Chronic exposure to the tire-wear contaminant 6-PPDQ induces senescence-associated biomarkers and neurobehavioral deficits: Involvement of ABL1-p53-autophagy signaling
4 affiliations
- 1School of Basic Medical Sciences, Xinjiang Second Medical College, Karamay, China
- 2College of Life Sciences, Nanjing Agricultural University, China
- 3School of Basic Medical Sciences, Xinjiang Second Medical College, Karamay, China; School of Pharmacy, Xinjiang Second Medical College, Karamay, China; Corresponding author at: School of Pharmacy, Xinjiang Second Medical College, Karamay, China.
- 4Peking University Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing, China; Corresponding author.
Abstract
While 6-PPD quinone (6-PPDQ) is known for its acute lethality to salmonids, its chronic impacts on non-target species remain elusive. Here, we evaluated the chronic toxicity of 6-PPDQ across multiple biological models. Our results demonstrate that 6-PPDQ exposure significantly curtailed the survival and physiological motility of the nematode Caenorhabditis elegans, while inducing cellular senescence-associated biomarkers and a secretory phenotype (SASP) in human MRC-5 cells. In adult zebrafish, chronic exposure over a 28-month follow-up window precipitated cognitive and neurobehavioral deficits, characterized by impaired spatial learning, elevated agonistic reactivity, and glutamatergic excitotoxicity. Through computational screening, molecular docking, and pharmacological rescue, we identified ABL1 as a prioritized candidate target and functional mediator of 6-PPDQ toxicity. Total ABL1 protein abundance was elevated in exposed zebrafish brains alongside p53 accumulation and autophagic substrate (p62 and LC3-II) retention. Importantly, concurrent treatment with the ABL1 kinase inhibitor nilotinib attenuated p53 induction, restored autophagic flux, and rescued locomotor deficits, implicating the ABL1-associated pathway in these phenotypes. Because overt organismal morbidity was manifest predominantly at upper-bound exposure concentrations (10 µg/L), these phenotypes reflect chronic toxic stress rather than an acceleration of natural aging. These findings identify an ABL1-associated mechanism of chronic neurotoxicity and emphasize the need to assess long-term neurological risks associated with tire-wear pollution.
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BibTeX
@article{ma2026chronic,
title = {{Chronic exposure to the tire-wear contaminant 6-PPDQ induces senescence-associated biomarkers and neurobehavioral deficits: Involvement of ABL1-p53-autophagy signaling}},
author = {Zejiang Ma and Manxue Bai and Chunmei Xia and Jianguang Li and Jian Lu},
journal = {Ecotoxicology and Environmental Safety},
year = {2026},
month = oct,
doi = {10.1016/j.ecoenv.2026.120962},
url = {https://doi.org/10.1016/j.ecoenv.2026.120962},
note = {CC BY},
}
RIS
TY - JOUR
TI - Chronic exposure to the tire-wear contaminant 6-PPDQ induces senescence-associated biomarkers and neurobehavioral deficits: Involvement of ABL1-p53-autophagy signaling
AU - Zejiang Ma
AU - Manxue Bai
AU - Chunmei Xia
AU - Jianguang Li
AU - Jian Lu
PY - 2026
DA - 2026/10/24
JO - Ecotoxicology and Environmental Safety
DO - 10.1016/j.ecoenv.2026.120962
UR - https://doi.org/10.1016/j.ecoenv.2026.120962
AB - While 6-PPD quinone (6-PPDQ) is known for its acute lethality to salmonids, its chronic impacts on non-target species remain elusive. Here, we evaluated the chronic toxicity of 6-PPDQ across multiple biological models. Our results demonstrate that 6-PPDQ exposure significantly curtailed the survival and physiological motility of the nematode Caenorhabditis elegans, while inducing cellular senescence-associated biomarkers and a secretory phenotype (SASP) in human MRC-5 cells. In adult zebrafish, chronic exposure over a 28-month follow-up window precipitated cognitive and neurobehavioral deficits, characterized by impaired spatial learning, elevated agonistic reactivity, and glutamatergic excitotoxicity. Through computational screening, molecular docking, and pharmacological rescue, we identified ABL1 as a prioritized candidate target and functional mediator of 6-PPDQ toxicity. Total ABL1 protein abundance was elevated in exposed zebrafish brains alongside p53 accumulation and autophagic substrate (p62 and LC3-II) retention. Importantly, concurrent treatment with the ABL1 kinase inhibitor nilotinib attenuated p53 induction, restored autophagic flux, and rescued locomotor deficits, implicating the ABL1-associated pathway in these phenotypes. Because overt organismal morbidity was manifest predominantly at upper-bound exposure concentrations (10 µg/L), these phenotypes reflect chronic toxic stress rather than an acceleration of natural aging. These findings identify an ABL1-associated mechanism of chronic neurotoxicity and emphasize the need to assess long-term neurological risks associated with tire-wear pollution.
SN - 0147-6513
SN - 1090-2414
ER -