دورية أكاديمية

Perfluorooctanesulfonic acid exposure leads to downregulation of 3-hydroxy-3-methylglutaryl-CoA synthase 2 expression and upregulation of markers associated with intestinal carcinogenesis in mouse intestinal tissues.

التفاصيل البيبلوغرافية
العنوان: Perfluorooctanesulfonic acid exposure leads to downregulation of 3-hydroxy-3-methylglutaryl-CoA synthase 2 expression and upregulation of markers associated with intestinal carcinogenesis in mouse intestinal tissues.
المؤلفون: Tessmann JW; Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536, USA. Electronic address: jotessmann@uky.edu., Deng P; College of Pharmaceutical Sciences, Soochow University, Suzhou, China. Electronic address: pandeng@suda.edu.cn., Durham J; Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536, USA. Electronic address: jerika.durham@uky.edu., Li C; Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA. Electronic address: chang.li@uky.edu., Banerjee M; Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA. Electronic address: moumita.banerjee@uky.edu., Wang Q; Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA. Electronic address: qingding.wang@uky.edu., Goettl RA; Markey Cancer Center Biostatistics and Bioinformatics Shared Resource Facility, University of Kentucky, Lexington, KY 40536, USA. Electronic address: ryan.goettl@uky.edu., He D; Markey Cancer Center Biostatistics and Bioinformatics Shared Resource Facility, University of Kentucky, Lexington, KY 40536, USA. Electronic address: dhe2@uky.edu., Wang C; Markey Cancer Center Biostatistics and Bioinformatics Shared Resource Facility, University of Kentucky, Lexington, KY 40536, USA. Electronic address: chi.wang@uky.edu., Lee EY; Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, KY 40536, USA. Electronic address: eylee@uky.edu., Evers BM; Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA. Electronic address: mark.evers@uky.edu., Hennig B; Department of Animal and Food Sciences, University of Kentucky, Lexington, KY 40536, USA. Electronic address: bhennig@uky.edu., Zaytseva YY; Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536, USA; Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA. Electronic address: yyzayt2@uky.edu.
المصدر: Chemosphere [Chemosphere] 2024 Jul; Vol. 359, pp. 142332. Date of Electronic Publication: 2024 May 14.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 0320657 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-1298 (Electronic) Linking ISSN: 00456535 NLM ISO Abbreviation: Chemosphere Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford : Elsevier Science Ltd
Original Publication: Oxford, New York, : Pergamon Press.
مواضيع طبية MeSH: Alkanesulfonic Acids*/toxicity , Fluorocarbons*/toxicity , Hydroxymethylglutaryl-CoA Synthase*/metabolism , Hydroxymethylglutaryl-CoA Synthase*/genetics , Mice, Inbred C57BL* , Carcinogenesis* , Down-Regulation*/drug effects, Animals ; Mice ; Intestinal Neoplasms/chemically induced ; Intestinal Neoplasms/metabolism ; Intestinal Neoplasms/pathology ; Up-Regulation/drug effects ; Environmental Pollutants/toxicity ; Intestines/drug effects ; Humans ; Intestinal Mucosa/metabolism
مستخلص: Perfluorooctanesulfonic acid (PFOS) is a widely recognized environment pollutant known for its high bioaccumulation potential and a long elimination half-life. Several studies have shown that PFOS can alter multiple biological pathways and negatively affect human health. Considering the direct exposure to the gastrointestinal (GI) tract to environmental pollutants, PFOS can potentially disrupt intestinal homeostasis. However, there is limited knowledge about the effect of PFOS exposure on normal intestinal tissues, and its contribution to GI-associated diseases remains to be determined. In this study, we examined the effect of PFOS exposure on the gene expression profile of intestinal tissues of C57BL/6 mice using RNAseq analysis. We found that PFOS exposure in drinking water significantly downregulates mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting ketogenic enzyme, in intestinal tissues of mice. We found that diets containing the soluble fibers inulin and pectin, which are known to be protective against PFOS exposure, were ineffective in reversing the downregulation of HMGCS2 expression in vivo. Analysis of intestinal tissues also demonstrated that PFOS exposure leads to upregulation of proteins implicated in colorectal carcinogenesis, including β-catenin, c-MYC, mTOR and FASN. Consistent with the in vivo results, PFOS exposure leads to downregulation of HMGCS2 in mouse and human normal intestinal organoids in vitro. Furthermore, we show that shRNA-mediated knockdown of HMGCS2 in a human normal intestinal cell line resulted in increased cell proliferation and upregulation of key proliferation-associated proteins such as cyclin D, survivin, ERK1/2 and AKT, along with an increase in lipid accumulation. In summary, our results suggest that PFOS exposure may contribute to pathological changes in normal intestinal cells via downregulation of HMGCS2 expression and upregulation of pro-carcinogenic signaling pathways that may increase the risk of colorectal cancer development.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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معلومات مُعتمدة: P30 CA177558 United States CA NCI NIH HHS; P42 ES007380 United States ES NIEHS NIH HHS; R01 CA249734 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Colorectal carcinogenesis; Environmental pollutants; Gastrointestinal tract; HMGCS2; Ketogenesis; Perfluorooctanesulfonic acid
المشرفين على المادة: 0 (Alkanesulfonic Acids)
9H2MAI21CL (perfluorooctane sulfonic acid)
0 (Fluorocarbons)
EC 2.3.3.10 (Hydroxymethylglutaryl-CoA Synthase)
EC 2.3.3.10 (HMGCS2 protein, mouse)
0 (Environmental Pollutants)
تواريخ الأحداث: Date Created: 20240516 Date Completed: 20240604 Latest Revision: 20240612
رمز التحديث: 20240612
مُعرف محوري في PubMed: PMC11157449
DOI: 10.1016/j.chemosphere.2024.142332
PMID: 38754493
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-1298
DOI:10.1016/j.chemosphere.2024.142332