			Home About us Contact

Elastase Inhibitor (elastase + inhibitor)

Distribution by Scientific Domains

Medical Sciences	60%

Selected Abstracts

Neutrophil elastase in pressure ulcer fluid degrades fibronectin in the exudates

GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 3 2004
Shingo Ai
Background: Pressure ulcers are classified as chronic wounds, which do not heal in a timely fashion. Fibronectin is condensed in granulation tissue, and essential glycoprotein of wound healing. It has been proposed that fibronectin degradation may be involved in delaying wound healing. We have investigated whether pressure ulcer fluid (PUF) contains degraded fibronectin. In addition, we tried to identify the proteinase which contributes to fibronectin degradation in PUF. Methods: Fibronectin degradation and the presence of neutrophil elastase (NE) in PUF were determined by immunoblot analysis. Fibronectin degradation activity in PUF was determined in the presence of various proteinase inhibitors. NE activity was assessed using NE specific substrate. Results: Immunoblot analysis revealed that degraded fibronectin was observed in PUF samples but not in acute wound fluid (AWF). The PUF contained a proteinase capable of degrading freshly added fibronectin and its activity in PUF was blocked by a broad-spectrum serine proteinase inhibitor or sivelestat, a specific neutrophil elastase inhibitor, but not by metalloproteinase and cysteine proteinase inhibitors. Immunoblot analysis of PUF using an antineutrophil elastase antibody revealed that neutrophil elastase was detected as three bands at molecular weights of ,30 kDa, ,38 kDa, and ,54 kDa, indicating that neutrophil elastase in the exudates existed not only as free monomers, but also in polymers or complexes with other molecules. Conclusion: These results suggest that PUF contains a high level of neutrophil elastase which may be involved in the delay of the healing of pressure ulcer through the fibronectin degradation. [source]

Activity-based mass spectrometric characterization of proteases and inhibitors in human saliva

PROTEOMICS - CLINICAL APPLICATIONS, Issue 7 2009
Xiuli Sun
Abstract Proteases present in oral fluid effectively modulate the structure and function of some salivary proteins and have been implicated in tissue destruction in oral disease. To identify the proteases operating in the oral environment, proteins in pooled whole saliva supernatant were separated by anion-exchange chromatography and individual fractions were analyzed for proteolytic activity by zymography using salivary histatins as the enzyme substrates. Protein bands displaying proteolytic activity were particularly prominent in the 50,75,kDa region. Individual bands were excised, in-gel trypsinized and subjected to LC/ESI-MS/MS. The data obtained were searched against human, oral microbial and protease databases. A total of 13 proteases were identified all of which were of mammalian origin. Proteases detected in multiple fractions with cleavage specificities toward arginine and lysine residues, were lactotransferrin, kallikrein-1, and human airway trypsin-like protease. Unexpectedly, ten protease inhibitors were co-identified suggesting they were associated with the proteases in the same fractions. The inhibitors found most frequently were alpha-2-macroglobulin-like protein 1, alpha-1-antitrypsin, and leukocyte elastase inhibitor. Regulation of oral fluid proteolysis is highly important given that an inbalance in such activities has been correlated to a variety of pathological conditions including oral cancer. [source]

Neutrophil elastase inhibitor prevents endotoxin-induced liver injury following experimental partial hepatectomy (Br J Surg 2007; 94: 609,619)

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2007
T. Fujita
No abstract is available for this article. [source]

Caspase 1,independent activation of interleukin-1, in neutrophil-predominant inflammation

ARTHRITIS & RHEUMATISM, Issue 12 2009
Monica Guma
Objective Interleukin-1, (IL-1,) is a key cytokine linked to the pathogenesis of acute arthritis. Caspase 1, neutrophil elastase, and chymase all process proIL-1, to its biologically active form. This study was undertaken to examine the potential contributions of each of these proteases in experimental models of inflammatory arthritis. Methods Caspase 1,deficient (Casp1,/,) and wild-type (WT) mice were tested for their response to arthritogenic K/BxN serum transfer for induction of arthritis or injection of monosodium urate monohydrate (MSU) crystals for induction of peritonitis. All mice were prophylactically treated with inhibitors of neutrophil elastase or chymase. Arthritic paws were tested for the presence of IL-1, protein by enzyme-linked immunosorbent assay and Western blotting. Neutrophils and mast cells from WT and mutant mice were tested for their ability to secrete IL-1, after in vitro stimulation, in the presence of protease inhibitors. Results Casp1,/, and WT mice developed paw swelling to the same extent in the K/BxN serum transfer,induced arthritis model. MSU crystal injection into Casp1,/, mice also resulted in neutrophil influx and production of measurable peritoneal IL-1, protein. Both of these responses were attenuated with neutrophil elastase inhibitors. K/BxN serum transfer,induced arthritis was also reduced by treatment with a chymase inhibitor. Casp1,/, neutrophils and mast cells, when exposed to MSU crystals, secreted similar amounts of IL-1, protein upon in vitro stimulation with lipopolysaccharide, albeit at lower levels than that secreted by WT cells. Elastase and chymase inhibitors reduced the amount of IL-1, released by these cells. Conclusion The production of IL-1, by neutrophils and mast cells is not exclusively dependent on caspase 1, and other proteases can compensate for the loss of caspase 1 in vivo. These pathways might therefore compromise the caspase 1,targeted therapies in neutrophil-predominant arthritis. [source]

Structure of the complex of porcine pancreatic elastase with a trimacrocyclic peptide inhibitor FR901451

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 9 2005
Takayoshi Kinoshita
Porcine pancreatic elastase (PPE) resembles the attractive drug target leukocyte elastase, which has the ability to degrade connective tissue in the body. The crystal structure of PPE complexed with a novel trimacrocyclic peptide inhibitor, FR901451, was solved at 1.9,Å resolution. The inhibitor occupied the subsites S3 through S3, of PPE and induced conformational changes in the side chains of Arg64 and Arg226, which are located at the edges of the substrate-binding cleft. Structural comparison of five PPE,inhibitor complexes, including the FR901451 complex and non-ligated PPE, reveals that the residues forming the S2, S1, S1, and S2, subsites in the cleft are rigid, but the two arginine residues playing a part in the S3 and S3, subsites are flexible. Structural comparison of PPE with human leukocyte elastase (HLE) implies that the inhibitor binds to HLE in a similar manner to the FR901451,PPE complex. This structural insight may help in the design of potent elastase inhibitors. [source]