{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T21:06:22Z","timestamp":1773349582943,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Prolonged occupational exposure to oil mist particulate matter (OMPM) poses health risks, yet its neurotoxic effects and underlying mechanisms remain poorly understood. Here, OMPM generated from turbine oil commonly used in occupational labor environments was used to expose rats. The rats were divided into the control and OMPM groups. Following 42 days of exposure, a multidimensional assessment was performed using untargeted metabolomics, phosphoproteomics, behavioral testing, hematoxylin\u2013eosin (HE) staining, transmission electron microscopy (TEM), colorimetric assays, enzyme-linked immunosorbent assay, and Western blotting (WB) to evaluate metabolic alterations, protein phosphorylation, and tissue integrity in the striatum. Integrated omics analyses revealed that differentially phosphorylated proteins and metabolites were remarkably enriched in dopaminergic synapse, Parkinson\u2019s disease, and amphetamine addiction pathways (FDR &lt; 0.05), with a regulatory axis involving L-tyrosine, tyrosine hydroxylase (TH), and dopamine (DA) identified. OMPM-exposed rats exhibited depression- and anxiety-like behaviors, alongside striatal pathological and ultrastructural damage. Biochemical analyses showed elevated malondialdehyde and reactive oxygen species levels; reduced superoxide dismutase, glutathione, and glutathione peroxidase activities and total antioxidant capacity; increased glutathione disulfide and inducible nitric oxide synthase expression; and decreased DA and L-tyrosine levels. Additionally, proinflammatory mediators (IL-1\u03b2, IL-6, TNF-\u03b1, MCP-1, and PGD2) were significantly upregulated in the striatum. WB analysis further confirmed significant reductions in the relative phosphorylation levels of key regulators in dopaminergic and calcium signaling pathways, including CALM3, CaMK2b, GSK-3\u03b2, PRKCG, and TH. Collectively, these findings reveal critical molecular and biochemical alterations in the rat striatum following OMPM exposure and provide a mechanistic basis for understanding depression-like behaviors associated with prolonged OMPM exposure in occupational workers.<\/jats:p>","DOI":"10.3390\/toxics14030249","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:23:03Z","timestamp":1773307383000},"page":"249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protein Modifications and Metabolic Alterations in the Rat Striatum Following Oil Mist Particulate Matter Exposure Revealed via Untargeted Metabolomics and Phosphoproteomics"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6311-3924","authenticated-orcid":false,"given":"Huipeng","family":"Nie","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Shi","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huanliang","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenqing","family":"Lai","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang","family":"Li","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8968-5277","authenticated-orcid":false,"given":"Lei","family":"Tian","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuge","family":"Xi","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7726-9831","authenticated-orcid":false,"given":"Bencheng","family":"Lin","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125340","DOI":"10.1016\/j.envpol.2024.125340","article-title":"Oil mist particulate matter induces myocardial tissue injury by impairing fatty acid metabolism and mitochondrial bioenergetics function via inhibiting the PPAR alpha signaling pathway in rats","volume":"365","author":"Liu","year":"2025","journal-title":"Environ. Pollut."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"113759","DOI":"10.1016\/j.ecoenv.2022.113759","article-title":"Combined multi-omics analysis reveals oil mist particulate matter-induced lung injury in rats: Pathological damage, proteomics, metabolic disturbances, and lung dysbiosis","volume":"241","author":"Nie","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"151119","DOI":"10.1016\/j.scitotenv.2021.151119","article-title":"Adverse pulmonary impacts of environmental concentrations of oil mist particulate matter in normal human bronchial epithelial cell","volume":"809","author":"Lai","year":"2022","journal-title":"Sci. Total Environ."