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三嗪类除草剂扑灭津处理的小鼠心脏中存在线粒体和蛋白酶体功能障碍。

Mitochondrial and Proteasome Dysfunction Occurs in the Hearts of Mice Treated with Triazine Herbicide Prometryn.

机构信息

Department of Neurobiology, Physiology, and Behavior, University of California, Davis, One Shields Ave., Davis, CA 95616, USA.

Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

出版信息

Int J Mol Sci. 2023 Oct 17;24(20):15266. doi: 10.3390/ijms242015266.

DOI:10.3390/ijms242015266
PMID:37894945
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10607192/
Abstract

Prometryn is a methylthio-s-triazine herbicide used to control the growth of annual broadleaf and grass weeds in many cultivated plants. Significant traces of prometryn are documented in the environment, mainly in waters, soil, and plants used for human and domestic consumption. Previous studies have shown that triazine herbicides have carcinogenic potential in humans. However, there is limited information about the effects of prometryn on the cardiac system in the literature, or the mechanisms and signaling pathways underlying any potential cytotoxic effects are not known. It is important to understand the possible effects of exogenous compounds such as prometryn on the heart. To determine the mechanisms and signaling pathways affected by prometryn (185 mg/kg every 48 h for seven days), we performed proteomic profiling of male mice heart with quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) using ten-plex tandem mass tag (TMT) labeling. The data suggest that several major pathways, including energy metabolism, protein degradation, fatty acid metabolism, calcium signaling, and antioxidant defense system were altered in the hearts of prometryn-treated mice. Proteasome and immunoproteasome activity assays and expression levels showed proteasome dysfunction in the hearts of prometryn-treated mice. The results suggest that prometryn induced changes in mitochondrial function and various signaling pathways within the heart, particularly affecting stress-related responses.

摘要

扑灭通是一种用于控制许多栽培植物中一年生阔叶杂草和禾本科杂草生长的甲基硫代三嗪类除草剂。扑灭通在环境中,主要在水中、土壤和供人类和家庭消费的植物中,有大量的痕量存在。先前的研究表明,三嗪类除草剂对人类具有致癌潜力。然而,文献中关于扑灭通对心脏系统的影响的信息有限,也不知道任何潜在细胞毒性作用的机制和信号通路。了解扑灭通等外源性化合物对心脏的可能影响很重要。为了确定扑灭通(每 48 小时 185mg/kg,连续七天)影响的机制和信号通路,我们使用 10 重串联质量标签(TMT)标记的定量液相色谱-串联质谱(LC-MS/MS)对雄性小鼠心脏进行蛋白质组学分析。数据表明,在扑灭通处理的小鼠心脏中,包括能量代谢、蛋白质降解、脂肪酸代谢、钙信号和抗氧化防御系统在内的几个主要途径发生了改变。蛋白酶体和免疫蛋白酶体活性测定和表达水平显示,扑灭通处理的小鼠心脏中的蛋白酶体功能失调。结果表明,扑灭通诱导了心脏中线粒体功能和各种信号通路的变化,特别是影响与应激相关的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/baac/10607192/a2d8192ff48c/ijms-24-15266-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/baac/10607192/a2d8192ff48c/ijms-24-15266-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/baac/10607192/450b32a0981b/ijms-24-15266-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/baac/10607192/e22b5dee738b/ijms-24-15266-g002.jpg
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