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

• Published in: International journal of molecular sciences 2023-10, Vol.24 (20), p.15266
• Main Authors: Sule, Rasheed O, Phinney, Brett S, Salemi, Michelle R, Gomes, Aldrin V
• Format: Article
• Language: English
• Subjects: Agriculture; Animals; Antioxidants; B cells; cardiovascular diseases; Cell death; Chromatography, Liquid; Cytotoxicity; Fatty acids; Groundwater; Heart; Herbicides; Herbicides - toxicity; Humans; Investigations; Mass spectrometry; Metabolism; Mice; Mitochondria; Mitochondria - metabolism; Oxidation; Oxidative stress; Pesticides; Physiological aspects; Plants - metabolism; prometryn; Prometryne - analysis; Prometryne - metabolism; Prometryne - pharmacology; Proteasome Endopeptidase Complex; Proteins; Proteolysis; Proteomics; Tandem Mass Spectrometry; Toxicity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms242015266

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.