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Nie, H., Liu, H., Shi, Y., Lai, W., Liu, X., Xi, Z., and Lin, B. (2022). Effects of different concentrations of oil mist particulate matter on pulmonary fibrosis in vivo and in vitro. Toxics, 10.","DOI":"10.3390\/toxics10110647"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1097\/00043764-200207000-00013","article-title":"Cancer of the brain and nervous system and occupational exposures in finnish women","volume":"44","author":"Wesseling","year":"2002","journal-title":"J. Occup. Environ. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"108883","DOI":"10.1016\/j.envint.2024.108883","article-title":"Particulate matter induces depression-like behavior through systemic inflammation and brain-derived neurotrophic factors","volume":"194","author":"Li","year":"2024","journal-title":"Environ. Int."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kim, H.J., Kim, J.H., Lee, S., Do, P.A., Lee, J.Y., Cha, S.K., and Lee, J. (2024). Pm2.5 exposure triggers hypothalamic oxidative and er stress leading to depressive-like behaviors in rats. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252413527"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41586-023-06492-9","article-title":"Dopamine and glutamate regulate striatal acetylcholine in decision-making","volume":"621","author":"Chantranupong","year":"2023","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1177\/1073858418824256","article-title":"The striatum\u2019s role in executing rational and irrational economic behaviors","volume":"25","author":"Bamford","year":"2019","journal-title":"Neuroscientist"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.neuron.2019.03.003","article-title":"A motivational and neuropeptidergic hub: Anatomical and functional diversity within the nucleus accumbens shell","volume":"102","author":"Castro","year":"2019","journal-title":"Neuron"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.neubiorev.2020.02.010","article-title":"Do the effects of cannabis on the hippocampus and striatum increase risk for psychosis?","volume":"112","author":"Daniju","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/s41593-024-01819-9","article-title":"Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors","volume":"28","author":"Arenivar","year":"2025","journal-title":"Nat. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"112204","DOI":"10.1016\/j.celrep.2023.112204","article-title":"The dopamine neuron synaptic map in the striatum","volume":"42","author":"Chuhma","year":"2023","journal-title":"Cell Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"521","DOI":"10.3758\/s13415-020-00783-8","article-title":"Baseline-dependent effect of dopamine\u2019s precursor l-tyrosine on working memory gating but not updating","volume":"20","author":"Jongkees","year":"2020","journal-title":"Cogn. Affect. Behav. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3342","DOI":"10.1038\/s41467-024-47456-5","article-title":"Dopamine signaling enriched striatal gene set predicts striatal dopamine synthesis and physiological activity in vivo","volume":"15","author":"Sportelli","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/1478-811X-11-34","article-title":"Complexity of dopamine metabolism","volume":"11","author":"Meiser","year":"2013","journal-title":"Cell Commun. Signal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e70106","DOI":"10.1002\/jimd.70106","article-title":"Consensus guideline for the diagnosis and treatment of tyrosine hydroxylase (th) deficiency","volume":"48","author":"Bondarenko","year":"2025","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s00702-018-1903-3","article-title":"Human tyrosine hydroxylase in parkinson\u2019s disease and in related disorders","volume":"126","author":"Nagatsu","year":"2019","journal-title":"J. Neural Transm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"395","DOI":"10.2174\/187152712800792785","article-title":"A synopsis on the role of tyrosine hydroxylase in parkinson\u2019s disease","volume":"11","author":"Tabrez","year":"2012","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.abb.2010.12.017","article-title":"Tyrosine hydroxylase and regulation of dopamine synthesis","volume":"508","author":"Daubner","year":"2011","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/B978-0-12-411512-5.00002-6","article-title":"Tyrosine hydroxylase: Regulation by feedback inhibition and phosphorylation","volume":"68","author":"Dickson","year":"2013","journal-title":"Adv. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6852","DOI":"10.1038\/s41467-023-42311-5","article-title":"Acetylcholine waves and dopamine release in the striatum","volume":"14","author":"Matityahu","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/bs.apcsb.2019.01.004","article-title":"Dopamine signaling in the striatum","volume":"116","author":"Valjent","year":"2019","journal-title":"Adv. Protein Chem. Struct. