Ozone-induced oxidative modification of plasma fibrin-stabilizing factor.
The plasma fibrin-stabilizing factor (pFXIII) function is to maintain a hemostasis by the fibrin clot stabilization. The conversion of pFXIII to the active form of the enzyme (FXIIIа) is a multistage process. Ozone-induced oxidation of pFXIII has been investigated at different stages of its enzyme activation. The biochemical results point to a decrease of an enzymatic activity of FXIIIа depending largely on the stage of the pFXIII conversion into FXIIIа at which oxidation was carried out. UV-, FTIR- and Raman spectroscopy demonstrated that chemical transformation of cyclic, NH, SH and S-S groups mainly determines the oxidation of amino acid residues of pFXIII polypeptide chains. Conversion of pFXIII to FXIIIa proved to increase protein sensitivity to oxidation in the order: pFXIII<pFXIII activated by thrombin<pFXIII in the presence of calcium ions<FXIIIa. The dynamic light scattering data indicate that the three-dimensional structure of pFXIII becomes loosened due to oxidative modification. ESR spectroscopy data also point to conformational changes of the fibrin-stabilizing factor under oxidation. Taking into account these new findings it seems reasonable to assume that the inhibitory/carrier FXIII-B subunits can serve as scavengers of ROS. Hypothetically, this mechanism could help to protect the key amino acid residues of the FXIII-A subunits responsible for the enzymatic function of FXIIIa.
N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 4, Kosygina str., 119334 Moscow, Russia. Electronic address: markrosenfeld@rambler.ru.
Mark A
MA
Rosenfeld
Anna V
AV
Bychkova
Alexander N
AN
Shchegolikhin
Vera B
VB
Leonova
Marina I
MI
Biryukova
Elizaveta A
EA
Kostanova
D026122:Factor XIIIa / Q000737:chemistry* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000737:chemistry* / Q000378:metabolism; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D010083:Oxidants, Photochemical / Q000737:chemistry*; D010084:Oxidation-Reduction; D010126:Ozone / Q000737:chemistry*
D016166:Free Radical Scavengers; D005609:Free Radicals; D010083:Oxidants, Photochemical; D010126:Ozone; D026122:Factor XIIIa
Chemical transformation; Oxidation; Plasma factor XIII; Plasma factor XIII activation; Structure