Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thrombin has multiple functions, including its function as a key enzyme during blood coagulation and other physiologic activities. We studied brain tissue reactions to thrombin that might be present in the central nervous system (CNS) following injury. Thrombin and three different types of controls--buffer, albumin, and plasmin--were individually infused into the rat caudate nucleus by a continuous osmotic mini-pump. Brains were examined by conventional histologic and immunohistologic techniques. Antibodies for bromodeoxyuridine (BrdU), glial fibrillary acidic protein (GFAP), vimentin, and laminin were employed to assess the infiltration of inflammatory cells, proliferation activity of cells, and reaction of astrocytes and mesenchymal cells, respectively. The number of inflammatory cells, number of BrdU-positive cells, area and number of vimentin-positive astrocytes, and the area of GFAP-positive astrocytes were quantitatively analyzed. Thrombin caused infiltration of inflammatory cells, proliferation of mesenchymal cells, induction of angiogenesis, and an increase in vimentin-positive reactive astrocytes. These histologic changes caused by thrombin infusion resembled the inflammation, scar formation, and reactive gliosis in the CNS following injury. These results suggest that thrombin may play an important role in inflammatory responses to CNS injury since thrombin is one of the blood borne factors that may interact with brain tissue after CNS injury. The data further suggest that the therapeutic application of antithrombin agents for CNS injury suppresses inflammation and the excessive gliosis and scar formation, which are barriers to neuronal regeneration.
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PMID:Thrombin may contribute to the pathophysiology of central nervous system injury. 769 71

To identify the element(s) in nucleolar proteins which determine nucleolus-specific topogenesis, we have used different kinds of cDNA constructs encoding various chimeric combinations of mutants of the constitutive nucleolar protein NO38 (B23): 1) with an amino terminally placed short "myc tag"; 2) with two different carboxyl terminally attached large alpha-helical coiled coil structures, the lamin A rod domain or the rod domain of vimentin; 3) with the sequence-related nucleoplasmic histone-binding protein nucleo-plasmin; and 4) with the soluble cytoplasmic protein pyruvate kinase. To avoid the problem of formation of complexes with endogenous wild-type (wt) molecules and "piggyback" localization, special care was taken to secure that the mutants and chimeras used did not oligomerize as is typical of protein NO38 (B23). Using microinjection and transfection of cultured cells, we found that the segment comprising the amino-terminal 123 amino acids (aa) alone was sufficient to effect nucleolar accumulation of the construct molecules, including the chimeras with the entire rod domains of lamin A and vimentin. However, when the amino-terminal 109 aa were deleted, the molecules still associated with the nucleolus. The results of further deletion experiments and of domain swaps with nucleoplasmin all point to the topogenic importance of two independent molecular regions located at both the amino- and carboxyl-terminal end. Our definition of dominant elements determining the nucleolar localization of protein NO38 (B23) as well as of diverse nonnucleolar proteins will help to identify its local binding partner(s) and functions, the construction of probes examining other proteins or sequence elements within the nucleolar microenvironment, and the generation of cells with an altered nuclear architecture.
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PMID:Topogenesis of a nucleolar protein: determination of molecular segments directing nucleolar association. 919 Feb 4