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Tytuł artykułu

Properties of chemically oxidized kininogens

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
Kininogens are multifunctional proteins involved in a variety of regulatory pro­cesses including the kinin-formation cascade, blood coagulation, fibrynolysis, inhibi­tion of cysteine proteinases etc. A working hypothesis of this work was that the prop­erties of kininogens may be altered by oxidation of their methionine residues by reac­tive oxygen species that are released at the inflammatory foci during phagocytosis of pathogen particles by recruited neutrophil cells. Two methionine-specific oxidizing reagents, .-chlorosuccinimide (NCS) and chloramine-T (CT), were used to oxidize the high molecular mass (HK) and low molecular mass (LK) forms of human kininogen. A nearly complete conversion of methionine residues to methionine sulfoxide residues in the modified proteins was determined by amino acid analysis. Production of kinins from oxidized kininogens by plasma and tissue kallikreins was significantly lower (by at least 70%) than that from native kininogens. This quenching effect on kinin release could primarily be assigned to the modification of the critical Met-361 residue adja­cent to the internal kinin sequence in kininogen. However, virtually no kinin could be formed by human plasma kallikrein from NCS-modified HK. This observation sug­gests involvement of other structural effects detrimental for kinin production. In­deed, NCS-oxidized HK was unable to bind (pre)kallikrein, probably due to the modifi­cation of methionine and/or tryptophan residues at the region on the kininogen mole­cule responsible for the (pro)enzyme binding. Tests on papain inhibition by native and oxidized kininogens indicated that the inhibitory activity of kininogens against cysteine proteinases is essentially insensitive to oxidation.

Wydawca

-

Rocznik

Tom

50

Numer

3

Opis fizyczny

p.753-763,fig.

Twórcy

autor
  • Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland
autor
autor
autor
autor

Bibliografia

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Bibliografia

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