.99 mu mol/L) > perfluoroheptanesulfonic acid (PFHpS, 112.6 +/- 29.39 mu mol/L) > perfluorobutanesulfonic acid (PFBS) = perfluoropentanesulfonic acid (PFPS) = perfluorohexanesulfonic acid (PFHxS) = perfluorododecanesulfonic acid (PFDoS) (ineffective at 100 mu mol/L). 6:2FTS (1H, 1H, 2H, 2H-perfluorooctanesulfonic acid) and 8:2FTS (1H, 1H, 2H, 2H-perfluorodecanesulfonic acid) did not inhibit human 3 beta-HSD1. PFOS and PFHpS are mixed inhibitors, whereas PFDS is a competitive inhibitor. Moreover, 1-10 mu mol/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 3 beta-HSD1 in a carbon chain length-dependent manner. All 100 mu mol/L PFSA solutions did not affect rat 3 beta-HSD4 and human placental aromatase activity.Conclusion Carbon chain length determines inhibitory potency of PFSA on human placental 3 beta-HSD1 in a V-shaped transition at PFOS (C8), with inhibitory potency of PFOS > PFDS > PFHpS > PFBS = PFPS = PFHxS = PFDoS = 6:2FTS = 8:2FTS.
出版者	CHINESE CENTER DISEASE CONTROL & PREVENTION
ISSN	0895-3988
EISSN	2214-0190
卷号	36 期号:11 页码:1015-1027
DOI	10.3967/bes2023.132
页数	13
WOS类目	Environmental Sciences ; Public, Environmental & Occupational Health
WOS研究方向	Environmental Sciences & Ecology ; Public, Environmental & Occupational Health
WOS记录号	WOS:001127136000011
收录类别	SCIE ; SCOPUS
在线发表日期	2023-12
URL	查看原文
PubMed ID	38098322
SCOPUSEID	2-s2.0-85179774578
通讯作者地址	[GE, Ren Shan]Department of Anesthesiology,The Second Affiliated Hospital and Yuying Children Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China
Scopus学科分类	Public Health, Environmental and Occupational Health;Health, Toxicology and Mutagenesis
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/209816
专题	第一临床医学院（信息与工程学院）、附属第一医院_急诊医学附属第一医院_麻醉科
通讯作者	GE, Ren Shan
作者单位	1.Department of Emergency Medicine,The Second Affiliated Hospital and Yuying Children Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China; 2.Department of Anesthesiology,The Second Affiliated Hospital and Yuying Children Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China; 3.Department of Obstetrics and Gynecology,The Second Affiliated Hospital and Yuying Children Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China; 4.Key Laboratory of Structural Malformations in Children of Zhejiang Province,Zhejiang,Wenzhou,325000,China
第一作者单位	第一临床医学院（信息与工程学院）、附属第一医院_急诊医学
通讯作者单位	附属第一医院_麻醉科
第一作者的第一单位	第一临床医学院（信息与工程学院）、附属第一医院_急诊医学
推荐引用方式 GB/T 7714	TANG, Lu Ming,MAO, Bai Ping,ZHANG, Bing Ru,et al. 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[J]. BIOMEDICAL AND ENVIRONMENTAL SCIENCES,2023,36(11):1015-1027.
APA	TANG, Lu Ming., MAO, Bai Ping., ZHANG, Bing Ru., LI, Jing Jing., TANG, Yun Bing., ... & GE, Ren Shan. (2023). 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. BIOMEDICAL AND ENVIRONMENTAL SCIENCES, 36(11), 1015-1027.
MLA	TANG, Lu Ming,et al."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".BIOMEDICAL AND ENVIRONMENTAL SCIENCES 36.11(2023):1015-1027.