TY - JOUR AU - Ádány, Róza AU - Bárdos, Helga AU - Antal, Miklós AU - Módis, László AU - Sárváry, Attila AU - Szűcs, Sándor AU - Balogh, I TI - Factor XIII of blood coagulation as a nuclear crosslinking enzyme JF - THROMBOSIS AND HAEMOSTASIS J2 - THROMB HAEMOSTASIS VL - 85 PY - 2001 IS - 5 SP - 845 EP - 851 PG - 7 SN - 0340-6245 DO - 10.1055/s-0037-1615758 UR - https://m2.mtmt.hu/api/publication/5175 ID - 5175 N1 - Megjegyzés-21289832 Chemicals/CAS: Cross-Linking Reagents; Factor XIII, 9013-56-3; Factor XIIIa, EC 2.3.2.13; Glutaral, 111-30-8; Immune Sera AB - Intracellular localization and distribution of Factor XIII subunit A (FXIIIA) was investigated in association with monocyte-macrophage differentiation in a long term culture of human monocytes by light- and electron microscopical as well as biochemical and immunobiochemical techniques. To allow the detection of FXIIIA in cells with well-preserved ultrustructure, immunosera against glutaraldehyde-derivatized recombinant FXIIIA were developed in rabbits, then characterized and used in this study. In the early phase of macrophage differentiation intranuclear accumulation of FXIIIA was detected as a transient phenomenon in cells of the 2nd day culture by optical sectioning with 0,7 microm steps in laser scanning confocal microscopy and immunoblotting technique. FXIIIA could be detected by immunoelectron microscopic postembedding staining over electrodense DNA-containing areas. Fluoresceinated monodansylcadaverine incorporation assay was used to demonstrate that FXIIIA is not only present in the nuclei, but also expresses its transglutaminase activity. Our finding of the nuclear accumulation of FXIIIA in differentiating human macrophages is also unique in that a blood clotting factor has, for the first time, been localized in nuclei and has been shown to be an intracellular crosslinking enzyme. The possible role of nuclear FXIIIA in association with cellular processes involving chromatin structure remodeling, such as cell death, cell differentiation or cellular proliferation requires further in-depth investigation. LA - English DB - MTMT ER - TY - JOUR AU - Muszbek, László AU - Haramura, G AU - Polgar, J TI - Transformation of Cellular Factor XIII Into An Active Zymogen Transglutaminase In Thrombin-stimulated Platelets JF - THROMBOSIS AND HAEMOSTASIS J2 - THROMB HAEMOSTASIS VL - 73 PY - 1995 IS - 4 SP - 702 EP - 705 PG - 4 SN - 0340-6245 UR - https://m2.mtmt.hu/api/publication/1095994 ID - 1095994 N1 - Debrecen Univ Sch Med, Dept Clin Chem, H-4012 Debrecen, Hungary AB - The cellular form of blood coagulation factor XIII (FXIII) is present in platelets, monocytes and macrophages. During long-term stimulation of platelets by thrombin cellular FXIII becomes activated and crosslinks proteins, however, the mechanism of its activation has not been elucidated. It was shown that, contrary to plasma FXIII, the intracellular activation of platelet FXIII does not involve proteolysis. FXIII remained intact in thrombin-activated platelets, i.e., the activation peptide was not removed from the molecule. Part of the zymogen FXIII molecules, however, assumed an active configuration as was demonstrated both by the measurement of transglutaminase activity and by active-site-SH titration. These findings clearly indicate that during platelet activation, when intracellular Ca2+ concentration is raised, a slow non-proteolytic transformation of FXIII zymogen into an active transglutaminase occurs LA - English DB - MTMT ER - TY - JOUR AU - Muszbek, László AU - Polgar, J AU - Boda, Zoltán TI - Platelet Factor XIII Becomes Active Without The Release of Activation Peptide During Platelet Activation JF - THROMBOSIS AND HAEMOSTASIS J2 - THROMB HAEMOSTASIS VL - 69 PY - 1993 IS - 3 SP - 282 EP - 285 PG - 4 SN - 0340-6245 UR - https://m2.mtmt.hu/api/publication/1095986 ID - 1095986 N1 - DEBRECEN UNIV SCH MED, DEPT CLIN CHEM, DEPT MED 2, H-4012 DEBRECEN, HUNGARY. AB - The potentially active A subunit of factor XIII of blood coagulation has also been detected in platelets and monocytes/macrophages though the exact function of this cellular protransglutaminase has not yet been elucidated. In physiological conditions the first step in the activation of plasma factor XIII is the removal of an activation peptide from the N-terminal end of subunit A by thrombin. The A subunit then, in the presence of Ca2+, dissociates from the inhibitory B subunit and assumes an active conformation. Cellular factor