Leukocyte-mediated inactivation of α1-proteinase inhibitor is inhibited by amino analogues of α-tocopherol
| Autor: | Frank Bolkenius |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Xanthine Oxidase
Tertiary amine Tocopherols Hypochlorite Exocytosis Superoxide dismutase Glucose Oxidase chemistry.chemical_compound Superoxides Leukocytes Humans Vitamin E NADH NADPH Oxidoreductases Hydrogen peroxide Molecular Biology Peroxidase NADPH oxidase Pancreatic Elastase biology Elastase Zymosan NADPH Oxidases Hydrogen Peroxide Cell Biology Biochemistry chemistry alpha 1-Antitrypsin Myeloperoxidase biology.protein |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1095:23-29 |
| ISSN: | 0167-4889 |
| Popis: | Human leukocytes stimulated by opsonized zymosan increase their NADPH oxidase-catalysed reduction of molecular oxygen. This leads to enhanced formation of superoxyl radicals and subsequently hydrogen peroxide. The leukocyte enzyme myeloperoxidase generates the strong microbicidal oxidant hypochlorite from hydrogen peroxide and chloride anions. Hypochlorite inactivates serum alpha 1-proteinase inhibitor, a protein which protects host tissue from digestion by proteinases, that are also secreted by stimulated leukocytes. Micromolar concentrations of a water-soluble, quaternary ammonium analogue of alpha-tocopherol (vitamin E) (3,4-dihydro-6-hydroxy-N,N,N-2,5,7,8-heptamethyl-2H-1-benzopyran-2 -ethanaminium 4-methylbenzenesulfonate) and its tertiary amine derivative (3,4-dihydro-2- (2-dimethylaminoethyl)-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol hydrochloride) were able to protect alpha 1-proteinase inhibitor from inactivation by stimulated human leukocytes. The mechanism of action of the quaternary ammonium analogue was further investigated. Selective inhibition of hydrogen peroxide formation is assumed to be the reason for its protective effect. This compound rapidly reacts with superoxyl radicals, but not with hydrogen peroxide, and is only a weak hypochlorite scavenger. It neither impedes exocytosis of elastase, nor effectively inhibits NADPH oxidase or myeloperoxidase. In contrast, superoxide dismutase, which enhances hydrogen peroxide formation, cannot protect alpha 1-proteinase inhibitor from inactivation. |
| Databáze: | OpenAIRE |
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