scholarly journals Certain mouse strains are deficient in a kidney brush-border metallo-endopeptidase activity

1983 ◽  
Vol 209 (1) ◽  
pp. 251-255 ◽  
Author(s):  
J S Bond ◽  
J D Shannon ◽  
R J Beynon
Keyword(s):  
Brush Border ◽  
Inbred Mice ◽  
Neutral Endopeptidase ◽  
Renal Tissue ◽  
Mouse Strains ◽  
Ph Optimum ◽  
Brush Border Enzymes ◽  
Endogenous Inhibitors ◽  
Endopeptidase Activity ◽  
Proteinase A

Preparations of microvilli from kidneys of BALB/c mice contain an alkaline metallo-endopeptidase, meprin (metallo-endopeptidase from renal tissue). Certain genealogically related inbred mice are markedly deficient in meprin activity. The meprin-deficient strains (CBA/J and C3H/HeJ) exhibit normal levels of other brush-border enzymes: alkaline phosphatase, aminopeptidase M and another proteinase, a phosphoramidon-sensitive neutral endopeptidase. Meprin deficiency cannot be attributed to a shift in pH optimum and is unlikely to be due to the presence of endogenous inhibitors.

Identification and properties of a neuropeptide-degrading endopeptidase (neprilysin) of Ascaris suum muscle

Parasitology ◽  
1995 ◽  
Vol 111 (5) ◽  
pp. 599-608 ◽  
Author(s):  
M. Sajid ◽  
R. E. Isaac
Keyword(s):  
Metal Ion ◽  
Ascaris Suum ◽  
Significant Proportion ◽  
Neutral Endopeptidase ◽  
Integral Membrane Protein ◽  
Hydrolytic Activity ◽  
The Body ◽  
Ph Optimum ◽  
Muscle Enzyme ◽  
Endopeptidase Activity

SUMMARYWe have previously identified in membranes of the locomotory muscle of Ascaris suum a phosphoramidon-sensitive endopeptidase which hydrolyses the neuropeptide AF1 (Lys-Asn-Glu-Phe-Ile-Arg-Phe-NH2) by cleavage of the Glu3-Phe4 bond (Sajid & Isaac, 1994). We have determined the properties of this neuropeptide-degrading enzyme of A. suum muscle using AKH-I (ρGlu-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2) and [D-Ala2, Leu5]enkephalin as convenient endopeptidase substrates. Phosphoramidon, thiorphan and SQ 28603, potent inhibitors of mammalian neprilysin (neutral endopeptidase, endopeptidase 24.11), inhibited the endopeptidase activity towards AKH-I with IC50 values of 0·13 μM, 22 μM and 6·3 μM, respectively. Two other neprilysin inhibitors (SCH 32615 and SCH 39370) and the bivalent metal ion chelators, EDTA (1 mM) and 1, 10 bis-phenanthroline (1 mM) failed to inhibit the nematode enzyme. The endopeptidase had a neutral pH optimum and a significant proportion (45%)of the enzyme activity partitioned into the detergent-rich phase of Triton X-114, indicating that the enzyme is an integral membrane protein. The muscle enzyme also attacked [D-Ala2, Leu5]enkephalin cleaving the Gly3-Phe4 bond and this hydrolytic activity was inhibited by phosphoramidon and thiorphan (IC50, 0·28 ρM and 15·8 ρM, respectively) but not by EDTA and 1,10 bis-phenanthroline. The phosphoramidon-sensitive endopeptidase activity was detected on intact muscle cells prepared by collagenase treatment of the body wall musculature, indicating that endopeptidase is accessible to peptide molecules that interact with the cell surface.

scholarly journals Evaluation of Met-Val-Lys as a Renal Brush Border Enzyme-Cleavable Linker to Reduce Kidney Uptake of 68Ga-Labeled DOTA-Conjugated Peptides and Peptidomimetics

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3854 ◽  
Author(s):  
Shreya Bendre ◽  
Zhengxing Zhang ◽  
Hsiou-Ting Kuo ◽  
Julie Rousseau ◽  
Chengcheng Zhang ◽  
...  
Keyword(s):  
Brush Border ◽  
Ex Vivo ◽  
Neutral Endopeptidase ◽  
Amide Bond ◽  
Detection Sensitivity ◽  
Brush Border Enzymes ◽  
Positron Emission ◽  
Brush Border Enzyme ◽  
Renal Brush Border

High kidney uptake is a common feature of peptide-based radiopharmaceuticals, leading to reduced detection sensitivity for lesions adjacent to kidneys and lower maximum tolerated therapeutic dose. In this study, we evaluated if the Met-Val-Lys (MVK) linker could be used to lower kidney uptake of 68Ga-labeled DOTA-conjugated peptides and peptidomimetics. A model compound, [68Ga]Ga-DOTA-AmBz-MVK(Ac)-OH (AmBz: aminomethylbenzoyl), and its derivative, [68Ga]Ga-DOTA-AmBz-MVK(HTK01166)-OH, coupled with the PSMA (prostate-specific membrane antigen)-targeting motif of the previously reported HTK01166 were synthesized and evaluated to determine if they could be recognized and cleaved by the renal brush border enzymes. Additionally, positron emission tomography (PET) imaging, ex vivo biodistribution and in vivo stability studies were conducted in mice to evaluate their pharmacokinetics. [68Ga]Ga-DOTA-AmBz-MVK(Ac)-OH was effectively cleaved specifically by neutral endopeptidase (NEP) of renal brush border enzymes at the Met-Val amide bond, and the radio-metabolite [68Ga]Ga-DOTA-AmBz-Met-OH was rapidly excreted via the renal pathway with minimal kidney retention. [68Ga]Ga-DOTA-AmBz-MVK(HTK01166)-OH retained its PSMA-targeting capability and was also cleaved by NEP, although less effectively when compared to [68Ga]Ga-DOTA-AmBz-MVK(Ac)-OH. The kidney uptake of [68Ga]Ga-DOTA-AmBz-MVK(HTK01166)-OH was 30% less compared to that of [68Ga]Ga-HTK01166. Our data demonstrated that derivatives of [68Ga]Ga-DOTA-AmBz-MVK-OH can be cleaved specifically by NEP, and therefore, MVK can be a promising cleavable linker for use to reduce kidney uptake of radiolabeled DOTA-conjugated peptides and peptidomimetics.

