[Inactivation of blood plasma alpha 1-proteinase inhibitor as affected by 2 splenic thiol proteinases active in a neutral medium].
It has been found that two active in neutral medium thiol proteinases from bovine spleen, cathepsin L and cathepsin H, bring about rapid and irreversible inactivation of alpha 1-proteinase inhibitor (alpha 1PI)--one of the major plasma inhibitors of serine proteinases. The activity of the enzymes studied did not change upon the interaction with alpha 1PI. With stoichiometric proteinase/inhibitor ratio, the inactivation of alpha 1PI under the effect of cathepsin L was instantaneous, while under the effect of cathepsin H it occurred within 30-60 min. The products of alpha 1PI inactivation had an inhibitory effect on the rate of its reaction with cathepsin L. alpha 1PI inactivation under the action of cathepsin L and cathepsin H was accompanied by the decrease in the molecular mass of the inhibitor from 54 kDA to 46 kDa. This was, probably, caused by the hydrolysis of the peptide bond formed by NH2 group of threonine. The 46 kDa fragment did not undergo further degradation. It did not bind to immobilized trypsin but retained antigenic properties. The results obtained show that the limited proteolysis is a mechanism of the inhibitor inactivation. It is suggested that under some conditions thiol proteinases, upon their release from the cell, participate in the control of effective alpha 1PI concentration.
Lokshina
L A
LA
Golubeva
N V
NV
Baranova
F S
FS
Orekhovich
V N
VN
D000818:Animals; D001798:Blood Proteins / Q000037:antagonists & inhibitors*; D056655:Cathepsin H; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism; D002417:Cattle; D003546:Cysteine Endopeptidases; D004347:Drug Interactions; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D013154:Spleen / Q000201:enzymology*; D013997:Time Factors; D000515:alpha 1-Antitrypsin
D001798:Blood Proteins; D000515:alpha 1-Antitrypsin; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C534126:CTSH protein, human; D056655:Cathepsin H
Inaktivatsiia alfa 1-proteinaznogo ingibitora plazmy krovi pod deĭstviem dvukh aktivnykh v neĭtral'noĭ srede tiolovykh proteinaz selezenki.