Exposure to 6-PPD Quinone Disrupts Adsorption and Catabolism of Leucine and Causes Mitochondrial Dysfunction in <i>Caenorhabditis elegans</i>
6-PPD quinone (6-PPDQ) is a derivative from 6-PPD, an antioxidant added in tires. Leucine is an important amino acid that needs to be obtained from the diet. In <i>Caenorhabditis elegans</i>, we examined the effect of 6-PPDQ exposure at environmentally relevant concentrations (ERCs) on t...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
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| Series: | Toxics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2305-6304/13/7/544 |
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| Summary: | 6-PPD quinone (6-PPDQ) is a derivative from 6-PPD, an antioxidant added in tires. Leucine is an important amino acid that needs to be obtained from the diet. In <i>Caenorhabditis elegans</i>, we examined the effect of 6-PPDQ exposure at environmentally relevant concentrations (ERCs) on the content of leucine and underlying mechanisms. In nematodes, 0.1–10 μg/L of 6-PPDQ decreased leucine content. The expression of the <i>aat-1</i>-encoding amino acid transmembrane transporter was decreased by 0.1–10 μg/L of 6-PPDQ, and leucine content was reduced by <i>aat-1</i> RNAi. Meanwhile, the expression of <i>bcat-1</i>-encoding branched-chain amino acid transferase was increased by 0.1–10 μg/L of 6-PPDQ, and leucine content was increased by <i>bcat-1</i> RNAi. Additionally, the expressions of <i>dbt-1</i> and <i>ivd-1</i> encoding two enzyme genes governing NADH and FADH<sub>2</sub> generations were decreased by 0.1–10 μg/L of 6-PPDQ, and their expressions in 6-PPDQ exposed nematodes were increased by <i>bcat-1</i> RNAi. After 6-PPDQ exposure, NADH content was reduced by <i>dbt-1</i> RNAi, and FADH<sub>2</sub> content was reduced by <i>ivd-1</i> RNAi. Moreover, 6-PPDQ-induced mitochondrial dysfunction and other aspects of toxicity (such as intestinal ROS generation and lipofuscin accumulation, inhibited locomotion, and reduced brood size) were suppressed by <i>bcat-1</i> RNAi and strengthened by <i>dbt-1</i> and <i>ivd-1</i> RNAi. The 6-PPDQ-induced toxicity and the decrease in <i>dbt-1</i> and <i>ivd-1</i> expressions could be inhibited by following leucine (5 mM) treatment. Our results demonstrate the important association of leucine adsorption and catabolism with 6-PPDQ toxicity induction. |
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| ISSN: | 2305-6304 |