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ECE1  -  endothelin converting enzyme 1

Homo sapiens

Synonyms: ECE-1, Endothelin-converting enzyme 1
 
 
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Disease relevance of ECE1

 

Psychiatry related information on ECE1

 

High impact information on ECE1

  • This mutation prevents the proteolytic activation of big EDN3 by ECE-1 [6].
  • We examined the contribution of endogenously generated endothelin-1 to maintenance of peripheral vascular tone in healthy subjects by local intraarterial administration of an inhibitor of endothelin converting enzyme, phosphoramidon, and of a selective endothelin receptor A antagonist, BQ-123 [7].
  • The presence of preproET-1 and human endothelin-converting enzyme-1 (hECE-1) mRNA was also investigated by reverse transcription-polymerase chain reaction in homogenates of vessel wall, including preparations deprived of both endothelium and adventitia, and in isolated VSMCs [8].
  • PreproET-1 and hECE-1 mRNA was also detected in VSMCs isolated from these vessels. irET-1 and irvWF staining in endothelium and tunica media was measured by use of microscope-coupled computer-assisted technology [8].
  • A loss-of-function mutation in the endothelin-converting enzyme 1 (ECE-1) associated with Hirschsprung disease, cardiac defects, and autonomic dysfunction [9].
 

Chemical compound and disease context of ECE1

 

Biological context of ECE1

 

Anatomical context of ECE1

 

Associations of ECE1 with chemical compounds

 

Physical interactions of ECE1

 

Co-localisations of ECE1

  • ECE-1 immunostaining was colocalized to big ET-1 and ET-1 immunostaining, and correlated with disease activity (P < 0.05) [19].
 

Regulatory relationships of ECE1

  • Consequently, ECE inhibitors are expected to suppress the biosynthesis of ET-1 and reduce the pathologic impact resulting from overproduction of this peptide [20].
  • In summary, ET-1 production in RPE is regulated by at least two isoforms of ECE, (cytosolic and PM) as well as cathepsins [21].
  • These results suggest ECE-1b and ECE-2 may be widely expressed in normal tissue from humans and inhibition of ECE-1 isoforms and ECE-2 expressed by cells such as macrophages in pathophysiological tissue may be an additional therapeutic target in cardiovascular disease [22].
 

Other interactions of ECE1

  • To clarify the potential involvement of ECE in the processing and secretion of ET-1 by human keratinocytes, we synthesized the N-terminal peptide of human ECE-1alpha and generated a rabbit polyclonal antibody (alphaPEPT6) that specifically recognizes ECE-1alpha [1].
  • Differential expression of neutral endopeptidase-24.11 (neprilysin) and endothelin-converting enzyme in human prostate cancer cell lines [4].
  • There was no significant difference in mRNA expression for ppET-1, ECE-1, and ETA receptors, whereas a significant reduction of ETB-receptor mRNA was observed in DCM hearts [23].
  • A second enzyme, ECE-2, also exists as four isoforms and differs from ECE-1 in requiring an acidic pH for optimal activity [24].
  • In conclusion, prior cleavage at Arg92 by furin-like convertase is absolutely necessary for cleavage by ECE-1 at Trp73 to produce mature endothelin-1 [25].
 

Analytical, diagnostic and therapeutic context of ECE1

  • Therefore, we tested the influence of the coculture on endothelin-converting enzyme-1 (ECE-1), and found a significant reduction of its mRNA and protein levels as well as a decreased activity in HuVEC/HMC as compared to HuVEC alone [16].
  • Administration of an ECE inhibitor (CGS 26303, 30 mg/kg) significantly reduced the blood pressure in the Ad.CMV.secECE + Ad.CMV.ET-1 group (from 125 +/- 5 to 74 +/- 6 mm Hg) but not in the control group (from 85 +/- 2 to 75 +/- 3 mm Hg) [26].
  • The increase in ECE-1 expression was inhibited in both cell cultures by GF109203X (5 micromol/l), a general PKC inhibitor, while addition of 10 nmol/l phorbol myristic acid to EA.hy926 cells or HUVEC growing on medium containing 5.5 mmol/l glucose increased ECE-1 expression to a level similar to that of cells conditioned in high glucose [27].
  • METHODS AND RESULTS: To evaluate ECE-1 immunoreactivity concerning big ET-1/ET-1, we performed qualitative and quantitative immunohistochemistry in normal internal mammary arteries (n=10), in coronary arteries with adaptive intimal fibrosis (n=10), in aortic fatty streaks (n=10), and in distinct regions of advanced carotid plaques (n=15) [28].
  • Using gel filtration chromatography, we separated two distinct ECE activities, designated M1 (apparent molecular mass approx. 300 kDa) and M2 (approx. 65 kDa) [29].

