{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:48:39Z","timestamp":1790711319854,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,10,3]],"date-time":"2012-10-03T00:00:00Z","timestamp":1349222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Japanese Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"crossref","award":["2009-1"],"award-info":[{"award-number":["2009-1"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Nippon Dental University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>Hydrogen sulfide (<jats:styled-content style=\"fixed-case\">\n<jats:roman>H<jats:sub>2<\/jats:sub>S<\/jats:roman>\n<\/jats:styled-content>) is a volatile sulfur compound responsible for physiological halitosis. <jats:styled-content style=\"fixed-case\">\n<jats:roman>H<jats:sub>2<\/jats:sub>S<\/jats:roman>\n<\/jats:styled-content> was also reported as having periodontal pathologic activities. Gingival crevicular epithelium is the first barrier against periodontal pathogens and their products; oral keratinocyte stem cells <jats:styled-content style=\"fixed-case\">OKSC<\/jats:styled-content>s play key roles in maintaining this barrier. The p53 pathway is responsible for regulating key biological events. Increased apoptosis and cell\u2010cycle arrest of <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> repair can affect keratinocyte stem cells, having a direct impact on the architecture of the oral epithelial tissue. However, the link between <jats:styled-content style=\"fixed-case\">\n<jats:roman>H<jats:sub>2<\/jats:sub>S<\/jats:roman>\n<\/jats:styled-content>, p53 activity and <jats:styled-content style=\"fixed-case\">OKSC<\/jats:styled-content>s has not yet been fully explored. The main objective of the present study was to explore the implications of the p53 pathway in <jats:styled-content style=\"fixed-case\">OKSC<\/jats:styled-content>s following exposure to <jats:styled-content style=\"fixed-case\">\n<jats:roman>H<jats:sub>2<\/jats:sub>S<\/jats:roman>\n<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>OKSCs were isolated from human gingival epithelium and incubated with physiological levels of <jats:styled-content style=\"fixed-case\">\n<jats:roman>H<jats:sub>2<\/jats:sub>S<\/jats:roman>\n<\/jats:styled-content> for 24 and 48\u00a0h. Apoptosis and the mitochondrial membrane potential were detected using flow cytometry. Cytochrome <jats:italic>c<\/jats:italic>, total p53, phosphorylated p53 and caspase activity were assessed using specific <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>s. p53 Pathway gene activity was assayed using quantitative <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The levels of apoptosis were significantly increased following incubation in the presence of H<jats:sub>2<\/jats:sub>S, especially after 48\u00a0h (36.95\u00a0\u00b1\u00a01.91% vs. 4.77\u00a0\u00b1\u00a00.74%). Caspases 9 and 3 were activated, whereas caspase\u20108 activity remained low. Total p53 activity and particularly phosphorylated p53 at serine 46, were significantly enhanced compared with controls (47.11\u00a0\u00b1\u00a09.84\u00a0units\/mL vs. 1.5\u00a0\u00b1\u00a00\u00a0units\/mL and 32.22\u00a0\u00b1\u00a010.23\u00a0units\/mL\u00a0 vs. 0.15\u00a0\u00b1\u00a00\u00a0units\/mL, respectively, at 48\u00a0h). Among p53 pathway genes, apoptosis\u2010related genes [i.e. phosphatase and tensin homolog (<jats:italic>\n<jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content>\n<\/jats:italic>), B\u2010cell CLL\/lymphoma 2 (<jats:italic>\n<jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>2<\/jats:italic>), sirtuin 3 (<jats:italic>\n<jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>3<\/jats:italic>) and caspases]) were dramatically increased when compared with controls. Moreover, cell\u2010cycle progression genes [i.e. E2F transcription factor (<jats:italic>E2F<\/jats:italic>) family and histone deacetylase (<jats:italic>\n<jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>\n<\/jats:italic>)] and <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010repair genes [i.e. growth arrest and DNA\u2010damage\u2010inducible, gamma (<jats:italic>\n<jats:styled-content style=\"fixed-case\">GADD<\/jats:styled-content>45<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>\n<\/jats:italic>) family and serine\/threonine\u2010protein kinase Chk2 (<jats:italic>\n<jats:styled-content style=\"fixed-case\">CHEK<\/jats:styled-content>2<\/jats:italic>)] were also increased.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Following incubation with <jats:styled-content style=\"fixed-case\">\n<jats:roman>H<jats:sub>2<\/jats:sub>S<\/jats:roman>\n<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> OKSC<\/jats:styled-content>s express multiple p53\u2010associated genes, including programmed cell death, cell\u2010cycle control and <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010repair genes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12011","type":"journal-article","created":{"date-parts":[[2012,10,3]],"date-time":"2012-10-03T09:43:15Z","timestamp":1349257395000},"page":"322-330","source":"Crossref","is-referenced-by-count":34,"title":["p53\u2010Pathway activity and apoptosis in hydrogen sulfide\u2010exposed stem cells separated from human gingival epithelium"],"prefix":"10.1111","volume":"48","author":[{"given":"B.","family":"Calenic","sequence":"first","affiliation":[{"name":"Department of Oral Health Nippon Dental University  Tokyo Japan"},{"name":"Department of Biochemistry Faculty of Dental Medicine University of Medicine and Pharmacy \u201cCarol Davila\u201d  Bucharest 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