XIII, which lacks B subunit, can be proteolytically activated in vitro by thrombin and the intracellular Ca2+ sensitive protease, calpain, in the same way as plasma factor XIII subunit A, and calpain has been suggested as the intracellular protease involved in the activation of cellular factor XIII in platelets. In the present experiments it was shown by SDS PAGE that during long-term stimulation of platelets with thrombin nondisulfide-crosslinked high M(r) protein polymers not penetrating the concentrating gel were formed. The lack of these polymers in thrombin-stimulated factor XIII deficient platelets clearly indicated that their formation in normal platelets was due to factor XIII that became active during platelet activation. However, no release of the activation peptide could be detected by Western blotting during this process. Similarly, no proteolytic cleavage of factor XIII was detectable when platelets were stimulated by Ca2+ ionophore through this stimulus activated calpain as it was clearly demonstrated by the breakdown of major intracellular calpain substrates. The results indicate: 1) during thrombin induced platelet activation factor XIII becomes active and crosslinks platelet protein, 2) platelet factor XIII is not an intracellular substrate of calpain, 3) cellular factor XIII could be activated without the proteolytic removal of activation peptide. It is presumed that the nonproteolytic pathway for the activation of cellular factor XIII, we reported most recently, might have physiological implications under such conditions. LA - English DB - MTMT ER - TY - JOUR AU - Fésüs, László TI - Apoptosis fashions T and B cell repertoire JF - IMMUNOLOGY LETTERS J2 - IMMUNOL LETT VL - 30 PY - 1991 IS - 3 SP - 277 EP - 282 PG - 6 SN - 0165-2478 DO - 10.1016/0165-2478(91)90038-C UR - https://m2.mtmt.hu/api/publication/1102034 ID - 1102034 LA - English DB - MTMT ER - TY - JOUR AU - Hársfalvi, Jolán AU - Fésüs, László AU - Tarcsa, E AU - Laczko, J AU - Loewy, A TI - The presence of covalently cross-lined matrix in human platelets JF - BIOCHIMICA ET BIOPHYSICA ACTA J2 - BIOCHIM BIOPHYS ACTA VL - 1073 PY - 1991 SP - 268 EP - 274 PG - 7 SN - 0006-3002 DO - 10.1016/0304-4165(91)90131-Y UR - https://m2.mtmt.hu/api/publication/1102037 ID - 1102037 AB - Exhaustive extraction of human platelets with 6 M guanidine-HCl, and 5% beta-mercaptoethanol, followed by 5% SDS resulted in a sedimentable material which showed fibrous structure by transmission electron microscopy. When platelets treated with 8 M urea, 50 mM DTT and 2% SDS were applied on a 3% solubilizable acrylamide gel a high molecular weight material could be also isolated which was highly crosslinked by epsilon(gamma-glutamyl)lysine bonds. Its amino acid composition was Asp 110, Glu 119, Ser 55, Gly 70, Arg 33, Thr 41, Ala 112, Pro 93, Tyr 35, Val 18, Met 55, Cys 46, IIe 47, Leu 71, Phe 27, Lys 76 expressed as residue per 1000. The quantity of platelet polymer material as well as the amount of epsilon(gamma-glutamyl)lysine bond was slightly higher in thrombin activated platelets. The insoluble matrix of resting platelets reacts with antibodies against spectrin, alpha-actinin, actin, myosin, tropomyosin. The matrix from activated platelets has shown reaction with additional antibodies including ones against blood coagulation factor XIIIa, fibrinogen, von Willebrand factor, thrombospondin, tubulin and filamin. The presence of an epsilon(gamma-glutamyl)lysine cross-linked cell matrix in platelets is consistent with the observation of a similar structure in other cells. LA - English DB - MTMT ER - TY - JOUR AU - Polgar, J AU - Hidasi, Vanda AU - Muszbek, László TI - Non-Proteolytic Activation of Cellular Protransglutaminase (Placenta Macrophage Factor-XIII) JF - BIOCHEMICAL JOURNAL J2 - BIOCHEM J VL - 267 PY - 1990 IS - 2 SP - 557 EP - 560 PG - 4 SN - 0264-6021 DO - 10.1042/bj2670557 UR - https://m2.mtmt.hu/api/publication/1095973 ID - 1095973 N1 - DEBRECEN UNIV SCH MED,DEPT CLIN CHEM,POB 40,H-4012 DEBRECEN,HUNGARY. LA - English DB - MTMT ER - TY - JOUR AU - Asijee, GM AU - Muszbek, László AU - Kappelmayer, János AU - Polgar, J AU - Horváth, Andrea Rita AU - Sturk, A TI - Platelet Vinculin - A Substrate of Activated Factor-XIII JF - BIOCHIMICA ET BIOPHYSICA ACTA J2 - BIOCHIM BIOPHYS ACTA VL - 954 PY - 1988 IS - 3 SP - 303 EP - 308 PG - 6 SN - 0006-3002 DO - 10.1016/0167-4838(88)90085-4 UR - https://m2.mtmt.hu/api/publication/1095962 ID - 1095962 LA - English DB - MTMT ER -