Neuropeptide Inactivation By Peptidases
Gerard O’Cuinn in Metabolism of Brain Peptides, 2020
Endopeptidase 24.11 (E.C. 3.4.24.11) is a widely distributed membrane-bound neutral endopeptidase which is active against a range of naturally occurring peptide substrates. It was first isolated by Kerr and Kenny from rabbit kidney34. Other workers showed that the endopeptidase activity from brain had similar physiochemical properties to the kidney enzyme where it was termed 'enkephalinase' because of its ability to degrade Met - and Leu - enkephalin35. This name was later shown to be a misnomer as it became clear that the enzyme was capable of cleaving a variety of peptides including the enkephalins, angiotensin I, tachykinins, LH-RH, neurotensin, bradykinin, interleukin-1, substance P, neurokinin A, atrial natriuretic factor and the endothelins36–38. Several other titles were given to the enzyme including 'Neprilysin'39 and neutral endopeptidase 24.1140. In 1983 it was given the title 'endopeptidase 24.11' based on its E.C. number41. More recently in the plasma membranes of many tissues it has been shown to be identical to the common acute lymphoblastic leukemia antigen (CALLA) also known as the CD 10 antigen42.
Enzymatic Degradation of Bradykinin
Sami I. Said in Proinflammatory and Antiinflammatory Peptides, 2020
Because of its wide distribution, NEP’s role in vivo can differ in each organ with the different substrates. The skeletal muscle of the dog contains high concentrations of NEP, in contrast to other species where it is lower (Dragovic et al., 1996). Similar to ACE, the importance of the highly active NEP in the male genital tract, especially in prostate glands (Erdös et al., 1985), is not yet known. NEP has also been the subject of many studies, but under the names CALLA (common acute lymphoblastic leukemia antigen) or CD 10 (Letarte et al., 1988; LeBien and McCormack, 1989). CALLA is present in lymphoblasts but is absent from mature lymphocytes. In contrast, it is in neutrophils but absent from progenitor cells (Connelly et al., 1985; Painter et al., 1988). Because of its presence in neutrophils and synovial fibroblasts (Werb and Clark, 1989) and in respiratory tract (Nadel, 1994), it may be an important factor in breaking down inflammatory peptides.
Adipose Tissue-Derived Adult Stem Cells
Richard K. Burt, Alberto M. Marmont in Stem Cell Therapy for Autoimmune Disease, 2019
After expansion in culture, the primary isolated human ADAS cells display a distinct phenotype based on cell surface protein expression (characterized by flow cytometric analysis) and cytokine expression (characterized by polymerase chain reaction and ELISA) (Table 2). The profile is similar, but not identical, to that described for human bone marrow stromal cells.10 For example, unlike human bone marrow stromal cells, ADAS cells do not express the STRO-1 (a marker of osteoprogenitor stem cells) surface antigen or the interleukin 1 cytokines.10,21 The ADAS surface protein phenotype is also similar to that described for skeletal muscle derived adult stem cells. 14a,b Both populations express the common acute lymphoblastic leukemia antigen (CD10), aminopeptidase (CD13), and the major histocompatibility antigen class I; however, unlike muscle derived adult stem cells, ADAS cells do not express the neural cell adhesion molecule or N-CAM (CD56).14a,22
What do we know about the renin angiotensin system and inflammatory bowel disease?
Published in Expert Opinion on Therapeutic Targets, 2022
Sheng Wei Lo, Jonathan P. Segal, John S. Lubel, Mayur Garg
Neutral endopeptidase (NEP), also known as neprilysin (CD10, common lymphoblastic leukemia antigen, enkephalinase), is a membrane-bound, zinc metalloproteinase, present in numerous organs, specifically the gastrointestinal secretory epithelial brush borders. Its role in the RAS includes the cleaving of Ang I to form Ang (1-7) that is independent of ACE2, and cleaving Ang II into inactive fragments. NEP inhibition is used, in conjunction with AT1R blockade, to reduce death from cardiovascular causes in heart failure with reduced ejection fraction, via its effects of vasodilatation and natriuresis [19]. On the other hand, Sargin et al reported anti-inflammatory effects of NEP activation in UC, via the hydrolysis of pro-inflammatory neuropeptides such as substance P, calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) [].
