{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T17:58:15Z","timestamp":1777658295909,"version":"3.51.4"},"reference-count":82,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T00:00:00Z","timestamp":1711584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY016058"],"award-info":[{"award-number":["R01EY016058"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30EY04068"],"award-info":[{"award-number":["P30EY04068"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY035231"],"award-info":[{"award-number":["R01EY035231"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Ophthalmology, Visual and Anatomical Sciences and Kresge Eye Institute","award":["R01EY016058"],"award-info":[{"award-number":["R01EY016058"]}]},{"name":"Department of Ophthalmology, Visual and Anatomical Sciences and Kresge Eye Institute","award":["P30EY04068"],"award-info":[{"award-number":["P30EY04068"]}]},{"name":"Department of Ophthalmology, Visual and Anatomical Sciences and Kresge Eye Institute","award":["R01EY035231"],"award-info":[{"award-number":["R01EY035231"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We have previously shown that PM10 exposure causes oxidative stress and reduces Nrf2 protein levels, and SKQ1 pre-treatment protects against this damage in human corneal epithelial cells (HCE-2). The current study focuses on uncovering the mechanisms underlying acute PM10 toxicity and SKQ1-mediated protection. HCE-2 were pre-treated with SKQ1 and then exposed to 100 \u03bcg\/mL PM10. Cell viability, oxidative stress markers, programmed cell death, DNA damage, senescence markers, and pro-inflammatory cytokines were analyzed. Nrf2 cellular location and its transcriptional activity were determined. Effects of the Nrf2 inhibitor ML385 were similarly evaluated. Data showed that PM10 decreased cell viability, Nrf2 transcriptional activity, and mRNA levels of antioxidant enzymes, but increased p-PI3K, p-NF\u03baB, COX-2, and iNOS proteins levels. Additionally, PM10 exposure significantly increased DNA damage, phosphor-p53, p16 and p21 protein levels, and \u03b2-galactosidase (\u03b2-gal) staining, which confirmed the senescence. SKQ1 pre-treatment reversed these effects. ML385 lowered the Nrf2 protein levels and mRNA levels of its downstream targets. ML385 also abrogated the protective effects of SKQ1 against PM10 toxicity by preventing the restoration of cell viability and reduced oxidative stress. In conclusion, PM10 induces inflammation, reduces Nrf2 transcriptional activity, and causes DNA damage, leading to a senescence-like phenotype, which is prevented by SKQ1.<\/jats:p>","DOI":"10.3390\/ijms25073754","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T12:22:46Z","timestamp":1711628566000},"page":"3754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Mechanisms of PM10 Disruption of the Nrf2 Pathway in Cornea"],"prefix":"10.3390","volume":"25","author":[{"given":"Mallika","family":"Somayajulu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farooq S.","family":"Muhammed","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2084-5441","authenticated-orcid":false,"given":"Robert","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon A.","family":"McClellan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1530-3242","authenticated-orcid":false,"given":"Linda D.","family":"Hazlett","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,28]]},"reference":[{"key":"ref_1","first-page":"8","article-title":"Particulate Matter Is a Surprisingly Common Contributor to Disease","volume":"16","author":"Crinnion","year":"2017","journal-title":"Integr. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3389\/fpubh.2020.00014","article-title":"Environmental and Health Impacts of Air Pollution: A Review","volume":"8","author":"Manisalidis","year":"2020","journal-title":"Front. 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