Oxidative stress caused by a low concentration of hydrogen peroxide induces senescence-like changes in
Tamotsu Kiyoshima1, Norio Enoki, Ieyoshi Kobayashi
1Laboratory of Oral Pathology and Medicine, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
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.
Insights
Oxidative stress impacts mouse gingival fibroblasts (MGFs), accelerating aging and causing cell cycle arrest. This premature senescence may link to periodontal disease development.
Area of Science:
- Cell Biology
- Oral Biology
- Aging Research
Background:
- Periodontal tissues degrade due to oxidative stress from oral microflora.
- Cellular aging affects fibroblast function and tissue repair.
- Oxidative stress is a key factor in chronic inflammatory diseases.
Purpose of the Study:
- To investigate the impact of oxidative stress on mouse gingival fibroblasts (MGFs).
- To assess how aging influences MGFs' response to oxidative stress.
- To examine the molecular mechanisms, including p53, p21, and Mdm2, involved in oxidative stress response in MGFs.
Main Methods:
- Cultured MGFs from mice of different ages (10, 30, 52 weeks).
- Exposed MGFs to varying concentrations of hydrogen peroxide (H₂O₂) to induce oxidative stress.
- Analyzed MGF morphology, cell number, cell cycle arrest, and expression of p53, p21, and Mdm2.
Main Results:
- Aging significantly reduced MGF proliferation.
- H₂O₂ induced morphological changes and decreased cell viability at higher concentrations.
- Low H₂O₂ concentrations (20 µM) triggered cell cycle arrest and premature senescence in MGFs, mimicking aged cells.
- Increased phosphorylated p53 and upregulated p21 and Mdm2 mRNA were observed.
Conclusions:
- Oxidative stress, even at low levels, can induce premature senescence in MGFs via cell cycle arrest.
- This stress-induced senescence may contribute to the pathogenesis of periodontal diseases.
- Aging exacerbates the negative effects of oxidative stress on MGFs.
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