Navegando por Palavras-chave "plasmin"

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    Activation profiles of human kallikrein-related peptidases by proteases of the thrombostasis axis
    (Cold Spring Harbor Lab Press, Publications Dept, 2008-11-01) Yoon, Hyesook; Blaber, Sachiko I.; Evans, D. Michael; Trim, Julie; Juliano, Maria Aparecida [UNIFESP]; Scarisbrick, Isobel A.; Blaber, Michael; Florida State Univ; Vantia Ltd; Ferring Res Ltd; Universidade Federal de São Paulo (UNIFESP); Mayo Med & Grad Sch
    The human kallikrein-related peptidases (KLKs) comprise 15 members (KLK1-15) and are the single largest family of serine proteases. the KLKs are utilized, or proposed, as clinically important biomarkers and therapeutic targets of interest in cancer and neurodegenerative disease. All KLKs appear to be secreted as inactive pro-forms (pro-KLKs) that are activated extracellularly by specific proteolytic release of their N-terminal pro-peptide. This processing is a key step in the regulation of KLK function. Much recent work has been devoted to elucidating the potential for activation cascades between members of the KLK family, with physiologically relevant KLK regulatory cascades now described in skin desquamation and semen liquefaction. Despite this expanding knowledge of KLK regulation, details regarding the potential for functional intersection of KLKs with other regulatory proteases are essentially unknown. To elucidate such interaction potential, we have characterized the ability of proteases associated with thrombostasis to hydrolyze the pro-peptide sequences of the KLK family using a previously described pro-KLK fusion protein system. A subset of positive hydrolysis results were subsequently quantified with proteolytic assays using intact recombinant pro-KLK proteins. Pro-KLK6 and 14 can be activated by both plasmin and uPA, with plasmin being the best activator of pro-KLK6 identified to date. Pro-KLK11 and 12 can be activated by a broad-spectrum of thrombostasis proteases, with thrombin exhibiting a high degree of selectivity for pro-KLK12. the results show that proteases of the thrombostasis family can efficiently activate specific pro-KLKs, demonstrating the potential for important regulatory interactions between these two major protease families.
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    Characterization of a Kunitz trypsin inhibitor with one disulfide bridge purified from Swartzia pickellii
    (Elsevier B.V., 2002-03-01) Cavalcanti, MDM; Oliva, MLV; Fritz, H.; Jochum, M.; Mentele, R.; Sampaio, M.; Coelho, LCBB; Batista, IFC; Sampaio, CAM; Universidade Federal de Pernambuco (UFPE); Univ Pernambuco; Universidade Federal de São Paulo (UNIFESP); Univ Munich
    Swartzia pickellii is a Leguminosae that belongs to the Caesalpinioideae sub-family the Swartzia pickellii Trypsin Inhibitor (SWTI), a serine proteinase inhibitor was isolated from its seeds. SWTI is a single polypeptide chain protein and it's structure has 174 amino acid residues, it homologous to other Kunitz plant inhibitors, however shows some major differences: it contains only one disulfide bridge, instead two which are usually found in plant Kunitz inhibitors, and the SWTI reactive site does not contain the usual Arg or Lys residues at the putative reactive site (position 65). A glycosylation site was detected at Asn38 with 1188 kDa carbohydrate portion. the primary structure micro heterogeneity was found combining the sequence determination and mass spectrometry. Three forms of SWTI were actually defined: two glycosylated forms a 20,204 kDa (Arg 165) and 20,185 kDa (His 165) and one deglycosylated form 19,016 kDa (Arg 165), all of them contain a Met residue at position 130. (C) 2002 Elsevier Science (USA).
