<b>Characterization of a soluble form of neutral endopeptidase‐24.11 (EC 3.4.24.11) in human serum: enhancement of its activity in serum of underground miners exposed to coal dust particles</b>

Soleilhac, Jean-Marc; Lafuma, C.; Porcher, Jean‐Marc; Auburtin, Guy; Roques, B P

doi:10.1046/j.1365-2362.1996.2420580.x

Cited by 15 publications

(12 citation statements)

References 22 publications

(31 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This speculation is supported by several previous studies that increased NEP activities in serum were observed from underground miners exposed to coal dust particles (Soleilhac et al, 1996) or patients with pulmonary inflammatory diseases, such as sarcoidosis and adult respiratory distress syndrome (Johnson et al, 1985; Almenoff et al,1986). Increased NEP activities in serum may reflect local tissue damage with subsequent shedding of membrane-bound enzymes and an abnormal release from the airways in response to lung injury (Soleilhac et al, 1996). In this study, significant increases of soluble NEP activity following exposures suggest that membrane-bound NEP in airways was modified or impaired structurally and functionally.…”

Section: Discussionsupporting

confidence: 64%

Acute changes in sputum collected from exposed human subjects in mining conditions

Wong

Sun

Miller

et al. 2010

Inhalation Toxicology

View full text Add to dashboard Cite

Neprilysin (NEP) is a key cell surface peptidase in the maintenance of airway homeostasis and the development of pulmonary disorders. However, little information is available about the effect of particulate matter (PM) on airway NEP. In this controlled human exposure study, changes in induced sputum were measured in eleven subjects at baseline, overshot (OS) mucking, and diesel exhaust (DE) exposure days. Neither OS condition nor DE exposure was found to induce significant changes in total protein, but DE induced significant increases in cell numbers of macrophages and epithelium. Moreover, significant increases in soluble NEP were observed following OS mining dust particulates (0.43 ± 0.06, p = 0.023) and DE exposure (0.30 ± 0.04, p = 0.035) when compared with the baseline control (0.40 ± 0.03), with 42% and 31% average net increase, respectively. Pearson’s correlation analyses indicated that sputum NEP activity were significantly associated with personal exposure product [Elemental carbon concentration, mg/m3 X time, min. (C X T)]. Data suggest that the changes in NEP activity may be an early, accurate endpoint for airway epithelial injury and provided a new insight into the mechanism of the airway effects in these exposure conditions.

show abstract

Section: Discussionsupporting

confidence: 64%

Acute changes in sputum collected from exposed human subjects in mining conditions

Wong

Sun

Miller

et al. 2010

Inhalation Toxicology

View full text Add to dashboard Cite

show abstract

“…Infusion of the metalloprotease inhibitor thiorphan into the hippocampus of rats resulted in a significant increase in the amount of A␤ and in the deposition of the longer more amyloidogenic form, A␤42, reportedly through the inhibition of A␤ degradation by NEP. NEP and ACE have been reported to reside predominantly on the cell surface, although a soluble form of NEP is also present in serum and cerebral spinal fluid (43)(44)(45)(46). A recently identified thiorphan-sensitive NEP homo-logue SEP/NL1/NEPII is expressed both as a membrane-bound and secreted protease (47)(48)(49).…”

Section: Resultsmentioning

confidence: 99%

Degradation of the Alzheimer's Amyloid β Peptide by Endothelin-converting Enzyme

Eckman

Reed

Eckman

2001

Journal of Biological Chemistry

316

245

View full text Add to dashboard Cite

Deposition of ␤-amyloid (A␤) peptides in the brain is an early and invariant feature of all forms of Alzheimer's disease. As with any secreted protein, the extracellular concentration of A␤ is determined not only by its production but also by its catabolism. A major focus of Alzheimer's research has been the elucidation of the mechanisms responsible for the generation of A␤. Much less, however, is known about the mechanisms responsible for A␤ removal in the brain. In this report, we describe the identification of endothelin-converting enzyme-1 (ECE-1) as a novel A␤-degrading enzyme. We show that treatment of endogenous ECE-expressing cell lines with the metalloprotease inhibitor phosphoramidon causes a 2-3-fold elevation in extracellular A␤ concentration that appears to be due to inhibition of intracellular A␤ degradation. Furthermore, we show that overexpression of ECE-1 in Chinese hamster ovary cells, which lack endogenous ECE activity, reduces extracellular A␤ concentration by up to 90% and that this effect is completely reversed by treatment of the cells with phosphoramidon. Finally, we show that recombinant soluble ECE-1 is capable of hydrolyzing synthetic A␤40 and A␤42 in vitro at multiple sites.

show abstract

“…23 Possible cellular origin of soluble NEP are neutrophils and alveolar epithelial cells. 31 NEP is known to be an integral membrane protease, and the mechanism for the release of a soluble form is unknown. One possible origin of soluble NEP is by the shedding process, which occurs in many eukaryotic cells with membrane-bound proteins being released with portions of plasma membrane or as proteolipid aggregates.…”

Section: Discussionmentioning

confidence: 99%

Neutral endopeptidase and angiotensin I converting enzyme insertion/deletion gene polymorphism in humans

Oliveri

et al. 2004

J Hum Hypertens

View full text Add to dashboard Cite

Neutral endopeptidase (NEP) hydrolyses angiotensins (Ang) I and II and generates angiotensin-(1-7) ]. In humans, the insertion/deletion (I/D) angiotensin-I converting enzyme (ACE) gene polymorphism determined plasma ACE levels by 40%. In rats, a similar polymorphism determines ACE levels which are inversely associated to NEP activity. The objective of this study is to evaluate the relationship between ACE expression and plasma NEP activity in normotensive subjects and in hypertensive patients. In total, 58 consecutive patients with hypertension, evaluated in our Hypertension Clinic, were compared according to their ACE I/D genotypes with 54 control subjects in terms of both plasma ACE activity and NEP activities. Plasma ACE activity was elevated 51 and 70% in both DD ACE groups (normotensives and hypertensives) compared with their respective ID and II ACE groups (Po0.001). A significant effect of the ACE polymorphism and of the hypertensive status on ACE activity was observed (Po0.001). In normotensive DD ACE subjects, NEP activity was 0.30 7 0.02 U/ml, whereas in the normotensive II ACE and in the normotensive ID ACE subjects NEP activity was increased 65 and 48%, respectively (Po0.001). In the hypertensive DD ACE patients, NEP activity was 0.47 7 0.03 U/mg. An effect of the I/D ACE genotypes on NEP activity (Po0.04) and an interaction effect between the I/D ACE genotype and the hypertensive status were also observed (Po0.001). These results are consistent with a normal and inverse relationship between the ACE polymorphism and NEP activity in normotensive humans (as is also observed in rats). This normal relationship is not observed in hypertensive patients.

show abstract

Characterization of a soluble form of neutral endopeptidase‐24.11 (EC 3.4.24.11) in human serum: enhancement of its activity in serum of underground miners exposed to coal dust particles

Cited by 15 publications

References 22 publications

Acute changes in sputum collected from exposed human subjects in mining conditions

Acute changes in sputum collected from exposed human subjects in mining conditions

Degradation of the Alzheimer's Amyloid β Peptide by Endothelin-converting Enzyme

Neutral endopeptidase and angiotensin I converting enzyme insertion/deletion gene polymorphism in humans

Contact Info

Product

Resources

About