Alteration in folate carrier expression via histone deacetylase inhibition in BeWo human placental choriocarcinoma cells

IF 2.6 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro Pub Date : 2024-09-03 DOI:10.1016/j.tiv.2024.105934

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引用次数: 0

Abstract

Folates are essential nutrients for fetal development during pregnancy. Valproic acid (VPA), an inhibitor of histone deacetylases (HDACs), alters the expression of folate carriers in placental cells; however, the underlying mechanisms remain unclear. Here, we aimed to determine the profiles of folate carriers (folate receptor alpha [FOLR1], solute carrier [SLC]-19A1, and SLC46A1) after inhibition of HDACs, especially class I and IIa HDACs, using different inhibitors and gene knockdown tests. Quantitative polymerase chain reaction revealed that BeWo cells (a trophoblast model) expressed HDACs and folate carriers, similar to human placental villi. FOLR1 expression was upregulated by VPA, apicidin, and trichostatin A, but downregulated by MS-275 after 24 h treatment. VPA and apicidin upregulated the expression of SLC46A1. These inhibitors downregulated SLC19A1 expression. TMP269 (a class IIa inhibitor) did not affect folate carrier levels. HDAC1/2 knockdown upregulated FOLR1 and SLC46A1 levels, whereas HDAC1/3 knockdown downregulated FOLR1 levels. Our findings suggest that the pharmacological inhibition of class I HDACs alters the expression of folate carriers in BeWo cells. By contrast, HDAC inhibitors exert different regulatory effects on folate carriers. Moreover, HDAC1/2 inhibition may be a potential mechanism involved in altering FOLR1 and SLC46A1 levels.

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通过抑制组蛋白去乙酰化酶改变 BeWo 人胎盘绒毛膜癌细胞中叶酸载体的表达。

叶酸是孕期胎儿发育所必需的营养素。丙戊酸（VPA）是组蛋白去乙酰化酶（HDACs）的抑制剂，可改变胎盘细胞中叶酸载体的表达；然而，其潜在机制仍不清楚。在此，我们采用不同的抑制剂和基因敲除试验，旨在确定叶酸载体（叶酸受体α [FOLR1]、溶质载体[SLC]-19A1和SLC46A1）在抑制HDACs（尤其是I类和IIa类HDACs）后的表达情况。定量聚合酶链反应显示，BeWo细胞（滋养细胞模型）表达HDACs和叶酸载体，与人类胎盘绒毛相似。经过 24 小时的处理后，VPA、芹菜素和三环锡 A 会上调 FOLR1 的表达，而 MS-275 则会下调 FOLR1 的表达。VPA和芹菜素能上调SLC46A1的表达。这些抑制剂下调了 SLC19A1 的表达。TMP269（一种 IIa 类抑制剂）不影响叶酸载体水平。敲除 HDAC1/2 会上调 FOLR1 和 SLC46A1 的水平，而敲除 HDAC1/3 则会下调 FOLR1 的水平。我们的研究结果表明，药理学抑制 I 类 HDAC 会改变 BeWo 细胞中叶酸载体的表达。相比之下，HDAC抑制剂对叶酸载体的调控作用各不相同。此外，HDAC1/2抑制可能是改变FOLR1和SLC46A1水平的潜在机制。

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

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.