6-PPD quinone at environmentally relevant concentrations disrupts citric acid cycle in Caenorhabditis elegans: Role of reduction in acetyl CoA and pyruvate contents
The 6-PPD quinone (6-PPDQ) is derived from 6-PPD, an antioxidant added in tires. Citric acid cycle plays a pivotal role in biochemical metabolisms. In Caenorhabditis elegans, we examined effect of 6-PPDQ exposure on citric acid cycle and the role of alteration in acetyl CoA and pyruvate contents dur...
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KeAi Communications Co., Ltd.
2025-01-01
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| author | Xin Wan Geyu Liang Dayong Wang |
| author_facet | Xin Wan Geyu Liang Dayong Wang |
| author_sort | Xin Wan |
| collection | DOAJ |
| description | The 6-PPD quinone (6-PPDQ) is derived from 6-PPD, an antioxidant added in tires. Citric acid cycle plays a pivotal role in biochemical metabolisms. In Caenorhabditis elegans, we examined effect of 6-PPDQ exposure on citric acid cycle and the role of alteration in acetyl CoA and pyruvate contents during this process. In citric acid cycle, contents of intermediates were reduced by 0.1–10 μg/L 6-PPDQ. Meanwhile, expression of key enzyme genes (cts-1, idh-2, dlst-1, and dld-1) for citric acid cycle was decreased by 0.1–10 μg/L 6-PPDQ. After 6-PPDQ exposure, citric acid content was reduced by cts-1 RNAi, and NADH content was reduced by idh-2, dlst-1, and dld-1 RNAi. Exposure to 6-PPDQ (0.1–10 μg/L) further decreased acetyl CoA and pyruvate contents, and inhibited expression of enzyme genes (dlat-1 and dld-1) governing acetyl CoA synthesis and enzyme genes (pyk-1 and pyk-2) governing pyruvate synthesis. After 6-PPDQ exposure, dlat-1 and dld-1 RNAi reduced contents of acetyl CoA, citric acid, and NADH, and pyk-1 and pyk-2 RNAi reduced contents of pyruvate, citric acid, and NADH. In 6-PPDQ exposed nematodes, cts-1, idh-2, dlst-1, dld-1, dlat-1, pyk-1, and pyk-2 RNAi further caused susceptibility to 6-PPDQ toxicity. Our results suggested 6-PPDQ exposure risk in resulting in damage on citric acid cycle, which was linked to its toxicity induction. |
| format | Article |
| id | doaj-art-bf5a085093f54ed584ac86575d8af749 |
| institution | DOAJ |
| issn | 2590-1826 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | KeAi Communications Co., Ltd. |
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| series | Environmental Chemistry and Ecotoxicology |
| spelling | doaj-art-bf5a085093f54ed584ac86575d8af7492025-08-20T03:18:27ZengKeAi Communications Co., Ltd.Environmental Chemistry and Ecotoxicology2590-18262025-01-0171119112910.1016/j.enceco.2025.05.0226-PPD quinone at environmentally relevant concentrations disrupts citric acid cycle in Caenorhabditis elegans: Role of reduction in acetyl CoA and pyruvate contentsXin Wan0Geyu Liang1Dayong Wang2Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, ChinaKey Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, China; Corresponding authors.Medical School, Southeast University, Nanjing, China; Corresponding authors.The 6-PPD quinone (6-PPDQ) is derived from 6-PPD, an antioxidant added in tires. Citric acid cycle plays a pivotal role in biochemical metabolisms. In Caenorhabditis elegans, we examined effect of 6-PPDQ exposure on citric acid cycle and the role of alteration in acetyl CoA and pyruvate contents during this process. In citric acid cycle, contents of intermediates were reduced by 0.1–10 μg/L 6-PPDQ. Meanwhile, expression of key enzyme genes (cts-1, idh-2, dlst-1, and dld-1) for citric acid cycle was decreased by 0.1–10 μg/L 6-PPDQ. After 6-PPDQ exposure, citric acid content was reduced by cts-1 RNAi, and NADH content was reduced by idh-2, dlst-1, and dld-1 RNAi. Exposure to 6-PPDQ (0.1–10 μg/L) further decreased acetyl CoA and pyruvate contents, and inhibited expression of enzyme genes (dlat-1 and dld-1) governing acetyl CoA synthesis and enzyme genes (pyk-1 and pyk-2) governing pyruvate synthesis. After 6-PPDQ exposure, dlat-1 and dld-1 RNAi reduced contents of acetyl CoA, citric acid, and NADH, and pyk-1 and pyk-2 RNAi reduced contents of pyruvate, citric acid, and NADH. In 6-PPDQ exposed nematodes, cts-1, idh-2, dlst-1, dld-1, dlat-1, pyk-1, and pyk-2 RNAi further caused susceptibility to 6-PPDQ toxicity. Our results suggested 6-PPDQ exposure risk in resulting in damage on citric acid cycle, which was linked to its toxicity induction.http://www.sciencedirect.com/science/article/pii/S25901826250007126-PPDQCitric acid cycleMetabolismC. elegans |
| spellingShingle | Xin Wan Geyu Liang Dayong Wang 6-PPD quinone at environmentally relevant concentrations disrupts citric acid cycle in Caenorhabditis elegans: Role of reduction in acetyl CoA and pyruvate contents Environmental Chemistry and Ecotoxicology 6-PPDQ Citric acid cycle Metabolism C. elegans |
| title | 6-PPD quinone at environmentally relevant concentrations disrupts citric acid cycle in Caenorhabditis elegans: Role of reduction in acetyl CoA and pyruvate contents |
| title_full | 6-PPD quinone at environmentally relevant concentrations disrupts citric acid cycle in Caenorhabditis elegans: Role of reduction in acetyl CoA and pyruvate contents |
| title_fullStr | 6-PPD quinone at environmentally relevant concentrations disrupts citric acid cycle in Caenorhabditis elegans: Role of reduction in acetyl CoA and pyruvate contents |
| title_full_unstemmed | 6-PPD quinone at environmentally relevant concentrations disrupts citric acid cycle in Caenorhabditis elegans: Role of reduction in acetyl CoA and pyruvate contents |
| title_short | 6-PPD quinone at environmentally relevant concentrations disrupts citric acid cycle in Caenorhabditis elegans: Role of reduction in acetyl CoA and pyruvate contents |
| title_sort | 6 ppd quinone at environmentally relevant concentrations disrupts citric acid cycle in caenorhabditis elegans role of reduction in acetyl coa and pyruvate contents |
| topic | 6-PPDQ Citric acid cycle Metabolism C. elegans |
| url | http://www.sciencedirect.com/science/article/pii/S2590182625000712 |
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