The role of p53 in an apoptotic process caused by an oral malodorous compound in periodontal tissues: A review

摘要

Oral malodor is caused by volatile sulfur compounds (VSCs) composed mainly of hydrogen sulfide (H _2S) and methyl mercaptan. In particular, H _2S is an important compound, since it is a major component of physiologic halitosis. The toxicity of VSCs is similar to that of hydrogen cyanide, and is well investigated. The role of VSCs in reducing collagen in human gingival fibroblasts is one of the main sources of their toxicity to human oral tissues. It has been reported recently that H _2S may cause apoptosis in several periodontal tissues. In human gingival fibroblasts, H _2S inhibits not only cytochrome c oxidase activity but also superoxide dismutase activity. The levels of reactive oxygen species are markedly increased, which causes the release of cytochrome c into the cytoplasm, resulting in caspase-9 activation; finally, the executor caspase, caspase-3, is activated. This pathway is commonly observed in cells from all periodontal tissues. Moreover, p53, an apoptotic factor, and phosphorlylated p53, which is the activated form, are increased by H _2S in keratinocyte stem cells and osteoblasts. H _2S also increases the expression of Bax, a primary response gene playing an important role in p53-mediated apoptosis, but maintains a lower expression of Bcl-2, an anti-apoptotic factor, in osteoblasts. It is concluded that the Bax apoptotic pathway and the mitochondrial pathway are activated by H _2S.