Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitrogen is one of the crucial elements that regulate plant growth and development. It is well-established that plants can acquire nitrogen from soil in the form of low-molecular-mass compounds, namely nitrate and ammonium, but also as amino acids. Nevertheless, nitrogen in the soil occurs mainly as proteins or proteins complexed with other organic compounds. Proteins are believed not to be available to plants. However, there is increasing evidence to suggest that plants can actively participate in proteolysis by exudation of proteases by roots and can obtain nitrogen from digested proteins. To gain insight into the process of organic nitrogen acquisition from proteins by leek roots (Allium porrum L. cv. Bartek), casein, bovine serum albumin and oxidized B-chain of insulin were used; their degradation products, after exposure to plant culture medium, were studied using liquid chromatography-mass spectrometry (LC-MS). Casein was degraded to a great extent, but the level of degradation of bovine serum albumin and the B-chain of insulin was lower. Proteases exuded by roots cleaved proteins, releasing low-molecular-mass peptides that can be taken up by roots. Various peptide fragments produced by digestion of the oxidized B-chain of insulin suggested that endopeptidase, but also exopeptidase activity was present. After identification, proteases were similar to cysteine protease from Arabidopsis thaliana. In conclusion, proteases exuded by roots may have great potential in the plant nitrogen nutrition.
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PMID:Degradation of proteins by enzymes exuded by Allium porrum roots - a potentially important strategy for acquiring organic nitrogen by plants. 1954 Jul 70

1. embranous nephropathy is characterized by an accumulation of immune deposits on the outer aspect of the glomerular basement membrane. 2. In the rat model described by Heymann in 1959, the target antigen of antibodies is megalin, a multiligand receptor expressed in the rat glomerulus but absent from the human glomerulus. 3. In recent years, two major antigens have been identified in human membranous nephropathy (MN). The first is neutral endopeptidase (NEP), the alloantigen involved in neonatal cases of MN that occur in newborns from NEP-deficient mothers. The second is the M-type phospholipase A(2) receptor (PLA(2) R), the first autoantigen identified in idiopathic MN in the adult. Megalin, NEP and PLA(2) R are all expressed on the podocyte surface, where they can serve as targets for circulating antibodies, leading to in situ immune complex formation, complement activation and proteinuria. 4. In addition to podocyte antigens, we recently showed that some patients with childhood MN had both circulating cationic bovine serum albumin (BSA) and anti-BSA antibodies, with BSA being present in immune deposits. This suggests that food antigens may be involved in MN through charge-dependent binding to the anionic glomerular capillary wall and in situ formation of immune complexes.
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PMID:Advances in membranous nephropathy: success stories of a long journey. 2138 32

Matrix metalloproteinase-2 (MMP-2) is an endopeptidase that has been shown to be present in high concentrations during most tissue remodeling events, including disease states like active tumor sites, thus making it an attractive molecule for use in effecting local delivery of therapeutic molecules. Moreover, the use of non-toxic and biodegradable nanoparticles for controlled drug delivery is highly sought after. To this end, bovine serum albumin (BSA) nanoparticles (NPs) were stabilized with coatings formed using domains of varying sensitivity to MMP-2, viz. K6GPQG/IASQK6 and K6HPVG/LLARK6, lysine residues being used to facilitate peptide immobilization to the BSA NPs via electrostatic interactions, and peptide domains that have a high (HPVG/LLAR) and low (GPQG/IASQ) MMP-2 cleavage rate. The MMP-2-induced cleavage rates of these two domains (the position of action being noted with a "/") have differing kinetics that can be used to provide a novel mechanism for facilitating the controlled release of molecules where local concentrations of MMP-2 are high. It was found that both surface concentration and cleavage domain type influenced the release of the model drug (BSA) from these NPs. This stratagem may provide a novel pathway for developing multi-functional coatings for controlling the local delivery of therapeutics at sites where the presence of various enzymes exist as a function of tissue state.
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PMID:Engineered peptides with enzymatically cleavable domains for controlling the release of model protein drug from "soft" nanoparticles. 2206 19