References

  1. Biochemical characterization of endothelin-converting enzyme-1alpha in cultured skin-derived cells and its postulated role in the stimulation of melanogenesis in human epidermis. Hachiya, A., Kobayashi, T., Takema, Y., Imokawa, G. J. Biol. Chem. (2002) [Pubmed]
  2. Endothelin system in oral squamous carcinoma cells: specific siRNA targeting of ECE-1 blocks cell proliferation. Awano, S., Dawson, L.A., Hunter, A.R., Turner, A.J., Usmani, B.A. Int. J. Cancer (2006) [Pubmed]
  3. The endothelin system in human glioblastoma. Egidy, G., Eberl, L.P., Valdenaire, O., Irmler, M., Majdi, R., Diserens, A.C., Fontana, A., Janzer, R.C., Pinet, F., Juillerat-Jeanneret, L. Lab. Invest. (2000) [Pubmed]
  4. Differential expression of neutral endopeptidase-24.11 (neprilysin) and endothelin-converting enzyme in human prostate cancer cell lines. Usmani, B.A., Harden, B., Maitland, N.J., Turner, A.J. Clin. Sci. (2002) [Pubmed]
  5. Alzheimer's disease beta-amyloid peptide is increased in mice deficient in endothelin-converting enzyme. Eckman, E.A., Watson, M., Marlow, L., Sambamurti, K., Eckman, C.B. J. Biol. Chem. (2003) [Pubmed]
  6. Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons. Baynash, A.G., Hosoda, K., Giaid, A., Richardson, J.A., Emoto, N., Hammer, R.E., Yanagisawa, M. Cell (1994) [Pubmed]
  7. Contribution of endogenous generation of endothelin-1 to basal vascular tone. Haynes, W.G., Webb, D.J. Lancet (1994) [Pubmed]
  8. Endothelin-1 and its mRNA in the wall layers of human arteries ex vivo. Rossi, G.P., Colonna, S., Pavan, E., Albertin, G., Della Rocca, F., Gerosa, G., Casarotto, D., Sartore, S., Pauletto, P., Pessina, A.C. Circulation (1999) [Pubmed]
  9. A loss-of-function mutation in the endothelin-converting enzyme 1 (ECE-1) associated with Hirschsprung disease, cardiac defects, and autonomic dysfunction. Hofstra, R.M., Valdenaire, O., Arch, E., Osinga, J., Kroes, H., Löffler, B.M., Hamosh, A., Meijers, C., Buys, C.H. Am. J. Hum. Genet. (1999) [Pubmed]
  10. SLV-306. Solvay. Tabrizchi, R. Current opinion in investigational drugs (London, England : 2000) (2003) [Pubmed]
  11. Regulation of endothelin-converting enzyme-1 expression in human neuroblastoma cells. Fisk, L., Nalivaeva, N.N., Turner, A.J. Exp. Biol. Med. (Maywood) (2006) [Pubmed]
  12. Genes encoding endothelin-converting enzyme-1 and endothelin-1 interact to influence blood pressure in women: the EVA study. Funalot, B., Courbon, D., Brousseau, T., Poirier, O., Berr, C., Cambien, F., Amouyel, P., Schwartz, J.C., Ducimetière, P. J. Hypertens. (2004) [Pubmed]
  13. Molecular pharmacology of endothelin converting enzymes. Turner, A.J., Murphy, L.J. Biochem. Pharmacol. (1996) [Pubmed]
  14. Endothelin converting enzyme (ECE) activity in human vascular smooth muscle. Maguire, J.J., Johnson, C.M., Mockridge, J.W., Davenport, A.P. Br. J. Pharmacol. (1997) [Pubmed]
  15. Angiotensin-converting enzyme inhibitor therapy prevents upregulation of endothelin-converting enzyme-1 in failing human myocardium. Morawietz, H., Goettsch, W., Szibor, M., Barton, M., Shaw, S., Hakim, K., Zerkowski, H.R., Holtz, J. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  16. Crosstalk between mesangial and endothelial cells: angiotensin II down-regulates endothelin-converting enzyme 1. López-Ongil, S., Díez-Marqués, M.L., Griera, M., Rodríguez-Puyol, M., Rodríguez-Puyol, D. Cell. Physiol. Biochem. (2005) [Pubmed]
