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...

Full description

Saved in:
Bibliographic Details
Main Authors: Xin Wan, Geyu Liang, Dayong Wang
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-01-01
Series:Environmental Chemistry and Ecotoxicology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2590182625000712
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849699877459591168
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.
record_format Article
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
work_keys_str_mv AT xinwan 6ppdquinoneatenvironmentallyrelevantconcentrationsdisruptscitricacidcycleincaenorhabditiselegansroleofreductioninacetylcoaandpyruvatecontents
AT geyuliang 6ppdquinoneatenvironmentallyrelevantconcentrationsdisruptscitricacidcycleincaenorhabditiselegansroleofreductioninacetylcoaandpyruvatecontents
AT dayongwang 6ppdquinoneatenvironmentallyrelevantconcentrationsdisruptscitricacidcycleincaenorhabditiselegansroleofreductioninacetylcoaandpyruvatecontents