Bài giảng Quá trình tiêu fibrin trình bày các nội dung chính sau: Các chất hoạt hóa plasminogen; Tác dụng của plasmin; Các chất ức chế hoạt hóa plasminogen; Các chất kháng plasmin không sinh lý.

Bài giảng Quá trình tiêu sợi huyết trình bày các nội dung chính sau: Plasminogen; Plasmin; Các chất hoạt hóa plasminogen; Hệ thống hoạt hóa phụ thuộc yếu tố XII; Các chất kháng plasmin không sinh lý.

The serpins are of general protein chemical interest due to their ability to undergo a large conformational change consisting of the insertion of the reactive centre loop (RCL) as strand 4 of the central b sheet A. To make space for the incoming RCL, the ‘shutter region’ opens by the b strands 3A and 5A sliding apart over the underlying a helix B. Loop insertion occurs during the formation of complexes of serpins with their target serine proteinases and during latency transition. This type of loop insertion is unique to plasminogen activator inhibitor-1 (PAI-1). We report here that amino-acid substitutions...

Bắt đầu từ những năm đầu thập niên 1970, các thành tựu về sinh học phân tử và kỹ thuật di truyền giúp chúng ta có thể hiểu rõ bản chất phân tử của các bệnh xuất hiện trên động vật, thực vật và đặc biệt là trên người. Giáo sư Paul Berg thuộc trường đại học Stanford (Hoa Kỳ), người được nhận giải Nobel hóa học năm 1980, là người đầu tiên tạo ra DNA tái tổ hợp (recombinant DNA- rDNA) vào năm 1972...

The serpin plasminogen activator inhibitor type 1 (PAI-1) plays an important role in physiological processes such as thrombolysis and ®brinolysis, as well as pathophysiological processes such as thrombosis, tumor invasion and metas-tasis. In addition to inhibiting serine proteases, mainly tissue-type (tPA) and urokinase-type (uPA) plasminogen activators, PAI-1 interacts with di€erent components of the extracellular matrix, i.e. ®brin, heparin (Hep) and vitronectin (Vn).

Matrilysin (matrix metalloproteinase-7) plays important roles in tumor progression. It was previously found that matrilysin binds to the surface of colon cancer cells to promote their metastatic potential. In this study, we identified annexin II as a novel membrane-bound substrate of matrilysin. Treatment of human colon cancer cell lines with active matrilysin released a 35 kDa annexin II form, which lacked its N-terminal region, into the culture supernatant. The release of the 35 kDa annexin II by matrilysin was significantly enhanced in the presence of serotonin or heparin....

Matrix metalloproteinase (MMP)-3 inhibited human MDA-MB-231 breast cancer cell invasion through recon-stituted basement membranein vitro. Inhibition of invasion was dependent upon plasminogen and MMP-3 activation, was impaired by the peptide MMP-3 inhibitor Ac-Arg-Cys-Gly-Val-Pro-Asp-NH2 and was associated with: rapid MMP-3-mediated plasminogen degradation to microplas-minogen and angiostatin-like fragments;

The importance of proteoglycans for secretionof proteolytic enzymes was studied in the murine macrophage cell line J774. Untreated or 4b-phorbol 12-myristate 13-acetate (PMA)-stimulated macrophages were treated with hexyl-b-D-thioxyloside to interfere with the attachment of glycosaminoglycan chains to their respective protein cores. Activation of the J774 macrophages with PMA resulted in increased secretion of trypsin-like serine proteinase activity.

Functional cooperationbetween integrins andgrowth factor receptors has been reported for several systems, oneofwhich is the modulation of insulin signaling by avb3 integrin. Plasminogen activator inhibitor type-1 (PAI-1), competes withavb3 integrin for vitronectin (VN) binding. Here we report that PAI-1, in a VN-dependent manner, prevents the cooperation of avb3 integrin with insulin signaling in NIH3T3 fibroblasts, resulting in a decrease in insulin-induced protein kinase B (PKB) phosphorylation, vascular endothelial growth factor (VEGF) expression and cell migration. ...

In the search for new ligands for the plasminogen kringle 4 binding-protein tetranectin, it has been found by ligand blot analysis andELISAthat tetranectinspecificallybound to the plasminogen-like hepatocyte growth factor and tissue-type plasminogen activator.The dissociation constants of these complexes were found to be within the same order of mag-nitude as the one for the plasminogen-tetranectin complex. The study also revealed that tetranectin did not interact with the kindred proteins: macrophage-stimulating protein, urokinase-type plasminogen activator and prothrombin....

