{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T03:21:55Z","timestamp":1785208915045,"version":"3.55.0"},"reference-count":129,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council of Australia","doi-asserted-by":"publisher","award":["APP1070688"],"award-info":[{"award-number":["APP1070688"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council of Australia","doi-asserted-by":"publisher","award":["LP100200680"],"award-info":[{"award-number":["LP100200680"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Australian Research Council","award":["APP1070688"],"award-info":[{"award-number":["APP1070688"]}]},{"name":"Australian Research Council","award":["LP100200680"],"award-info":[{"award-number":["LP100200680"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>The hormonal form of vitamin D3, 1,25(OH)2D3, reduces UV-induced DNA damage. UV exposure initiates pre-vitamin D3 production in the skin, and continued UV exposure photoisomerizes pre-vitamin D3 to produce \u201cover-irradiation products\u201d such as lumisterol3 (L3). Cytochrome P450 side-chain cleavage enzyme (CYP11A1) in skin catalyzes the conversion of L3 to produce three main derivatives: 24-hydroxy-L3 [24(OH)L3], 22-hydroxy-L3 [22(OH)L3], and 20,22-dihydroxy-L3 [20,22(OH)L3]. The current study investigated the photoprotective properties of the major over-irradiation metabolite, 24(OH)L3, in human primary keratinocytes and human skin explants. The results indicated that treatment immediately after UV with either 24(OH)L3 or 1,25(OH)2D3 reduced UV-induced cyclobutane pyrimidine dimers and oxidative DNA damage, with similar concentration response curves in keratinocytes, although in skin explants, 1,25(OH)2D3 was more potent. The reductions in DNA damage by both compounds were, at least in part, the result of increased DNA repair through increased energy availability via increased glycolysis, as well as increased DNA damage recognition proteins in the nucleotide excision repair pathway. Reductions in UV-induced DNA photolesions by either compound occurred in the presence of lower reactive oxygen species. The results indicated that under in vitro and ex vivo conditions, 24(OH)L3 provided photoprotection against UV damage similar to that of 1,25(OH)2D3.<\/jats:p>","DOI":"10.3390\/metabo13070775","type":"journal-article","created":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T02:29:18Z","timestamp":1687400958000},"page":"775","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Over-Irradiation Metabolite Derivative, 24-Hydroxylumister-ol3, Reduces UV-Induced Damage in Skin"],"prefix":"10.3390","volume":"13","author":[{"given":"Warusavithana Gunawardena Manori","family":"De Silva","sequence":"first","affiliation":[{"name":"School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca Yuko","family":"McCarthy","sequence":"additional","affiliation":[{"name":"School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Han","sequence":"additional","affiliation":[{"name":"School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3745-8704","authenticated-orcid":false,"given":"Andrew J. A.","family":"Holland","sequence":"additional","affiliation":[{"name":"Douglas Cohen Department of Paediatric Surgery, The Children\u2019s Hospital at Westmead Clinical School, The Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey","family":"Stern","sequence":"additional","affiliation":[{"name":"Department of Plastic and Constructive Surgery, The Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia"},{"name":"Strathfield Private Hospital, Sydney, NSW 2042, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie Marie","family":"Dixon","sequence":"additional","affiliation":[{"name":"School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6266-6874","authenticated-orcid":false,"given":"Edith Kai Yan","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Molecular Sciences, The University of Western Australia, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5022-4729","authenticated-orcid":false,"given":"Robert Charles","family":"Tuckey","sequence":"additional","affiliation":[{"name":"School of Molecular Sciences, The University of Western Australia, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark Stephen","family":"Rybchyn","sequence":"additional","affiliation":[{"name":"School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1534-9697","authenticated-orcid":false,"given":"Rebecca Sara","family":"Mason","sequence":"additional","affiliation":[{"name":"School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia"},{"name":"School of Life and Environmental Sciences, Charles Perkins Centre, University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1111\/1523-1747.ep12513042","article-title":"Cutaneous Photobiology: Past, Present and Future","volume":"67","author":"Urbach","year":"1976","journal-title":"J. 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