DOI QR코드

DOI QR Code

Protein Kinase C-delta Stimulates Haptoglobin Secretion

  • Oh, Mi-Kyung (Department of Natural Sciences, College of Medicine, The Catholic University of Korea) ;
  • Park, Seon-Joo (Department of Natural Sciences, College of Medicine, The Catholic University of Korea) ;
  • Kim, Nam-Hoon (Department of Natural Sciences, College of Medicine, The Catholic University of Korea) ;
  • Kim, In-Sook (Department of Natural Sciences, College of Medicine, The Catholic University of Korea)
  • Published : 2007.01.31

Abstract

Haptoglobin (Hp) is a glycoprotein that is produced by hepatic cells and secreted into the circulation. While studying the physiologic functions of Hp, we found that Hp synthesized in THP-1 monocytic cells was largely retained within cells, although Hp is considered a secretory protein. To investigate the molecular mechanism on Hp secretion in THP-1 cells, in the present study, we examined the effect of protein kinase C (PKC) on Hp secretion. When several inhibitors of PKC isoforms were tested, only Rottlerin, a specific inhibitor of PKC-$\delta$, completely blocked Hp secretion from cells to culture medium. To confirm the role of PKC-$\delta$ in Hp secretion, Hp-overexpressing COS7 cells were transiently transfected with a wild-type or a dominantnegative mutant of the PKC-$\delta$ gene. Mutant PKC-$\delta$ significantly inhibited Hp secretion, whereas the wild-type gene slightly increased Hp secretion. These results demonstrate that the PKC-$\delta$ signal is involved in Hp secretion.