Plasminogen activator inhibitor-1 (PAI-1) belongs to the serpin family of serine proteinase inhibitors. Serpins inhibit their target proteinases by an ester bond being formed between the active site serine of the proteinase and the P1 residue of the reactive centre loop (RCL) of the serpin, fol-lowed by insertion of the RCL intob-sheet A of the serpin. Concomitantly, there are conformational changes in the flexible joint region lateral tob-sheet A.

The serpin plasminogen activator inhibitor-1 (PAI-1) is a fast and specific inhibitor of the plasminogen activating serine proteases tissue-type and urokinase-type plasminogen activator and, as such, an important regulator in turnover of extracellularmatrixand infibrinolysis. PAI-1 spontaneously loses its antiproteolyticactivityby inserting its reactive centre loop (RCL) as strand 4 in b-sheet A, thereby converting to the so-called latent state.

Thrombomodulin (TM) slows down the interaction rate between thrombin and plasminogen activator inhibitor 1 (PAI-1). We now show that the 12-fold reduced inhibition rate in the presence ofTM does not result from an altered distribution between PAI-1 cleavage and irreversible com-plex formation. Surface plasmon resonance (SPR) revealed an over 200-fold reduced affinity of TM for thrombin-VR1 tPA as compared to thrombin, demonstrating the importance ofthe VR1 loop in the interaction ofthrombin withbothTMandPAI-1....

Plasminogen activator inhibitor type-2 (PAI-2) is a nonconventional serine protease inhibitor (serpin) with unique and tantalizing properties that is generally considered to be an authentic and physiological inhibitor of uro-kinase. However, the fact that only a small percentage of PAI-2 is secreted has been a long-standing argument for alternative roles for this serpin. Indeed, PAI-2 has been shown to have a number of intracellular roles: it can alter gene expression, influence the rate of cell proliferation and differ-entiation, and inhibit apoptosis in a manner independent of urokinase inhi-bition. ...

Plasmin(ogen) kringles 1 and 4 are involved in anchorage of plasmin(ogen) to fibrin and cells, an essential step in fibrinolysis and pericellular proteo-lysis. Their contribution to these processes was investigated by selective neutralization of their lysine-binding function. Blocking the kringle 1 lysine-binding site with monoclonal antibody 34D3 fully abolished binding and activation of Glu-plasminogen and prevented both fibrinolysis and plasmin-induced cell detachment-induced apoptosis.

We recently discovered several nonlysine-analog conforma-tional modulators for plasminogen. These include SMTP-6, thioplabin B and complestatin that are low molecular mass compounds of microbial origin. Unlike lysine-analog mod-ulators,which increaseplasminogenactivationbut inhibit its binding to fibrin, the nonlysine-analog modulators enhance both activation and fibrin binding of plasminogen. Here we show that some nonlysine-analog modulators promote autoproteolyticgenerationof plasmin(ogen) derivativeswith its catalytic domain undergoing extensive fragmentation (PMDs), which have angiostatin-like anti-endothelial activ-ity....

Some endocytosis receptors related to the low-density lipoprotein receptor, including low-density lipoprotein receptor-related protein-1A, very-low-density lipoprotein receptor, and sorting protein-related receptor, bind pro-tease-inhibitor complexes, including urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), and the uPA–PAI-1 com-plex.

Tissue-type plasminogen activator (t-PA) has recently been identified as a modulator of neuronal plasticity and can initiate conversion of the pro-form of brain-derived neurotrophic factor (BDNF) into its mature form. BDNF also increases t-PA gene expression implicating t-PA as a downstream effector of BDNF function.

Plasminogen activator inhibitor type 2 (PAI-2; SERPINB2)is a highly-regulated gene that is subject to both transcriptional and post-transcrip-tional control. For the latter case, inherent PAI-2 mRNA instability was previously shown to require a nonameric adenylate-uridylate element in the 3¢ UTR.

Bệnh tim mạch là các bệnh liên quan đến những rối loạn ảnh hưởng tới tim và các mạch máu bao gồm bệnh mạch vành, bệnh mạch máu não, bệnh mạch máu ngoại biên và tăng huyết áp. Bệnh tim mạch là nguyên nhân hàng đầu gây tử vong trên thế giới. Mỗi năm, bệnh tim mạch là nguyên nhân gây tử vong cho 17,5 triệu người và dự đoán sẽ có khoảng 25 triệu người bị bệnh tim mạch tử vong vào năm 2020. Bệnh tim mạch cũng được dự đoán sẽ là nguyên nhân lớn nhất gây tàn phế cho người vào năm 2020....