Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of ozone on human alpha 1-proteinase inhibitor (A-1-PI), alpha 1-antichymotrypsin (A-1-Achy), bronchial leukocyte proteinase inhibitor (BLPI), and Eglin C were studied using in vitro exposures in phosphate-buffered solutions. Following ozone exposure, inhibitory activities against human neutrophil elastase (HNE) and/or cathepsin G (Cat G) were measured. Exposure of A-1-PI to 50 mol O3/mol protein resulted in a complete loss of HNE inhibitory activity, whereas A-1-Achy lost only 50% of its Cat G inhibitory activity and remained half active even after exposure to 250 mol of O3. At 40 mol O3/mol protein, BLPI lost 79% of its activity against HNE and 87% of its Cat G inhibitory activity. Eglin C, a leech-derived inhibitor, lost 81% of its HNE inhibitory activity and 92% of its ability to inhibit Cat G when exposed to 40 mol O3/mol. Amino acid analyses of ozone-exposed inhibitors showed destruction of Trp, Met, Tyr, and His with as little as 10 mol O3/mol protein, and higher levels of O3 resulted in more extensive oxidation of susceptible residues. The variable ozone susceptibility of the different amino acid residues in the four proteins indicated that oxidation was a function of protein structure, as well as the inherent susceptibility of particular amino acids. Exposure of A-1-PI and BLPI in the presence of the antioxidants, Trolox C (water soluble vitamin E) and ascorbic acid (vitamin C), showed that antioxidant vitamins may protect proteins from oxidative inactivation by ozone. Methionine-specific modification of BLPI reduced its HNE and Cat G inhibitory activities. Two moles of N-chlorosuccinimide per mole of BLPI methionine caused an 80% reduction in activity against Cat G, but only a 40% reduction in HNE inhibitory activity.
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PMID:Ozone effects on inhibitors of human neutrophil proteinases. 349 63

Thrombospondin 1 is a multidomain trimeric glycoprotein from platelets and a variety of normal and transformed cells of both mesenchymal and epithelial origin, which functions in cell adhesion and cell-cell interactions. We have recently shown that human thrombospondin 1 binds and inhibits the neutrophil enzymes, neutrophil elastase [Hogg, P.J., Owensby, D.A., Mosher, D.F., Misenheimer, T.M., & Chesterman, C.N. (1993a) J. Biol. Chem. 268, 7139-7146] and cathepsin G [Hogg, P.J., Owensby, D.A., & Chesterman, C.N. (1993b) J. Biol. Chem. 268, 21811-21818]. One mole of thrombospondin 1 trimer binds 3 mol of neutrophil elastase or up to 6 mol of cathepsin G, with site-binding dissociation constants around the nanomolar range, and the enzymes have been shown to interact with thrombospondin 1 in the vicinity of the calcium-binding type 3 repeats. None of the protein modules in this region, or within the whole thrombospondin 1 molecule, have previously been implicated in the inhibition of proteinases. We noted that there are two stretches of eight amino acids each in the human thrombospondin 1 type 3 repeats, residues 735-742 and 794-801, that have striking similarity to a reactive-site consensus sequence derived from selected members of the Kazal and Streptomyces subtilisin inhibitor families. Synthetic peptides corresponding to the putative P5 through P4' residues of both proposed reactive centers interacted efficiently with the active site of cathepsin G and were competitive inhibitors of the fibronectin-degrading and platelet-activating activities of this enzyme, while only the peptide corresponding to residues 793-801 efficiently interacted with the active site of neutrophil elastase and competitively inhibited its fibronectin-degrading activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of possible inhibitory reactive centers in thrombospondin 1 that may bind cathepsin G and neutrophil elastase. 820 88

High elastase and cathepsin G activities have been observed in chronic wounds to inhibit healing through degradation of growth factors, cytokines, and extracellular matrix proteins. Oleic acid is a non-toxic elastase inhibitor. Cotton wound dressing material was characterized as a transfer carrier for affinity uptake of oleic acid by albumin under conditions mimicking chronic wounds. The mechanism of oleic acid uptake from cotton and binding by albumin was examined with both intact dressings and cotton fiber-designed chromatography. Raman spectra of the albumin-oleic acid complexes under liquid equilibrium conditions revealed fully saturated albumin-oleic acid complexes with a 1:1 weight ratio of albumin:oleic acid. Liquid-solid equilibrium conditions revealed oleic acid transfer from cotton to albumin at 27 mole equivalents of oleic acid per mole albumin. Comparing oleic acid formulated wound dressings for dose dependent ability to lower elastase activity, we found cotton gauze>hydrogel>hydrocolloid. In contrast, the cationic serine protease cathepsin G was inhibited by oleic acid within a narrow range of oleic acid-cotton formulations. 2% albumin was sufficient to transfer quantities of oleic acid necessary to achieve a significant elastase-lowering effect. Oleic acid bound to cotton wound dressings may have promise in the selective lowering of cationic serine protease activity useful in topical application for chronic inflammatory pathogenesis.
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PMID:Protease inhibition by oleic acid transfer from chronic wound dressings to albumin. 1757 Jun 26