International Journal of Oral Biology

The Korean Academy of Oral Biology (대한구강생물학회)
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Constituents Released from Streptococcus mutans Attenuate Arecoline-mediated Cytotoxicity in HGF Cells by Altering Intracellular $Ca^{2+}$ Signaling

  • Erkhembaatar, Munkhsoyol (Department of Oral Physiology, College of Dentistry, Wonkwang University) ;
  • Oh, Hyuncheol (College of Pharmacy, Wonkwang University) ;
  • Kim, Min Seuk (Department of Oral Physiology, College of Dentistry, Wonkwang University)
  • Received : 2014.02.26
  • Accepted : 2014.03.14
  • Published : 2014.03.31
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Abstract

Streptococcus mutans (S. mutans) is a facultative anaerobic bacterium mainly found in the oral cavity and is known to contribute to tooth decay and gingivitis. Recent studies on intestinal microbiota have revealed that microorganisms forming a biofilm play important roles in maintaining tissue homeostasis through their own metabolism. However, the physiological roles of oral microorganisms such as S. mutans are still unclear. In our current study, we identified that constituents released from S. mutans (CR) reduce arecoline-mediated cytotoxicity without producing toxic effects themselves. Arecoline, as a major alkaloid of areca nut, is known to mediate cytotoxicity on oral epithelial cells and induces a sustained intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$) increase that is cytotoxic. The exposure of human gingival fibroblast (HGF) cells to CR not only inhibited the sustained $[Ca^{2+}]_i$ increase but also the initial $[Ca^{2+}]_i$ elevation. In contrast, CR had no effects on the gene regulation mediated by arecoline. These results demonstrate that S. mutans has physiological role in reducing cytotoxicity in HGF cells and may be considered a novel pharmaceutical candidate.

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References

  1. Loesche WJ. Role of Streptococcus mutans in human dental decay. Microbiol Rev. 1986;50:353-380.
  2. Loesche WJ. Microbiology of Dental Decay and Periodontal Disease. in Medical Microbiology, S. Baron, Editor 1996: Galveston (TX).
  3. Jenkinson HF, Lamont RJ. Oral microbial communities in sickness and in health. Trends Microbiol. 2005;13:589-595. https://doi.org/10.1016/j.tim.2005.09.006
  4. Jakubovics NS, Gill SR, Vickerman MM, Kolenbrander PE. Role of hydrogen peroxide in competition and cooperation between Streptococcus gordonii and Actinomyces naeslundii. FEMS Microbiol Ecol. 2008;66:637-644. https://doi.org/10.1111/j.1574-6941.2008.00585.x
  5. Diaz PI. Microbial diversity and interactions in subgingival biofilm communities. Front Oral Biol. 2012;15:17-40.
  6. Kamada N, Nunez G. Regulation of the Immune System by the Resident Intestinal Bacteria. Gastroenterology in press.
  7. Ramakrishna BS. Role of the gut microbiota in human nutrition and metabolism. J Gastroenterol Hepatol. 2013;28(Suppl. 4):9-17. https://doi.org/10.1111/jgh.12294
  8. Jeng JH, Tsai CL, Hahn LJ, Yang PJ, Kuo YS, Kuo MY. Arecoline cytotoxicity on human oral mucosal fibroblasts related to cellular thiol and esterase activities. Food Chem Toxicol. 1999;37:751-756. https://doi.org/10.1016/S0278-6915(99)00050-2
  9. Jeng JH, Hahn LJ, Lin BR, Hsieh CC, Chan CP, Chang MC. Effects of areca nut, inflorescence piper betle extracts and arecoline on cytotoxicity, total and unscheduled DNA synthesis in cultured gingival keratinocytes. J Oral Pathol Med. 1999;28:64-71.
  10. Chang YC, Hu CC, Lii CK, Tai KW, Yang SH, Chou MY. Cytotoxicity and arecoline mechanisms in human gingival fibroblasts in vitro. Clin Oral Investig. 2001;5:51-56. https://doi.org/10.1007/s007840000085
  11. Jeng JH, Lan WH, Hahn LJ, Hsieh CC, Kuo MY. Inhibition of the migration, attachment, spreading, growth and collagen synthesis of human gingival fibroblasts by arecoline, a major areca alkaloid, in vitro. J Oral Pathol Med. 1996;25:371-75. https://doi.org/10.1111/j.1600-0714.1996.tb00281.x
  12. Yang YR, Chang KC, Chen CL, Chiu TH. Arecoline excites rat locus coeruleus neurons by activating the M2-muscarinic receptor. Chin J Physiol. 2000;43:23-28.
  13. Birnbaumer L. Expansion of signal transduction by G proteins. The second 15 years or so: from 3 to 16 alpha subunits plus betagamma dimers. Biochim Biophys Acta. 2007;1768:772-793. https://doi.org/10.1016/j.bbamem.2006.12.002
  14. Morris AJ, Malbon CC. Physiological regulation of G protein-linked signaling. Physiol Rev. 1999;79:1373-1430. https://doi.org/10.1152/physrev.1999.79.4.1373
  15. Berridge MJ, Bootman MD, Lipp P. Calcium--a life and death signal. Nature 1998;395:645-648. https://doi.org/10.1038/27094
  16. Kim MS, Hong JH, Li Q, Shin DM, Abramowitz J, Birnbaumer L, Muallem S. Deletion of TRPC3 in mice reduces store-operated Ca2+ influx and the severity of acute pancreatitis. Gastroenterology 2009;137:1509-1517. https://doi.org/10.1053/j.gastro.2009.07.042
  17. Xu ZP, Yang K, Xu GN, Zhu L, Hou LN, Zhang WH, Chen HZ, Cui YY. Role of M3 mAChR in in vivo and in vitro models of LPS-induced inflammatory response. Int Immunopharmacol. 2012;14:320-327. https://doi.org/10.1016/j.intimp.2012.07.020
  18. Chiang SL, Jiang SS, Wang YJ, Chiang HC, Chen PH, Tu HP, Ho KY, Tsai YS, Chang IS, Ko YC. Characterization of arecoline-induced effects on cytotoxicity in normal human gingival fibroblasts by global gene expression profiling. Toxicol Sci. 2007;100:66-74. https://doi.org/10.1093/toxsci/kfm201
  19. Berridge MJ, Lipp P, Bootman MD. The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol. 2000;1:11-21. https://doi.org/10.1038/35036035
  20. Thangjam GS, Agarwal P, Balapure AK, Rao SG, Kondaiah P. Regulation of extracellular matrix genes by arecoline in primary gingival fibroblasts requires epithelial factors. J Periodontal Res. 2009;44:736-743. https://doi.org/10.1111/j.1600-0765.2008.01185.x
  21. Wang J, Qi J, Zhao H, He S, Zhang Y, Wei S, Zhao F. Metagenomic sequencing reveals microbiota and its functional potential associated with periodontal disease. Sci Rep. 2013;3:1843. https://doi.org/10.1038/srep01843
  22. Ishii M, Kurachi Y. Muscarinic acetylcholine receptors. Curr Pharm Des. 2006;12:3573-3581. https://doi.org/10.2174/138161206778522056
  23. Khan I, Kumar N, Pant I, Narra S, Kondaiah P. Activation of TGF-beta pathway by areca nut constituents: a possible cause of oral submucous fibrosis. PLoS One 2012;7:e51806. https://doi.org/10.1371/journal.pone.0051806