FigsharePub Date : 2023-03-13DOI: 10.1021/acs.est.2c08644.s001
Xin Hua (670301), Xiao Feng (106623), Geyu Liang (327126), Jie Chao (582561), Dayong Wang (139014)
{"title":"Exposurento 6‑PPD Quinone at EnvironmentallynRelevant Concentrations Causes Abnormal Locomotion Behaviors and Neurodegenerationnin Caenorhabditis elegans","authors":"Xin Hua (670301), Xiao Feng (106623), Geyu Liang (327126), Jie Chao (582561), Dayong Wang (139014)","doi":"10.1021/acs.est.2c08644.s001","DOIUrl":"https://doi.org/10.1021/acs.est.2c08644.s001","url":null,"abstract":"6-PPDnquinone (6-PPDQ) can be transformed from 6-PPD through ozonation.nNevertheless, the potential neurotoxicity of 6-PPDQ after long-termnexposure and the underlying mechanism are largely unclear. In Caenorhabditis elegans, we here observed that 0.1–10nμg/L of 6-PPDQ caused several forms of abnormal locomotion behaviors.nMeanwhile, the neurodegeneration of D-type motor neurons was observednin 10 μg/L of 6-PPDQ-exposed nematodes. The observed neurodegenerationnwas associated with the activation of the Ca<sup>2+</sup> channelnDEG-3-mediated signaling cascade. In this signaling cascade, expressionsnof <i>deg-3</i>, <i>unc-68</i>, <i>itr-1</i>, <i>crt-1</i>, <i>clp-1</i>, and <i>tra-3</i> were increased by 10 μg/L of 6-PPDQ. Moreover, among genesnencoding neuronal signals required for the control of stress response,nexpressions of <i>jnk-1</i> and <i>dbl-1</i> werendecreased by 0.1–10 μg/L of 6-PPDQ, and expressions of <i>daf-7</i> and <i>glb-10</i> were decreased by 10 μg/Lnof 6-PPDQ. RNAi of <i>jnk-1</i>, <i>dbl-1</i>, <i>daf-7</i>, and <i>glb-10</i> resulted in the susceptibilitynto 6-PPDQ toxicity in decreasing locomotory ability and in inducingnneurodegeneration, suggesting that JNK-1, DBL-1, DAF-7, and GLB-10nwere also required for the induction of 6-PPDQ neurotoxicity. Molecularndocking analysis further demonstrated the binding potential of 6-PPDQnto DEG-3, JNK-1, DBL-1, DAF-7, and GLB-10. Together, our data suggestednthe exposure risk of 6-PPDQ at environmentally relevant concentrationsnin causing neurotoxicity in organisms.","PeriodicalId":522599,"journal":{"name":"Figshare","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147899925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}