6-PPD quinone at environmentally relevant concentrations induced damage on longevity in C. elegans: Mechanistic insight from inhibition in mitochondrial UPR response.

Autor: Hua X; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Medical School, Southeast University, Nanjing, China., Wang D; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Medical School, Southeast University, Nanjing, China; Shenzhen Ruipuxun Academy for Stem Cell & Regenerative Medicine, Shenzhen, China. Electronic address: dayongw@seu.edu.cn.
Jazyk: angličtina
Zdroj: The Science of the total environment [Sci Total Environ] 2024 Dec 01; Vol. 954, pp. 176275. Date of Electronic Publication: 2024 Sep 13.
DOI: 10.1016/j.scitotenv.2024.176275
Abstrakt: 6-PPD quinone (6-PPDQ) exists widely in water environment media, causing acute lethality to some aquatic species. Long-term exposure to 6-PPDQ reduced the lifespan of Caenorhabditis elegans. However, the molecular basis for mitochondrial control of 6-PPDQ toxicity remains largely unclear. Using HSP-6 as marker of mitochondrial unfolded protein response (mt UPR), we observed activation of mt UPR by 0.1 and 1 μg/L 6-PPDQ and inhibition in mt UPR by 10 μg/L 6-PPDQ. Additionally, increased atfs-1, ubl-5, and dve-1 expressions were caused by 0.1 and 1 μg/L 6-PPDQ and decreased expressions of these genes were induced by 10 μg/L 6-PPDQ. Neuronal and intestinal RNA interference (RNAi) of hsp-6 caused susceptibility to 6-PPDQ toxicity on longevity, and atfs-1, ubl-5, and dve-1 acted in neurons and intestine to modulate mt UPR and 6-PPDQ toxicity on longevity. Meanwhile, 6-PPDQ (1 and 10 μg/L) increased expressions of histone methyltransferase genes met-2 and set-6, and decreased expressions of histone demethylase genes jmjd-1.2 and jmjd-3.1. Neuronal RNAi of set-6 and intestinal RNAi of met-2 accelerated hsp-6, atfs-1, ubl-5, and dve-1 expressions and extended lifespan of 6-PPDQ exposed nematodes. In contrast, neuronal RNAi of jmjd-1.2 and jmjd-3.1 and intestinal RNAi of jmjd-1.2 suppressed these 4 gene expressions and reduced lifespan of 6-PPDQ exposed nematodes o. In nematodes, RNAi of hsp-6 could also enhance mitochondrial dysfunction and mitochondrial reactive oxygen species (ROS) induced by 6-PPDQ. Therefore, 6-PPDQ caused damage on longevity was associated with suppression in mt UPR, which was under regulation of certain histone methylation related signals.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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