Biomarker and Invasive Hemodynamic Assessment of Cardiac Damage Class in Aortic Stenosis
Published in Structural Heart, 2021
James W. Lloyd, Allan S. Jaffe, Brian R. Lindman, Patricia A. Pellikka, Hector I. Michelena, Philippe Pibarot, Rick A. Nishimura, Barry A. Borlaug, Mackram F. Eleid
Preprocedural laboratory assessment was conducted shortly after procedure onset and before valve deployment. Acquired venous blood samples were evaluated for measures of myocardial injury (GDF-15, hs-CRP, and hs-cTnT); myocardial stress (neprilysin, NT-proBNP, and sST2); and myocardial remodeling (galectin-3). With the exception of neprilysin, all levels were measured by Mayo Clinic Laboratories (Rochester, MN). Neprilysin levels were measured by iCor Research Lab (Barcelona, Spain). Galectin-3 was measured via enzyme-linked immunosorbent assay (ELISA) (BG Medicine, Waltham, MA); GDF-15 via ELISA (R&D Systems, Minneapolis, MN); hs-CRP via immunoturbidimetry (Roche Diagnostics, Indianapolis, IN); hs-cTnT via electrochemiluminescence assay (ELICA) (Roche Diagnostics, Indianapolis, IN); neprilysin via ELISA (Aviscera Bioscience, Santa Clara, CA); NT-proBNP via ELICA (Roche Diagnostics, Indianapolis, IN); and sST2 via quantitative 2-site ELISA (Critical Diagnostics, San Diego, CA). Cutoff values for abnormal biomarker levels were assigned based on previous associations with cardiovascular dysfunction (in heart failure and/or aortic stenosis) and included galectin-3 (≤ 17.8 ng/mL),10 GDF-15 (< 2567 pg/mL),17 hs-CRP (< 2.0 mg/dL),28 hs-cTnT (< 14 ng/L),29 neprilysin (< 645 pg/mL),30 NT-proBNP (age-specific cutoffs of ≤ 450 pg/mL for individuals < 50, ≤ 900 for individuals 50–75, and ≤ 1800 for individuals > 75),31 and sST2 (< 35.0 ng/mL).32
Novel heart failure biomarkers: why do we fail to exploit their potential?
Published in Critical Reviews in Clinical Laboratory Sciences, 2018
Arnold Piek, Weijie Du, Rudolf A. de Boer, Herman H. W. Silljé
The levels of natriuretic peptides can be influenced by other syndromes and diseases, and kidney dysfunction is an important factor that may elevate natriuretic peptide levels [31]. In addition, obesity may be associated with lower natriuretic peptide concentrations and this may modestly reduce the diagnostic sensitivity in morbidly obese patients [32]. Importantly, with the positive results of clinical HF trials with entresto (LCZ-696) [33,34], the introduction of this drug in daily clinical HF practice will make the interpretation of BNP levels in such treated patients more difficult. Entresto is made up of the angiotensin-receptor blocker (ARB), valsartan, and the neprilysin inhibitor prodrug, sacubitril; the latter inhibits degradation of natriuretic peptides, thereby enhancing their beneficial effect during cardiac stress [35]. The concept that the lower the BNP levels in chronic HF patients, the better the prognosis during treatment monitoring will no longer hold true in these patients. Because NT-proBNP and MR-proANP are not subject to breakdown by neprilysin, these biomarkers can still be used for patient monitoring in this setting [36].
Related Knowledge Centers
- Bradykinin
- Enkephalin
- Enzyme
- Metalloproteinase
- Oxytocin
- Peptide
- Substance P
- Zinc
- Glucagon
- Neurotensin