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Gene Review

Mcpt1  -  mast cell protease 1

Rattus norvegicus

Synonyms: CLIP protein, Chymase, Chymotrypsin-like protease, Mast cell protease 1, Mast cell protease I, ...
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Disease relevance of Mcpt1


High impact information on Mcpt1


Biological context of Mcpt1


Anatomical context of Mcpt1

  • We now describe the cloning of a full-length cDNA encoding a novel chymase from rat vascular smooth muscle cells [1].
  • This chymase was induced in hypertrophied rat pulmonary arteries, with 11-fold and 8-fold higher chymase mRNA levels in aortic and pulmonary artery smooth muscle cells from spontaneously hypertensive than in corresponding tissues from normotensive rats [1].
  • Angiotensin II-forming chymase is expressed in the pulmonary arteries of the monocrotaline-induced pulmonary hypertensive rats, but its actual role is unclear [10].
  • Based on the sequence of RMCP1 or RMCP2 cDNAs, selective oligoprobes were designed and their specificity established by Northern blot analysis of mRNAs purified from tongue and jejunum, two tissues containing selectively type 1 and 2 protease, respectively [11].
  • Chymase activity in the non-infarcted myocardium was significantly increased in the vehicle group, but it was significantly reduced by chymase inhibitor treatment [2].

Associations of Mcpt1 with chemical compounds

  • While greater than 80% of angiotensin II (Ang II) formation in the human heart and greater than 60% in arteries appears to result from chymase activity, no cardiovascular cell-expressed chymase has been previously reported [1].
  • CONCLUSIONS: We have demonstrated selective overexpression of human chymase gene in the heart of transgenic mice, and the results support the hypothesis of a dual Ang II-forming pathway from chymase and ACE in the cardiac tissue in vivo [8].
  • In this study we found that remnant chymase, by proteolyzing human serum and human aortic intimal fluid, prevents these two physiologic fluids from effectively inducing cholesterol efflux from cultured macrophage foam cells [12].
  • RESULTS: Intracisternal injection of the TRH analogue RX 77368 (30 ng) induced a transient increase in intestinal release of RMCP II and PGD2 that was abolished by dox-antrazole [13].
  • However, both systemic capsaicin and indo-methacin enhanced RMCP II release [13].

Enzymatic interactions of Mcpt1

  • The results are consistent with a model according to which the proteolytic degradation of LDL by mast cell granules results from coordinated action of the two granule-bound enzymes, whereby the chymase first cleaves peptides from the apolipoprotein B of LDL, and thereafter the carboxypeptidase A cleaves amino acids from the peptides formed [14].

Regulatory relationships of Mcpt1


Other interactions of Mcpt1

  • A computer search for homology indicates 73% and 33% sequence identity of RMCP I with rat mast cell protease II from mucosal mast cells and bovine chymotrypsin A, respectively [7].
  • RESULTS: Acute stress increased skin vascular permeability and CRH content, while it decreased RMCP-1 [16].
  • However, recent evidence indicates the existence of an alternative chymase-mediated biosynthetic pathway leading to the production of an ET-1[1-31] peptide, which was found to reproduce the ETA receptor-mediated vascular effects of ET-1[1-21] [17].
  • Moreover, rMCP-4 hydrolyzed MeO-Suc-Arg-Ala-Tyr-pNA, thus verifying that this protease belongs to the chymase family. rMCP-4 bound to heparin, and the enzymatic activity toward MeO-Suc-Arg-Ala-Tyr-pNA was strongly enhanced in the presence of heparin [18].
  • Neither phosphoramidon nor chymostatin, a chymase inhibitor, influenced the generation of DAG evoked by big ET-1 [19].

