Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Effects of Phorbol Estr, Gö-6976, Ro-31-8220 and Röttlerin on Basal Mucin Release from Airway Goblet Cells

  • Heo, Ho-Jin (Department of Pharmacology, College of Medicine, Chungnam National University) ;
  • Lee, Hyun-Jae (Department of Pharmacology, College of Medicine, Chungnam National University) ;
  • Seok, Jeong-Ho (Department of Pharmacology, College of Medicine, Chungnam National University) ;
  • Seo, Un-Kyo (Department of Oriental Medicine, College of Oriental Medicine, Dongguk University) ;
  • Lee, Choong-Jae (Department of Pharmacology, College of Medicine, Chungnam National University)
  • Published : 2005.12.01
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Abstract

In the present study, we tried to investigate whether protein kinase C (PKC) activator, phorbol 12-Myristate 13-Acetate (PMA), and PKC inhibitors, $G\"{o}-6976$, Ro-31-8220 and rottlerin significantly affect basal mucin relesed from cultured airway goblet cells. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled with $^3H$-glucosamine for 24 hr and chased for 30 min in the presence of each agent to assess the effects on $^3H$-mucin release. The results were as follows: (1) PMA increased mucin release from cultured HTSE cells, during 30 min of treatment period; (2) However, $G\"{o}-6976$, Ro-31-8220 and rottlerin did not significantly affect mucin release, during 30 min of treatment period. This finding suggests, at least in part, that PKC might playa minor role in the signaling pathways involved in basal - physiological or constitutive - mucin release from airway goblet cells, although further studies are needed.

Keywords

References

  1. Ellis, E. F. (1985). Asthma in childhood. J. Allergy Clin. Immunol. 72 (suppl), 526-539
  2. Gray, T., Nettesheim, P., Basbaum, C, and Koo, J. (2001). Regulation of mucin gene expression in human tracheobronchial epithelial cells by thyroid hormone. Biochem. J. 353, 727-734 https://doi.org/10.1042/0264-6021:3530727
  3. Hewson, C. A., Edbrooke, M. R., and Johnston, S. L. (2004) PMA induces the MUC5AC respiratory mucin in human bronchial epithelial cells, via PKC, EGF/TGF-alpha, Ras/Raf, MEK, ERK and Sp 1-dependent mechanisms. J. Mol. BioI. 344(3), 683-695 https://doi.org/10.1016/j.jmb.2004.09.059
  4. Kim, K. C, McCracken, K., Lee, B. C, Shin, C. Y., Jo, M. -J., Lee, C. J. and Ko, K. H. (1997). Airway goblet cell mucin: its structure and regulation of secretion. Eur. Respir. J. 11, 26442649
  5. Kim, K. C, Rearick, J. I., Nettesheim, P., and Jetten, A. M. (1985). Biochemical characterization of mucous glycoproteins synthesized and secreted by hamster tracheal epithelial cells in primary culture. J. Biol. Chem. 260, 4021-4027
  6. Kim, K. C, Wasano, K., Niles, R. M., Schuster, J. E., Stone, P. J. and Brody, J.S. (1987). Human neutrophil elastase releases cell surface mucins from primary cultures of hamster tracheal epithelial cells. Proc. Natl. Acad. Sci. USA. 84, 9304-9308
  7. Ko, K.H., Jo, M., McCracken, K., and Kim, K.C (1997). ATPinduced mucin release from cultured airway goblet cells involves, in part, activation of protein kinase C. Am. J. Respir. Cell Mol. Biol. 16(2), 194-198 https://doi.org/10.1165/ajrcmb.16.2.9032127
  8. Ko, K.H., Lee, C.J., Shin, C.Y, Jo, M.-J. and Kim, K.C. (1999). Inhibition of mucin release from airway goblet cells by polycationic peptides. Am. J. Physiol. 277(21), L811-L815
  9. Lee, C.J., Paik, S.H., Ko, K.H., Kim, K.C. (2002). Effects of polycationic peptides on mucin release from airway goblet cells: relationship between polymer size and activity. Inflamm. Res. 51(10), 490-494 https://doi.org/10.1007/PL00012417
  10. Martiny-Baron, G., Kazanietz, M.G, Mischak, H., Blumberg, P.M., Kochs, G., Hug, R., Marme, D., and Schachtele, C. (1993). Selective inhibition of protein kinase C isozymes by the indolocarbazole Go-6976. J. Biol. Chem. 268(13), 9194-9197
  11. Shin, C.Y., Jo, M.J., Lee, W.J., Ryu, J.R, Kim, K.C., and Ko, K.H. (2001). ATP-induced mucin release from cultured airway goblet cell involves, in part, activation of phospholipase A2. Methods Find. Exp. Clin. Pharmacol. 23(2), 73-77
  12. Takeyama, K., Dabbagh, K., Lee, H., Agusti, C., Lausier, J.A., Ueki, I.F, Grattan, K.M. and Nadel, J.A. (1999). Epidermal growth factor system regulates mucin production in airways. Proc. Natl. Acad. Sci. USA 6, 3081-3086
  13. Villalba, M., Kasibhatla, S., Genestier, L., Mahboubi, A., Green, D.R., and Altman, A. (1999). Protein kinase c theta cooperates with calcineurin to induce Fas ligand expression during activation-induced T cell death. J. Immunol. 163(11),5813-5819
  14. Wasano, K., Kim, K.C, Niles, R.M., and Brody, J.S. (1988). Membrane differentiation markers of airway epithelial secretory cells. J. Histochem. Cytochem. 36, 167-178 https://doi.org/10.1177/36.2.3335774