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"350","DOI":"10.2174\/187152712800792901","article-title":"Overview of tyrosine hydroxylase in parkinson\u2019s disease","volume":"11","author":"Zhu","year":"2012","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s10571-018-0632-3","article-title":"Dopamine: Functions, signaling, and association with neurological diseases","volume":"39","author":"Klein","year":"2019","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1021\/acssynbio.4c00101","article-title":"Protein interaction kinetics delimit the performance of phosphorylation-driven protein switches","volume":"13","author":"Winter","year":"2024","journal-title":"ACS Synth. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3892\/ijmm.2017.3036","article-title":"The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (review)","volume":"40","author":"Ardito","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e261","DOI":"10.1002\/mco2.261","article-title":"Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications","volume":"4","author":"Zhong","year":"2023","journal-title":"MedComm"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1080\/14789450.2023.2176756","article-title":"Advances in phosphoproteomics and its application to copd","volume":"19","author":"Zeng","year":"2022","journal-title":"Expert Rev. Proteom."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"117066","DOI":"10.1016\/j.trac.2023.117066","article-title":"Mass spectrometry-based phosphoproteomics in clinical applications","volume":"163","author":"Wu","year":"2023","journal-title":"Trends Anal. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9836256","DOI":"10.1155\/2018\/9836256","article-title":"Onco-multi-omics approach: A new frontier in cancer research","volume":"2018","author":"Chakraborty","year":"2018","journal-title":"BioMed Res. Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"119266","DOI":"10.1016\/j.ecoenv.2025.119266","article-title":"Mir-31a-5p targeting crebbp suppresses wnt\/\u03b2-catenin and tgf-\u03b2 pathways to alleviate oil mist particulate matter-induced pulmonary fibrosis","volume":"305","author":"Nie","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1016\/j.molcel.2025.05.007","article-title":"Structural and systems characterization of phosphorylation on metabolic enzymes identifies sex-specific metabolic reprogramming in obesity","volume":"85","author":"Tamir","year":"2025","journal-title":"Mol. Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"123331","DOI":"10.1016\/j.envpol.2024.123331","article-title":"Oil mistparticulate matter exposure induces hyperlipidemia-related inflammation via microbiota\/scfas\/gpr43 axis inhibition and tlr4\/nf-\u03bab activation","volume":"344","author":"Liu","year":"2024","journal-title":"Environ. Pollut."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"a021691","DOI":"10.1101\/cshperspect.a021691","article-title":"The striatum: Where skills and habits meet","volume":"7","author":"Graybiel","year":"2015","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1002\/jnr.24522","article-title":"Compartmental function and modulation of the striatum","volume":"97","author":"Prager","year":"2019","journal-title":"J. Neurosci. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Belosludtseva, N.V., Ilzorkina, A.I., Serov, D.A., Dubinin, M.V., Talanov, E.Y., Karagyaur, M.N., Primak, A.L., Liu, J., and Belosludtsev, K.N. (2024). Ant-mediated inhibition of the permeability transition pore alleviates palmitate-induced mitochondrial dysfunction and lipotoxicity. Biomolecules, 14.","DOI":"10.3390\/biom14091159"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1161\/ATVBAHA.119.312736","article-title":"Diesel exhaust induces mitochondrial dysfunction, hyperlipidemia, and liver steatosis","volume":"39","author":"Yin","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1016\/S0891-5849(03)00150-3","article-title":"Oxidative stress and calcium signaling in the adverse effects of environmental particles (pm10)","volume":"34","author":"Donaldson","year":"2003","journal-title":"Free Radic. Biol. Med."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/14\/3\/249\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T10:32:45Z","timestamp":1773311565000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/14\/3\/249"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,12]]},"references-count":39,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["toxics14030249"],"URL":"https:\/\/doi.org\/10.3390\/toxics14030249","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,12]]}}}