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Chlorothalonil induces the intestinal epithelial barrier dysfunction in Caco-2 cell-based in vitro monolayer model by activating MAPK pathway.
Tao, Huaping; Bao, Zhiwei; Fu, Zhengwei; Jin, Yuanxiang.
Afiliação
  • Tao H; College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.
  • Bao Z; Institute of Life Sciences, Key Laboratory of Organ Development and Regeneration of Zhejiang Province, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, China.
  • Fu Z; College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.
  • Jin Y; College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.
Acta Biochim Biophys Sin (Shanghai) ; 53(11): 1459-1468, 2021 Nov 10.
Article em En | MEDLINE | ID: mdl-34549778
ABSTRACT
The widespread use of chlorothalonil (CTL) has caused environmental residues and food contamination. Although the intestinal epithelial barrier (IEB) is directly involved in the metabolism and transportation of various exogenous compounds, there are few studies on the toxic effects of these compounds on the structure and function of IEB. The disassembly of tight junction (TJ) is a major cause of intestinal barrier dysfunction under exogenous compounds intake, but the precise mechanisms are not well understood. Here, we used Caco-2 cell monolayers as an in vitro model of human IEB to evaluate the toxicity of CTL exposure on the structure and function of IEB. Results showed that CTL exposure increased the paracellular permeability of the monolayers and downregulated mRNA levels of the TJ genes (ZO-1, OCLN, and CLDN1), polarity marker gene (SI), and anti-apoptosis gene (BCL-2) but upregulated the mRNA levels of apoptosis-related genes, including BAD, BAX, CASP3, and CASP8. Western blot analysis and immunofluorescence assay results showed the decreased levels and disrupted distribution of TJ protein network, including ZO-1 and CLDN1 in CTL-exposed IEB. In addition, the accumulation of intracellular reactive oxygen species, decreased mitochondrial membrane potential, and increased active CASP3 expression were observed in treated IEB. The result of TUNEL assay further confirmed the occurrence of cell apoptosis after CTL exposure. In addition, the phosphorylation of mitogen-activated protein kinases, including ERK, JNK and p38, was increased in CTL-exposed IEB. In summary, our results demonstrated that CTL exposure induced IEB dysfunction in Caco-2 cell monolayers by activating the mitogen-activated protein kinase pathway.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Junções Íntimas / Sistema de Sinalização das MAP Quinases / MAP Quinases Reguladas por Sinal Extracelular / Fungicidas Industriais / Mucosa Intestinal / Nitrilas Idioma: En Revista: Acta Biochim Biophys Sin (Shanghai) Assunto da revista: BIOFISICA / BIOQUIMICA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Junções Íntimas / Sistema de Sinalização das MAP Quinases / MAP Quinases Reguladas por Sinal Extracelular / Fungicidas Industriais / Mucosa Intestinal / Nitrilas Idioma: En Revista: Acta Biochim Biophys Sin (Shanghai) Assunto da revista: BIOFISICA / BIOQUIMICA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China