Antibodies to neutral endopeptidase, a podocyte protein, are responsible for rare alloimmune neonatal membranous nephropathy that develops in children from neutral endopeptidase-deficient mothers. Neutral endopeptidase was the first podocyte antigen described in human membranous nephropathy. PLA2R1, the type-M receptor of soluble phospholipase A2, is a major target antigen in so-called idiopathic membranous nephropathy in adults. Antibodies to PLA2R1 are detected in 60 to 80% of patients before immunosuppressive treatment, and are only occasionally found in secondary membranous nephropathy. To date, they have not been detected in other pathological conditions and in healthy individuals. PLA2R1 and HLA-DQA1 gene variants defined by single nucleotide polymorphisms are strongly associated with idiopathic membranous nephropathy in patients of white ancestry, and can thus be considered as predisposing genes. In addition to their diagnostic value, anti-PLA2R1 antibodies can be used to monitor treatment. Immunization against cationic bovine serum albumin is a cause of early childhood membranous nephropathy. This finding points to a possible role of food and environmental antigens in membranous nephropathy. The newly identified antigen-antibody systems should be considered as molecular signatures challenging the uniform histological definition and having a major impact on patient care in a near future.
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PMID:[Idiopathic and secondary membranous nephropathies]. 2220 61

Over the past few years, considerable advances have been made in our understanding of the molecular pathomechanisms of human membranous nephropathy, inspired by studies of Heymann nephritis, a faithful experimental model of this disease. This research led to the identification of neutral endopeptidase, the M-type receptor for secretory phospholipase A(2) (PLA(2)R1) and cationic bovine serum albumin as target antigens of circulating and deposited antibodies in alloimmune neonatal, adult 'idiopathic' and early-childhood membranous nephropathy, respectively. A genome-wide association study has provided further evidence for a highly significant association between PLA2R1 and HLA-DQA1 loci and idiopathic membranous nephropathy in patients of white ancestry. Additional antibody specificities for cytoplasmic antigens have also been identified, but their pathogenic role is uncertain. The time has come to revisit the spectrum of membranous nephropathies based on the newly identified antigen-antibody systems that should be considered as molecular signatures of the disease and that challenge the uniform histological definition. These signatures will soon have a major impact on patient care.
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PMID:Pathogenesis of membranous nephropathy: recent advances and future challenges. 2237 Dec 47

Botulinum neurotoxins are one of the most potent toxins known to man. Current methods of detection involve the quantification of the toxin but do not take into account the percentage of the toxin that is active. At present the assay used for monitoring the activity of the toxin is the mouse bioassay, which is lengthy and has ethical issues due to the use of live animals. This report demonstrates a novel assay that utilises the endopeptidase activity of the toxin to detect Botulinum neurotoxin in a pharmaceutical sample. The cleaving of SNAP-25 is monitored via UV-Visible spectroscopy with a limit of detection of 373 fg/mL and has been further developed into a high throughput method using a microplate reader detecting down to 600 fg/mL of active toxin. The results show clear differences between the toxin product and the placebo, which contains the pharmaceutical excipients human serum albumin and lactose, showing that the assay detects the active form of the toxin.
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PMID:A label free colorimetric assay for the detection of active botulinum neurotoxin type A by SNAP-25 conjugated colloidal gold. 2392 42

In this article, we report the intrinsic catalytic activity of graphene oxide (GO) for the nonspecific cleavage of proteins. We used bovine serum albumin (BSA) and a recombinant esterase (rEstKp) from the cold-adapted bacterium Pseudomonas mandelii as test proteins. Cleavage of BSA and rEstKp was nonspecific regarding amino acid sequence, but it exhibited dependence on temperature, time, and the amount of GO. However, cleavage of the proteins did not result in complete hydrolysis into their constituent amino acids. GO also invoked hydrolysis of p-nitrophenyl esters at moderate temperatures lower than those required for peptide hydrolysis regardless of chain length of the fatty acyl esters. Based on the results, the functional groups of GO, including alcohols, phenols, and carboxylates, can be considered as crucial roles in the GO-mediated hydrolysis of peptides and esters via general acid-base catalysis. Our findings provide novel insights into the role of GO as a carbocatalyst with nonspecific endopeptidase activity in biochemical reactions.
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PMID:Nonspecific cleavage of proteins using graphene oxide. 2450 87

