title: Oxidative stress caused by a low concentration of hydrogen peroxide             induces senescence-like changes in mouse gingival fibroblasts.
abstract: Periodontal tissue deteriorates under persistent oxidative stress induced by inflammatory reactions in the microflora of the oral cavity. This study aimed to evaluate the cellular properties of mouse gingival fibroblasts (MGFs) in the presence of oxidative stress. MGFs from 10-, 30- and 52-week-old mice were used to evaluate the changes in the cellular properties with aging. The study investigated the effects of oxidative stress on the cellular properties of MGFs from 10-week-old mice. The expression of p53, p21 and murine double minute 2 (Mdm2) in the MGFs in response to oxidative stress was also examined. By day 8, the number of MGFs increased in culture. However, the increase was markedly lower in MGFs derived from aged mice. Oxidative stress due to hydrogen peroxide (H2O2)-induced morphological changes characterized by a round shape with enlarged nuclei and expanded cytoplasm. The cell number of MGFs was decreased subsequent to treatment with 50 µM or a higher concentration of H₂O₂. MGFs treated with H₂O₂ at 20 µM showed a similar cell growth curve as the one seen in 52-week-old mice. Phosphorylated p53 protein was increased in MGFs subsequent to treatment with 20 µM H2O2, along with an upregulated transcription of p21 and Mdm2 mRNAs. These results suggest that treatment with a lower concentration of H₂O₂ in MGFs induces cell cycle arrest, resulting in stress-induced premature senescence, possibly correlated with the development of periodontal diseases.
authors.affiliation: Laboratory of Oral Pathology and Medicine, Faculty of Dental                     Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kiyoshima
authors.forename: Norio
authors.initials: N
authors.lastname: Enoki
authors.forename: Ieyoshi
authors.initials: I
authors.lastname: Kobayashi
authors.forename: Takako
authors.initials: T
authors.lastname: Sakai
authors.forename: Kengo
authors.initials: K
authors.lastname: Nagata
authors.forename: Hiroko
authors.initials: H
authors.lastname: Wada
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ookuma
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Sakai
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D048430:Cell Shape; D002470:Cell Survival; D002478:Cells, Cultured; D016922:Cellular Senescence; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression; D005881:Gingiva / Q000166:cytology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016877:Oxidants; D016159:Tumor Suppressor Protein p53; D006861:Hydrogen Peroxide; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2; D001616:beta-Galactosidase