  17. Development of an internally quenched fluorescent substrate selective for endothelin-converting enzyme-1. Johnson, G.D., Ahn, K. Anal. Biochem. (2000) [Pubmed]
  18. Shear stress attenuates endothelin and endothelin-converting enzyme expression through oxidative stress. Masatsugu, K., Itoh, H., Chun, T.H., Saito, T., Yamashita, J., Doi, K., Inoue, M., Sawada, N., Fukunaga, Y., Sakaguchi, S., Sone, M., Yamahara, K., Yurugi, T., Nakao, K. Regul. Pept. (2003) [Pubmed]
  19. Elevated expression of endothelin-1 and endothelin-converting enzyme-1 in idiopathic pulmonary fibrosis: possible involvement of proinflammatory cytokines. Saleh, D., Furukawa, K., Tsao, M.S., Maghazachi, A., Corrin, B., Yanagisawa, M., Barnes, P.J., Giaid, A. Am. J. Respir. Cell Mol. Biol. (1997) [Pubmed]
  20. Attenuation of hemolysate-induced cerebrovascular endothelial cell injury and of production of endothelin-1 and big endothelin-1 by an endothelin-converting enzyme inhibitor. Chang, C.Z., Winardi, D., Lin, C.L., Kwan, A.L., Jeng, A.Y., Kassell, N.F., Howng, S.L., Lee, K.S. Surgical neurology. (2002) [Pubmed]
  21. Characterization of endothelin-converting enzyme activities in ARPE-19 cells, a human retinal pigmented epithelial cell line. Dibas, A., Prasanna, G., Yorio, T. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics. (2005) [Pubmed]
  22. Cellular expression of isoforms of endothelin-converting enzyme-1 (ECE-1c, ECE-1b and ECE-1a) and endothelin-converting enzyme-2. Davenport, A.P., Kuc, R.E. J. Cardiovasc. Pharmacol. (2000) [Pubmed]
  23. Expression of endothelin-1, endothelin-converting enzyme, and endothelin receptors in chronic heart failure. Zolk, O., Quattek, J., Sitzler, G., Schrader, T., Nickenig, G., Schnabel, P., Shimada, K., Takahashi, M., Böhm, M. Circulation (1999) [Pubmed]
  24. Endothelin. Davenport, A.P., Maguire, J.J. Handbook of experimental pharmacology. (2006) [Pubmed]
  25. Processing of proendothelin-1 at the C-terminus of big endothelin-1 is essential for proteolysis by endothelin-converting enzyme-1 in vivo. Kido, T., Sawamura, T., Hoshikawa, H., D'Orléans-Juste, P., Denault, J.B., Leduc, R., Kimura, J., Masaki, T. Eur. J. Biochem. (1997) [Pubmed]
  26. In vivo role of endothelin-converting enzyme-1 as examined by adenovirus-mediated overexpression in rats. Télémaque, S., Emoto, N., deWit, D., Yanagisawa, M. J. Cardiovasc. Pharmacol. (1998) [Pubmed]
  27. Increased expression of endothelin-converting enzyme-1c isoform in response to high glucose levels in endothelial cells. Keynan, S., Khamaisi, M., Dahan, R., Barnes, K., Jackson, C.D., Turner, A.J., Raz, I. J. Vasc. Res. (2004) [Pubmed]
  28. Coexpression of endothelin-converting enzyme-1 and endothelin-1 in different stages of human atherosclerosis. Ihling, C., Szombathy, T., Bohrmann, B., Brockhaus, M., Schaefer, H.E., Loeffler, B.M. Circulation (2001) [Pubmed]
  29. Characterization of phosphoramidon-sensitive metalloproteinases with endothelin-converting enzyme activity in porcine lung membrane. Sawamura, T., Shinmi, O., Kishi, N., Sugita, Y., Yanagisawa, M., Goto, K., Masaki, T., Kimura, S. Biochim. Biophys. Acta (1993) [Pubmed]
 
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