Membranous nephropathy (MN) is a kidney disease characterized by deposition of immune complexes and complement on the outer aspect of the glomerular capillary wall. It is responsible for a loss of serum proteins in the urine and kidney failure. During the last ten years, considerable progress has occurred in the understanding of the molecular bases of the disease with the description of three distinct mechanisms in humans. In the neonatal allo-immune form, antibodies are directed against neutral endopeptidase (NEP), a podocyte antigen absent in the mothers who become immunized against this antigen expressed by placenta cells during pregnancy. NEP was the first podocyte antigen to be identified in MN. Most adult forms of MN are autoimmune diseases without identified etiology (primary MN), linked to the production of antibodies raised against another podocyte antigen, the type-M phospholipase A2 receptor (PLA2R1). Anti-PLA2R1 antibodies are detected in 70 to 80% of patients before any immunosuppressive treatment, and only occasionally in secondary forms of MN, variants of PLAR1 and HLA-DQA1 genes are very significantly associated with occurrence of primary MN in Caucasians. The third mechanism is characterized by immunization against a foreign protein, cationic bovine serum albumin (BSA), which is involved in rare forms of MN during early childhood. This finding points to a possible role of food and environmental antigens in membranous nephropathy.
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PMID:[Pathophysiology of extramembranous glomerulopathies. Fifty years of progress, from laboratory to patient]. 2459 73

Since the early 2000s, considerable advances have been achieved in the understanding of molecular pathomechanisms of human membranous nephropathy (MN), inspired by studies of Heymann nephritis, a faithful experimental model. These studies led to the identification of neutral endopeptidase, the type-M phospholipase A2 receptor (PLA2R), and cationic bovine serum albumin as target antigens of circulating and deposited antibodies in neonatal alloimmune, adult 'idiopathic', and early childhood MN, respectively. A genome-wide association study further showed a highly significant association of the PLA2R1 and the HLA-DQA1 loci with idiopathic MN in patients of white ancestry. The time has come to revisit the spectrum of MN based on the newly identified antigen-antibody systems which should be considered as molecular signatures of the disease, challenging the uniform histological definition. Although some uncertainties remain as to the pathogenic effects of anti-PLA2R antibodies because of the lack of an appropriate experimental model, the value of these antibodies as biomarkers for diagnosis and disease activity is increasingly being recognized. It is not exaggerated to state that they have induced a paradigm shift in the monitoring of patients with MN, thus opening a new era of personalized medicine.
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PMID:Anti-phospholipase A2 receptor antibodies and the pathogenesis of membranous nephropathy. 2540 74

Angioimmunoblastic T-cell lymphoma (AITL) is a distinct peripheral T-cell lymphoma entity exhibiting peculiar clinical features and poor prognosis. Its clinical characteristics and prognostic factors are not well established. To clarify the clinical characteristics and prognostic features of AITL, we conducted a multicenter, retrospective study. Fifty-six patients were enrolled. The median patient age was 68 years. Immunohistochemical examinations of tumor cells showed positivity for CD10 and T-cell markers, and chromosomal examination detected several types of abnormalities. More than 80 % of patients show advanced disease at diagnosis and poor prognostic scores. A high proportion of patients showed accompanying B symptoms, splenomegaly, and hepatomegaly at diagnosis. The 5-year overall survival (OS) rate was 48 % and progression-free survival was 25 %. Univariate analysis revealed higher age, fever, poor performance status, anemia, and low albumin level to be poor prognostic factors for OS. In addition to these factors, both IPI and PIT were also predictive of OS. Multivariate analysis indicated only a low level of serum albumin to be a significant prognostic factor for OS. Serum albumin may be one of the important prognostic factors for AITL. Further investigation is needed to confirm these results.
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PMID:Analysis of clinical characteristics and prognostic factors for angioimmunoblastic T-cell lymphoma. 2573 82


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