Document Detail


Oral malodorous compound causes oxidative stress and p53-mediated programmed cell death in keratinocyte stem cells.
MedLine Citation:
PMID:  20476886     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: It is well known that hydrogen sulfide (H(2)S), the main substance causing physiologic halitosis, is also involved in the etiology of periodontitis. Gingival crevicular epithelium is the first barrier against periodontal pathogens and their products; keratinocyte stem cells play key roles in maintaining this barrier. An increased apoptotic process can affect keratinocyte stem cells, having a direct impact on oral epithelial tissue architecture. Our objective is to determine whether H(2)S induces apoptosis in human keratinocyte stem cells.
METHODS: Apoptosis levels; p53 activity; reactive oxygen species; mitochondrial membrane depolarization; cytochrome C release; and caspase-9, -8, and -3 were assessed using enzyme-linked immunosorbent assay and flow cytometry. Genomic DNA damage was examined using single-cell gel electrophoresis. Real-time polymerase chain reaction was used for Bax detection.
RESULTS: The percentage of apoptotic cells was significantly increased (20.5% +/- 1.6% versus 4.5% +/- 1.1% at 24 hours and 37.8% +/- 5.4% versus 4.8% +/- 0.9% at 48 hours; P <0.05, respectively; n = 5). Mitochondrial membrane potential was collapsed and reactive oxygen species levels were significantly increased compared to their control groups. At each time point the amount of released cytochrome C into the cytosol was significantly increased. Caspase-9 and -3 activities were significantly increased (P <0.05), whereas caspase-8 remained inactive. After both 24 and 48 hours, total and phosphorylated p53 levels were significantly increased.
CONCLUSION: We conclude that H(2)S can induce apoptosis in human keratinocyte stem cells, a key component of the epithelial barrier, following DNA damage and p53 activation.
Authors:
Bogdan Calenic; Ken Yaegaki; Ana Kozhuharova; Toshio Imai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of periodontology     Volume:  81     ISSN:  1943-3670     ISO Abbreviation:  J. Periodontol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-03     Completed Date:  2010-12-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8000345     Medline TA:  J Periodontol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1317-23     Citation Subset:  D; IM    
Affiliation:
Department of Oral Health, Nippon Dental University, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adult Stem Cells / drug effects*
Apoptosis / drug effects*,  physiology
Caspases / analysis,  metabolism
Cells, Cultured
Comet Assay
Cytochromes c / analysis,  metabolism
DNA Damage
Gingiva / cytology,  drug effects*
Humans
Hydrogen Sulfide / pharmacology*
Keratinocytes / drug effects*
Membrane Potential, Mitochondrial / drug effects
Oxidative Stress
Reactive Oxygen Species / metabolism
Tumor Suppressor Protein p53 / analysis,  metabolism
bcl-2-Associated X Protein / analysis,  metabolism
Chemical
Reg. No./Substance:
0/Reactive Oxygen Species; 0/Tumor Suppressor Protein p53; 0/bcl-2-Associated X Protein; 7783-06-4/Hydrogen Sulfide; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspases

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