Long-Term Exposure to 6-PPD Quinone Inhibits Glutamate Synthesis and Glutamate Receptor Function Associated with Its Toxicity Induction in <i>Caenorhabditis elegans</i>
6-PPD quinone (6-PPDQ) is widely distributed in environments. In <i>Caenorhabditis elegans</i>, we first examined the effects of 6-PPDQ on glutamate synthesis and receptor function by analyzing glutamate content, related gene expression, and phenotypes after RNAi of these genes. Moreover...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
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| Series: | Toxics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2305-6304/13/6/434 |
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| Summary: | 6-PPD quinone (6-PPDQ) is widely distributed in environments. In <i>Caenorhabditis elegans</i>, we first examined the effects of 6-PPDQ on glutamate synthesis and receptor function by analyzing glutamate content, related gene expression, and phenotypes after RNAi of these genes. Moreover, we performed glutamate treatment after 6-PPDQ exposure to determine the potential pharmacological effects of glutamate against 6-PPDQ toxicity. After exposure, the glutamate content was reduced by 0.1–10 μg/L 6-PPDQ, which was due to decreased expression of <i>W07E1.1</i>, <i>glna-1/2/3</i>, and <i>alh-6</i> governing glutamate synthesis from α-ketoglutarate, glutamine, and proline. RNAi of <i>W07E1.1</i>, <i>glna-1/2/3</i>, and <i>alh-6</i> decreased glutamate content in 6-PPDQ-exposed nematodes, and caused susceptibility to 6-PPDQ toxicity. Among glutamate transporter genes, <i>glt-1</i> expression was decreased by 0.1–10 μg/L 6-PPDQ. Moreover, 0.1–10 μg/L 6-PPDQ decreased glutamate receptor genes (<i>glr-1</i>, <i>glr-2</i>, and <i>glr-4</i>), and their expression was decreased by RNAi of <i>W07E1.1</i>, <i>glna-1/2/3</i>, <i>alh-6</i>, and <i>glt-1</i>. RNAi of these receptor genes resulted in susceptibility to 6-PPDQ toxicity, and <i>daf-7</i>, <i>jnk-1</i>, and <i>dbl-1</i> were identified as targets of neuronal <i>glr-1</i>, <i>glr-2</i>, and <i>glr-4</i>. Furthermore, 5 mM glutamate suppressed 6-PPDQ toxicity and increased expression of <i>glr-1</i>, <i>glr-2</i>, and <i>glr-4</i>. Our results demonstrated the risk of 6-PPDQ exposure in disrupting glutamate synthesis and affecting function of glutamate receptors, which was related to 6-PPDQ toxicity induction. |
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| ISSN: | 2305-6304 |