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Impacts of prothioconazole and prothioconazole-desthio on bile acid and glucolipid metabolism: Upregulation of CYP7A1 expression in HepG2 cells

文献类型: 外文期刊

作者: Hu, Lingyu 2 ; Wang, Xiaofang 2 ; Qian, Mingrong 3 ; Zhang, Hu 1 ; Jin, Yuanxiang 2 ;

作者机构: 1.Zhejiang Acad Agr Sci, Inst Agroprod Safety & Nutr, Zhejiang Prov Key Lab Food Safety, Hangzhou 310021, Peoples R China

2.Zhejiang Univ Technol, Coll Biotechnol & Bioengn, Hangzhou 310032, Peoples R China

3.Zhejiang Shuren Univ, Interdisciplinary Res Acad, Key Lab Pollut Exposure & Hlth Intervent Zhejiang, Hangzhou 310015, Peoples R China

4.Zhejiang Acad Agr Sci, Inst Agroprod Safety & Nutr, 298 Desheng Middle Rd, Hangzhou 310021, Peoples R China

5.Zhejiang Shuren Univ, Interdisciplinary Res Acad, 8 Shuren St, Hangzhou 310015, Peoples R China

6.Zhejiang Univ Technol, Coll Biotechnol & Bioengn, 18 Chaowang Rd, Hangzhou 310014, Peoples R China

关键词: Prothioconazole; Prothioconazole-desthio; HepG2; Bile acid metabolism; Glucolipid metabolism

期刊名称:PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY ( 影响因子:4.7; 五年影响因子:4.7 )

ISSN: 0048-3575

年卷期: 2024 年 198 卷

页码:

收录情况: SCI

摘要: As an efficient triazole fungicide, prothioconazole (PTC) is widely used for the prevention and control of plant fungal pathogens. It was reported that the residues of PTC and prothioconazole-desthio (PTC-d) have been detected in the environment and crops, and the effects of PTC-d may be higher than that of PTC. Currently, PTC and PTC-d have been proven to induce hepatic metabolic disorders. However, their toxic effects on cellular bile acid (BA) and glucolipid metabolism remain unknown. In this study, HepG2 cells were exposed to 1-500 mu M of PTC or PTC-d. High concentrations of PTC and PTC-d were found to induce cytotoxicity; thus, subsequent experimental exposure was conducted at concentrations of 10-50 mu M. The expression levels of CYP7A1 and TG synthesis-related genes and levels of TG and total BA were observed to increase in HepG2 cells. Molecular docking analysis revealed direct interactions between PTC or PTC-d and CYP7A1 protein. To further investigate the underlying mechanisms, PTC and PTC-d were treated to HepG2 cells in which CYP7A1 expression was knocked down using siCYP7A1. It was observed that PTC and PTC-d affected the BA metabolism process and regulated the glycolipid metabolism process by promoting the expression of CYP7A1. In summary, we comprehensively analyzed the effects and mechanisms of PTC and PTC-d on cellular metabolism in HepG2 cells, providing theoretical data for evaluating the safety and potential risks associated with these substances.

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