Oral malodorous compound activates mitochondrial pathway inducing apoptosis in human gingival fibroblasts.
Hydrogen sulfide (H(2)S) is a main cause of physiologic halitosis. H(2)S induces apoptosis in human gingival cells, which may play an important role in periodontal pathology. Recently, it has been reported that H(2)S induced apoptosis and DNA damage in human gingival fibroblasts (HGFs) by increasing the levels of reactive oxygen species. However, the mechanisms of H(2)S-induced apoptosis have not been clarified in HGFs. The objective of this study was to determine the apoptotic pathway activated by H(2)S in HGFs. The HGFs were exposed to 50 ng/mL H(2)S, resulting in 18 ng/mL in the culture medium, which is lower than the concentration in periodontal pockets. The number of apoptotic cells after 24 and 48 h incubation was significantly higher than that in the control cultures (p < 0.05). Mitochondrial membrane depolarization and the release of cytochrome c, and caspase-3, and caspase-9 were also significantly increased after both 24- and 48-h incubation (p < 0.05), whereas caspase-8, a key enzyme in the receptor ligand-mediated pathway causing apoptosis, was not activated. The present study shows that H(2)S triggered the mitochondrial pathway causing apoptosis in HGFs but did not activate the receptor ligand-mediated pathway.
Fujimura
Maiko
M
Periodontology, Department of Hard Tissue Engineering, Tokyo Medical and Dental University, Tokyo, Japan.
Calenic
Bogdan
B
Yaegaki
Ken
K
Murata
Takatoshi
T
Ii
Hisataka
H
Imai
Toshio
T
Sato
Tutomu
T
Izumi
Yuichi
Y
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006209:Halitosis / Q000378:metabolism*; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism
D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D006862:Hydrogen Sulfide