scholarly journals Erratum: Corrigendum: N-terminal domain of Bothrops asper Myotoxin II Enhances the Activity of Endothelin Converting Enzyme-1 and Neprilysin

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
A. Ian Smith ◽  
Niwanthi W. Rajapakse ◽  
Oded Kleifeld ◽  
Bruno Lomonte ◽  
Nkumbu L. Sikanyika ◽  
...  
Keyword(s):  
Converting Enzyme ◽  
Terminal Domain ◽  
Endothelin Converting Enzyme ◽  
Bothrops Asper

scholarly journals N-terminal domain of Bothrops asper Myotoxin II Enhances the Activity of Endothelin Converting Enzyme-1 and Neprilysin

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
A. Ian Smith ◽  
Niwanthi W. Rajapakse ◽  
Oded Kleifeld ◽  
Bruno Lomonte ◽  
Nkumbu L. Sikanyika ◽  
...  
Keyword(s):  
Amyloid Beta ◽  
Fold Increase ◽  
Converting Enzyme ◽  
Drug Lead ◽  
Excellent Research ◽  
Endothelin Converting Enzyme ◽  
Enzyme Stimulation ◽  
Bothrops Asper ◽  
Novel Drug ◽  
The Brain

Abstract Neprilysin (NEP) and endothelin converting enzyme-1 (ECE-1) are two enzymes that degrade amyloid beta in the brain. Currently there are no molecules to stimulate the activity of these enzymes. Here we report, the discovery and characterisation of a peptide referred to as K49-P1-20, from the venom of Bothrops asper which directly enhances the activity of both ECE-1 and NEP. This is evidenced by a 2- and 5-fold increase in the Vmax of ECE-1 and NEP respectively. The K49-P1-20 concentration required to achieve 50% of maximal stimulation (AC50) of ECE-1 and NEP was 1.92 ± 0.07 and 1.33 ± 0.12 μM respectively. Using BLITZ biolayer interferometry we have shown that K49-P1-20 interacts directly with each enzyme. Intrinsic fluorescence of the enzymes change in the presence of K49-P1-20 suggesting a change in conformation. ECE-1 mediated reduction in the level of endogenous soluble amyloid beta 42 in cerebrospinal fluid is significantly higher in the presence of K49-P1-20 (31 ± 4% of initial) compared with enzyme alone (11 ± 5% of initial; N = 8, P = 0.005, unpaired t-test). K49-P1-20 could be an excellent research tool to study mechanism(s) of enzyme stimulation, and a potential novel drug lead in the fight against Alzheimer’s disease.

Expression of human endothelin-converting enzyme isoforms: role of angiotensin IIThis article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.

2008 ◽  
Vol 86 (6) ◽  
pp. 299-309 ◽  
Author(s):  
W. Goettsch ◽  
A. Schubert ◽  
H. Morawietz
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Umbilical Vein ◽  
Artery Bypass ◽  
Control Group ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Mammary Arteries ◽  
Endothelin Converting Enzyme ◽  
Internal Mammary

A key step in endothelin-1 (ET-1) synthesis is the proteolytic cleavage of big ET-1 by the endothelin-converting enzyme-1 (ECE-1). Four alternatively spliced isoforms, ECE-1a to ECE-1d, have been discovered; however, regulation of the expression of specific ECE-1 isoforms is not well understood. Therefore, we stimulated primary human umbilical vein endothelial cells (HUVECs) with angiotensin II (Ang II). Furthermore, expression of ECE-1 isoforms was determined in internal mammary arteries of patients undergoing coronary artery bypass grafting surgery. Patients had received one of 4 therapies: angiotensin-converting enzyme inhibitors (ACE-I), Ang II type 1 receptor blockers (ARB), HMG-CoA reductase inhibitors (statins), and a control group that had received neither ACE-I, ARB (that is, treatment not interfering in the renin–angiotensin system), nor statins. Under control conditions, ECE-1a is the dominant isoform in HUVECs (4.5 ± 2.8 amol/μg RNA), followed by ECE-1c (2.7 ± 1.0 amol/μg), ECE-1d (0.49 ± 0.17 amol/μg), and ECE-1b (0.17 ± 0.04 amol/μg). Stimulation with Ang II did not change the ECE-1 expression pattern or the ET-1 release. We found that ECE-1 mRNA expression was higher in patients treated with statins than in patients treated with ARB therapy (5.8 ± 0.76 RU versus 3.0 ± 0.4 RU), mainly attributed to ECE-1a. In addition, ECE-1a mRNA expression was higher in patients receiving ACE-I therapy than in patients receiving ARB therapy (1.68 ± 0.27 RU versus 0.83 ± 0.07 RU). We conclude that ECE-1a is the major ECE-1 isoform in primary human endothelial cells. Its expression in internal mammary arteries can be regulated by statin therapy and differs between patients with ACE-I and ARB therapy.

Design and Synthesis of Potent, Selective Inhibitors of Endothelin-Converting Enzyme

1998 ◽  
Vol 41 (9) ◽  
pp. 1513-1523 ◽  
Author(s):  
Eli M. Wallace ◽  
John A. Moliterni ◽  
Michael A. Moskal ◽  
Alan D. Neubert ◽  
Nicholas Marcopulos ◽  
...  
Keyword(s):  
Converting Enzyme ◽  
Selective Inhibitors ◽  
Design And Synthesis ◽  
Endothelin Converting Enzyme

scholarly journals Endothelin-Converting Enzyme Inhibition Ameliorates Angiotensin II–Induced Cardiac Damage

Hypertension ◽  
2002 ◽  
Vol 40 (6) ◽  
pp. 840-846 ◽  
Author(s):  
Dominik N. Muller ◽  
Alexander Mullally ◽  
Ralf Dechend ◽  
Joon-Keun Park ◽  
Anette Fiebeler ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Enzyme Inhibition ◽  
Converting Enzyme ◽  
Cardiac Damage ◽  
Endothelin Converting Enzyme ◽  
Converting Enzyme Inhibition
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