Analytical, diagnostic and therapeutic context of Mcpt1


  1. A novel vascular smooth muscle chymase is upregulated in hypertensive rats. Guo, C., Ju, H., Leung, D., Massaeli, H., Shi, M., Rabinovitch, M. J. Clin. Invest. (2001) [Pubmed]
  2. Chymase inhibition prevents cardiac fibrosis and dysfunction after myocardial infarction in rats. Kanemitsu, H., Takai, S., Tsuneyoshi, H., Nishina, T., Yoshikawa, K., Miyazaki, M., Ikeda, T., Komeda, M. Hypertens. Res. (2006) [Pubmed]
  3. Mucosal mast cells are functionally active during spontaneous expulsion of intestinal nematode infections in rat. Woodbury, R.G., Miller, H.R., Huntley, J.F., Newlands, G.F., Palliser, A.C., Wakelin, D. Nature (1984) [Pubmed]
  4. Release of the mucosal mast cell granule chymase, rat mast cell protease-II, during anaphylaxis is associated with the rapid development of paracellular permeability to macromolecules in rat jejunum. Scudamore, C.L., Thornton, E.M., McMillan, L., Newlands, G.F., Miller, H.R. J. Exp. Med. (1995) [Pubmed]
  5. Angiotensin II-forming activity in a reconstructed ancestral chymase. Chandrasekharan, U.M., Sanker, S., Glynias, M.J., Karnik, S.S., Husain, A. Science (1996) [Pubmed]
  6. Secretory granule proteases in rat mast cells. Cloning of 10 different serine proteases and a carboxypeptidase A from various rat mast cell populations. Lützelschwab, C., Pejler, G., Aveskogh, M., Hellman, L. J. Exp. Med. (1997) [Pubmed]
  7. Amino acid sequence of rat mast cell protease I (chymase). Le Trong, H., Parmelee, D.C., Walsh, K.A., Neurath, H., Woodbury, R.G. Biochemistry (1987) [Pubmed]
  8. Transgenic study of the function of chymase in heart remodeling. Chen, L.Y., Li, P., He, Q., Jiang, L.Q., Cui, C.J., Xu, L., Liu, L.S. J. Hypertens. (2002) [Pubmed]
  9. Substrate specificity of the chymotrypsin-like protease in secretory granules isolated from rat mast cells. Le Trong, H., Neurath, H., Woodbury, R.G. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  10. Role of chymase-dependent angiotensin II formation in monocrotaline-induced pulmonary hypertensive rats. Kishi, K., Jin, D., Takai, S., Muramatsu, M., Katayama, H., Tamai, H., Miyazaki, M. Pediatr. Res. (2006) [Pubmed]
  11. Molecular cloning of rat mast cell protease 1 and development of specific probes for its gene transcript. Rouleau, A., Garbarg, M., Schwartz, J.C., Ruat, M. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  12. Chymase in exocytosed rat mast cell granules effectively proteolyzes apolipoprotein AI-containing lipoproteins, so reducing the cholesterol efflux-inducing ability of serum and aortic intimal fluid. Lindstedt, L., Lee, M., Castro, G.R., Fruchart, J.C., Kovanen, P.T. J. Clin. Invest. (1996) [Pubmed]
  13. Regulation of intestinal mast cells and luminal protein release by cerebral thyrotropin-releasing hormone in rats. Santos, J., Saperas, E., Mourelle, M., Antolín, M., Malagelada, J.R. Gastroenterology (1996) [Pubmed]
  14. Low density lipoprotein degradation by secretory granules of rat mast cells. Sequential degradation of apolipoprotein B by granule chymase and carboxypeptidase A. Kokkonen, J.O., Vartiainen, M., Kovanen, P.T. J. Biol. Chem. (1986) [Pubmed]
  15. Inhibition of rat mast cell protease 1 by vitronectin. Pejler, G., Tomasini-Johansson, B.R. FEBS Lett. (1994) [Pubmed]
  16. Acute stress results in skin corticotropin-releasing hormone secretion, mast cell activation and vascular permeability, an effect mimicked by intradermal corticotropin-releasing hormone and inhibited by histamine-1 receptor antagonists. Lytinas, M., Kempuraj, D., Huang, M., Boucher, W., Esposito, P., Theoharides, T.C. Int. Arch. Allergy Immunol. (2003) [Pubmed]
  17. Endothelin-1[1-31] acts as a selective ETA-receptor agonist in the rat adrenal cortex. Rebuffat, P., Malendowicz, L.K., Neri, G., Nussdorfer, G.G. Histol. Histopathol. (2001) [Pubmed]
  18. Rat mast cell protease 4 is a beta-chymase with unusually stringent substrate recognition profile. Karlson, U., Pejler, G., Froman, G., Hellman, L. J. Biol. Chem. (2002) [Pubmed]
  19. The effect of big endothelin-1 in the proximal tubule of the rat kidney. Beara-Lasić, L., Knotek, M., Cejvan, K., Jaksić, O., Lasić, Z., Skorić, B., Brkljacić, V., Banfić, H. Br. J. Pharmacol. (1997) [Pubmed]
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