Different diuresis-dependent excretions of urinary enzymes: N-acetyl-beta-D-glucosaminidase, alanine aminopeptidase, alkaline phosphatase, and gamma-glutamyltransferase.

1986 ◽  
Vol 32 (3) ◽  
pp. 529-532 ◽  
Author(s):  
K Jung ◽  
G Schulze ◽  
C Reinholdt
Keyword(s):  
Alkaline Phosphatase ◽  
Brush Border ◽  
Excretion Rate ◽  
Urine Flow ◽  
High Intake ◽  
Brush Border Enzymes ◽  
Urinary Creatinine ◽  
Gamma Glutamyltransferase ◽  
Alanine Aminopeptidase ◽  
Brush Border Enzyme

Abstract We studied how much of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30) and of the brush-border enzymes alanine aminopeptidase (EC 3.4.11.2), alkaline phosphatase (EC 3.1.3.1), and gamma-glutamyltransferase (EC 2.3.2.2) was excreted in urine over 8 h after a high intake of fluid (22 mL per kilogram of body weight). The hourly excretion of all four enzymes increased with the increasing urine flow rate. The excretion rate of the brush-border enzymes was more markedly influenced than that of N-acetyl-beta-D-glucosaminidase. By relating the enzyme excretion to urinary creatinine we could reduce the variability of brush-border enzyme output and could completely compensate for the effect of diuresis on the excretion of N-acetyl-beta-D-glucosaminidase.

Serum neutral endopeptidase activity in patients with primary biliary cirrhosis

1998 ◽  
Vol 114 ◽  
pp. A1258
Author(s):  
K. Horvát-Karajz ◽  
F. Szalay ◽  
P. Lakatos ◽  
L. Selmeci ◽  
A. Csepregi ◽  
...  
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Neutral Endopeptidase ◽  
Biliary Cirrhosis ◽  
Endopeptidase Activity

Enzymatic Cleavage of Thymopoietin Oligopeptides by Pancreatic and Intestinal Brush-Border Enzymes

Peptides ◽  
1996 ◽  
Vol 17 (7) ◽  
pp. 1083-1089 ◽  
Author(s):  
J. HEIZMANN ◽  
P. LANGGUTH ◽  
A. BIBER ◽  
R. OSCHMANN ◽  
H.P. MERKLE ◽  
...  
Keyword(s):  
Brush Border ◽  
Enzymatic Cleavage ◽  
Brush Border Enzymes ◽  
Intestinal Brush Border ◽  
Intestinal Brush Border Enzymes

scholarly journals Comparison of the Susceptibilities of C57BL/6 and A/J Mouse Strains to Streptococcus suis Serotype 2 Infection

2008 ◽  
Vol 76 (9) ◽  
pp. 3901-3910 ◽  
Author(s):  
María de la Cruz Domínguez-Punaro ◽  
Mariela Segura ◽  
Danuta Radzioch ◽  
Serge Rivest ◽  
Marcelo Gottschalk
Keyword(s):  
Septic Shock ◽  
Inbred Mice ◽  
Late Phase ◽  
Streptococcus Suis ◽  
Mouse Strains ◽  
Necrosis Factor Alpha ◽  
Central Nervous System Damage ◽  
Proinflammatory Mediators ◽  
Outbred Mice

ABSTRACT Streptococcus suis is an important swine and human pathogen. Assessment of susceptibility to S. suis using animal models has been limited to monitoring mortality rates. We recently developed a hematogenous model of S. suis infection in adult CD1 outbred mice to study the in vivo development of an early septic shock-like syndrome that leads to death and a late phase that clearly induces central nervous system damage, including meningitis. In the present study, we compared the severities of septic shock-like syndrome caused by S. suis between adult C57BL/6J (B6) and A/J inbred mice. Clinical parameters, proinflammatory mediators, and bacterial clearance were measured to dissect potential immune factors associated with genetic susceptibility to S. suis infection. Results showed that A/J mice were significantly more susceptible than B6 mice to S. suis infection, especially during the acute septic phase of infection (100% of A/J and 16% of B6 mice died before 24 h postinfection). The greater susceptibility of A/J mice was associated with an exaggerated inflammatory response, as indicated by their higher production of tumor necrosis factor alpha, interleukin-12p40/p70 (IL-12p40/p70), gamma interferon, and IL-1β, but not with different bacterial loads in the blood. In addition, IL-10 was shown to be responsible, at least in part, for the higher survival in B6 mice. Our findings demonstrate that A/J mice are very susceptible to S. suis infection and provide evidence that the balance between pro- and anti-inflammatory mediators is crucial for host survival during the septic phase.

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