Acetaminophen overdose inhibits steroidogenic acute regulatory protein expression by reducing AKT-mediated SP1 expression in human granulosa-lutein cells

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology Pub Date : 2024-11-29 DOI:10.1016/j.reprotox.2024.108764

Jung-Chien Cheng , Qian Zhang , Lingling Zhang , Beibei Bi , Hailong Wang , Lanlan Fang , Hsun-Ming Chang , Ying-Pu Sun

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Abstract

Overdose of acetaminophen (APAP) has been shown to adversely affect the outcome of pregnancy. The steroidogenic acute regulatory protein (StAR) plays a pivotal role in steroidogenesis, but the impact of APAP on StAR expression in adult human ovarian granulosa cells remains elusive. Here, we demonstrate that APAP overdose leads to the downregulation of StAR expression in the human granulosa cell tumor cell line, KGN, and in the primary culture of human granulosa-lutein (hGL) cells. Treatment of overdose APAP inhibits the activation of the AKT signaling pathway and downregulates the expression of transcription factor SP1. Using a small molecule of AKT activator and SP1 overexpression approaches, we show that the suppressive effect of APAP on StAR expression is mediated through the inhibition of AKT-mediated upregulation of SP1 expression. This study contributes to a deeper understanding of the pharmacological actions of APAP and its impacts on female reproductive health.

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对乙酰氨基酚过量通过降低人颗粒叶黄素细胞中akt介导的SP1表达来抑制类固醇急性调节蛋白的表达。

过量使用对乙酰氨基酚（APAP）已被证明对妊娠结果有不利影响。类固醇急性调节蛋白（steroidogenic acute regulatory protein, StAR）在类固醇形成中起着关键作用，但APAP对成人卵巢颗粒细胞StAR表达的影响尚不清楚。在这里，我们证明了APAP过量导致人颗粒细胞肿瘤细胞系KGN和人颗粒-叶黄素（hGL）细胞原代培养中StAR表达下调。过量APAP治疗可抑制AKT信号通路的激活，下调转录因子SP1的表达。通过小分子AKT激活剂和SP1过表达方法，我们发现APAP对StAR表达的抑制作用是通过抑制AKT介导的SP1表达上调来介导的。本研究有助于深入了解APAP的药理作用及其对女性生殖健康的影响。

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

Reproductive toxicology 生物-毒理学

CiteScore

6.50

自引率

3.00%

发文量

131

审稿时长

45 days

期刊介绍： Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine. All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.