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    Effect of invertebrate serine proteinase inhibitors on carrageenan-induced pleural exudation and bradykinin release
    (Elsevier B.V., 2004-10-01) Malavazi-Piza, K. C.; Araujo, M. S.; Godinho, R. O.; Tanaka, A. S.; Universidade Federal de São Paulo (UNIFESP)
    The carrageenan model of pleurisy is described as temporal plasma exudation (1-5 h) with extensive neutrophil infiltration and release of proteinases into the pleural cavity. the aim of this work was to study the effects of serine proteinase inhibitors on the inflammatory process induced by administration of caffageenan to the rat pleural cavity and on release of kinins in pleural exudate. Pleurisy was induced by injecting carrageenan and serine proteinase inhibitors simultaneously into the pleural cavity. the proteinase inhibitors used were: aprotinin, a plasma kallikrein inhibitor; recombinant leech derived tryptase inhibitor-2PL (LDTI-2PL), a plasmin inhibitor; Boophilus microplus trypsin inhibitors (BmTIs); trypsin; plasma kallikrein; plasmin and neutrophil elastase inhibitors; and a synthetic neutrophil elastase inhibitor (EIsynt). Administration of carrageenan with LDTI-2PL and BmTIs induced a marked increase in exudation (143% and 201%) and leukocyte migration (288% and 408%), respectively, when compared to the control group. Pleural exudate from LDTI-2PL and BmTIs plus carrageenan-treated rats showed a significant increase in plasma kallikrein-like activity, measured by chromogenic substrate hydrolysis. the specific inhibition of enzymatic activity with aprotinin confirmed that 50% of S2302 hydrolysis was produced by plasma kallikrein-like enzymes. Kinin release was increased by 97% and 103% in exudates from LDTI-2PL and BmTIs plus carrageenan-treated rats, respectively. Considering that the plasmin inhibitors LDTI-2PL and BmTIs increased exudation, leukocyte migration and bradykinin release, our results suggest an anti-inflammatory role for plasmin in the pleurisy model. (C) 2004 Elsevier B.V. All rights reserved.
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    Fibrinolytic activity is associated with presence of cystic medial degeneration in aneurysms of the ascending aorta
    (Wiley-Blackwell, 2010-12-01) Borges, Luciano F. [UNIFESP]; Gomez, Delphine; Quintana, Mercedes; Touat, Ziad; Jondeau, Guillaume; Leclercq, Anne; Meilhac, Olivier; Jandrot-Perrus, Martine; Gutierrez, Paulo S.; Freymuller, Edna [UNIFESP]; Vranckx, Roger; Michel, Jean-Baptiste; Univ Paris 07; Universidade Federal de São Paulo (UNIFESP); Ctr Reference Syndrome Marfan & Syndromes Apparen; Universidade de São Paulo (USP)
    Fibrinolytic activity is associated with presence of cystic medial degeneration in aneurysms of the ascending aortaAims:Thoracic ascending aortic aneurysms (TAA) are characterized by elastic fibre breakdown and cystic medial degeneration within the aortic media, associated with progressive smooth muscle cell (SMC) rarefaction. the transforming growth factor (TGF)-beta/Smad2 signalling pathway is involved in this process. Because the pericellular fibrinolytic system activation is able to degrade adhesive proteins, activate matrix metalloproteinase (MMP), induce SMC disappearance and increase the bioavailability of TGF-beta, the aim was to investigate the plasminergic system in TAA.Methods and results:Ascending aortas [21 controls and 19 TAAs (of three different aetiologies)] were analysed. Immunohistochemistry showed accumulation of t-PA, u-PA and plasmin in TAAs, associated with residual SMCs. Overexpression of t-PA and u-PA was confirmed by reverse transcription-polymerase chain reaction (RT-PCR), immunoblotting and zymography on TAA extracts and culture medium conditioned by TAA. Plasminogen was present on the SMC surface and inside cytoplasmic vesicles, but plasminogen mRNA was undetectable in the TAA medial layer. Plasmin-antiplasmin complexes were detected in TAA-conditioned medium and activation of the fibrinolytic system was associated with increased fibronectin turnover. Fibronectin-related material was detected immunohistochamically in dense clumps around SMCs and colocalized with latent TGF-beta binding protein-1.Conclusions:The fibrinolytic pathway could play a critical role in TAA progression, via direct or indirect impact on ECM and consecutive modulation of TGF-beta bioavailability.
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    Functional intersection of the kallikrein-related peptidases (KLKs) and thrombostasis axis
    (Walter de Gruyter & Co, 2010-04-01) Blaber, Michael; Yoon, Hyesook; Juliano, Maria A. [UNIFESP]; Scarisbrick, Isobel A.; Blaber, Sachiko I.; Florida State Univ; Universidade Federal de São Paulo (UNIFESP); Mayo Clin & Mayo Grad Sch Med; Mayo Grad Sch
    A large body of emerging evidence indicates a functional interaction between the kallikrein-related peptidases (KLKs) and proteases of the thrombostasis axis. These interactions appear relevant for both normal health as well as pathologies associated with inflammation, tissue injury, and remodeling. Regulatory interactions between the KLKs and thrombostasis proteases could impact several serious human diseases, including neurodegeneration and cancer. the emerging network of specific interactions between these two protease families appears to be complex, and much work remains to elucidate it. Complete understanding how this functional network resolves over time, given specific initial conditions, and how it might be controllably manipulated, will probably contribute to the emergence of novel diagnostics and therapeutic agents for major diseases.