References

  1. Baumann, H. and Gauldie, J. (1994) The acute phase response. Immunol. Today 15, 74-80. https://doi.org/10.1016/0167-5699(94)90137-6
  2. Berkova, N., Gilbert, C., Goupil, S., Yan, J., Korobko, V. and Naccache, P. H. (1999) TNF-induced haptoglobin release from human neutrophils: pivotal role of the TNF p55 receptor. J. Immunol. 162, 6226-6232.
  3. Cid, M. C., Grant, D. S., Hoffman, G. G., Auerbach, R., Fauci, A. S. and Kleinman, H. K. (1993) Identification of haptoglobin as an angiogenic factor in sera from patients with systemic vasculitis. J. Clin. Invest. 91, 977-985. https://doi.org/10.1172/JCI116319
  4. Desilets, A., Gheorghiu, I., Yu, S. J., Seidman, E. G. and Asselin, C. (2000) Inhibition by deacetylase inhibitors of IL-1-dependent induction of haptoglobin involves CCAAT/enhancerbinding protein isoforms in intestinal epithelial cells. Biochem. Biophys. Res. Commun. 276, 673-679. https://doi.org/10.1006/bbrc.2000.3531
  5. Drouin, S. M., Kiley, S. C., Carlino, J. A. and Scott, R. B. (1998) Transforming growth factor-$\beta$2 regulates C3 secretion in monocytes through a protein kinase C-dependent pathway. Mol. Immunol. 35, 1-11. https://doi.org/10.1016/S0161-5890(98)00014-5
  6. Friedrichs, W. E., Navarijo-Ashbaugh, A. L., Bowman, B. H. and Yang, F. (1995) Expression and inflammatory regulation of haptoglobin gene in adipocytes. Biochem. Biophys. Res. Commun. 209, 250-256. https://doi.org/10.1006/bbrc.1995.1496
  7. Goodnight, J. A., Mischak, H., kolch, W. and Mushinski, J. F. (1995) Immunocytochemical localization of eight protein kinase C isozymes overexpressed in NIH 3T3 fibroblasts. J. Biol. Chem. 270, 9991-10001. https://doi.org/10.1074/jbc.270.17.9991
  8. Hanley, J. M., Haugen, T. H. and Heath, E. C. (1983) Biosynthesis and processing of rat haptoglobin. J. Biol. Chem. 258, 7858-7869.
  9. Hanley, J. M. and Heath, E. C. (1985) A novel proteolytic activity in serum processes rat prohaptoglobin. Arch. Biochem. Biophys. 239, 404-419. https://doi.org/10.1016/0003-9861(85)90706-4
  10. Kim, I. S. (1996) Inhibition of hemoglobin-induced low density lipoprotein oxidation by haptoglobin. Exp. Mol. Med. 28, 89-94. https://doi.org/10.1038/emm.1996.14
  11. Kim, I. S., Lee, I. H., Lee, J. H. and Lee, S. Y. (2001) Induction of haptoglobin by all-trans retinoic acid in THP-1 human monocytic cell line. Biochem. Biophys. Res. Commun. 284, 738-742. https://doi.org/10.1006/bbrc.2001.5041
  12. de Klejin, D. P., Smeets, M. B., Kemmeren, P. P., Lim, S. K., Van Middlaar, B. J., Velema, E., Schoneveld, A., Pasterkamp, G. and Borst, C. (2002) Acute-phase protein haptoglobin is a cell migration factor involved in arterial restructuring. FASEB J. 16, 1123-1125. https://doi.org/10.1096/fj.02-0019fje
  13. Lee, I. H., Lee, J. H., Lee, M. J., Lee, S. Y. and Kim, I. S. (2002) Involvement of CCAAT/enhancer-binding protein $\alpha$ in haptoglobin gene expression by all-trans-retinoic acid. Biochem. Biophys. Res. Commun. 294, 956-961. https://doi.org/10.1016/S0006-291X(02)00581-8
  14. Lee, M. Y., Kim, S. Y., Choi, J. S., Lee, I. H., Choi, Y. S., Jin, J. Y., Park, S. J., Sung, K. W., Chun, M. H. and Kim, I. S. (2002) Upregulation of haptoglobin in reactive astrocytes after transient forebrain ischemia in rats. J. Cereb. Blood Flow Metab. 22,1176-1180. https://doi.org/10.1097/01.wcb.0000037989.07114.d1
  15. Lim, Y. K., Jenner, A., Ali, A. B., Wang, Y., Hsu, S. I. H., Chong, S. M., Baumman, H., Halliwell, B. and Lim, S. K. (2000) Haptoglobin reduces renal oxidative DNA and tissue damage during phenylhydrazine-induced hemolysis. Kidney Int. 58, 1033-1044. https://doi.org/10.1046/j.1523-1755.2000.00261.x
  16. Oh, S. K., Pavlotsky, N. and Tauber, A. I. (1990) Specific binding of haptoglobin to human neutrophils and its functional consequences. J. Leukocyte Biol. 47, 142-148. https://doi.org/10.1002/jlb.47.2.142
  17. Soh, J. W., Lee, E. H., Prywes, R. and Weinstein, I. B. (1999) Novel role of specific isoforms of protein kinase C in activation of the c-fos serum response element. Mol. Cell. Biol. 19, 1313-1324. https://doi.org/10.1128/MCB.19.2.1313
  18. Theilgaard-Mönch, K., Jacobsen, L. C., Nielsen, M. J., Rasmussen, T., Udby, L., Gharib, M., Arkwright, P. D., Gombart, A. F., Calafat, J., Moestrup, S. K., Porse, B. T. and Borregaard, N. (2006) Haptoglobin is synthesized during granulocytic differentiation, stored in specific granules, and relesed by neutrophils in response to activation. Blood 108, 353-361. https://doi.org/10.1182/blood-2005-09-3890
  19. Wanger, L., Gessl, A., Parzer, S. B., Base, W., Waldhausl, W. and Pasternack, M. S. (1996) Haptoglobin phenotyping by newly developed monoclonal antibodies. Demonstration of haptoglobin uptake into peripheral blood neutrophils and monocytes. J. Immunol. 156, 989-1996.
  20. Wicher, K. B. and Fries, E. (2004) Prohaptoglobin is proteolytically cleaved in the endoplasmic reticulum by the complement C1rlike protein. Proc. Natl. Acad. Sci. USA 101, 4390-14395. https://doi.org/10.1073/pnas.0400277101
  21. Yang, F., Ghio, A. J., Herbert, D. C., Weaker, F. J., Water, C. A. and Coalson, J. J. (2002) Pulmonary expression of the human haptoglobin gene. Am. J. Respir. Cell Mol. Biol. 23, 277-282.
  22. Yang, F., Haile, D. J., Berger, F. G., Herbert, D. C., Van Beveren, E. and Ghio, A. J. (2003) Haptoglobin reduces lung injury associated with exposure to blood. Am. J. Physiol. Lung Cell Mol. Physiol. 284, 402-409. https://doi.org/10.1152/ajplung.00115.2002

Cited by

  1. Proteomic Analysis of Serum in Lung Cancer Induced by 3-Methylcholanthrene vol.2009, 2009, https://doi.org/10.1155/2009/397910
  2. PKD2 interacts with Lck and regulates NFAT activity in T cells vol.42, pp.1, 2009, https://doi.org/10.5483/BMBRep.2009.42.1.035
  3. The opposite correlation between calcium ion and cyclic-AMP regarding the activation of microsomal triglyceride transfer protein in rat liver vol.42, pp.10, 2009, https://doi.org/10.5483/BMBRep.2009.42.10.642