The Experts below are selected from a list of 52098 Experts worldwide ranked by ideXlab platform
Motoharu Seiki - One of the best experts on this subject based on the ideXlab platform.
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processing of a precursor of 72 kilodalton type iv collagenase gelatinase a by a recombinant membrane type 1 matrix metalloproteinase
Cancer Research, 1996Co-Authors: Takeshi Kinoshita, Takahisa Takino, Michiyasu Itoh, Toshifumi Akizawa, Hiroshi Sato, Motoharu SeikiAbstract:Membrane-type 1 matrix metalloproteinase that is associated with the proteolytic activation of progelatinase A was expressed as a recombinant fusion protein in Escherichia coli . The recombinant enzyme cleaved the propeptide sequence of gelatinase A in a sequence-specific manner. A mutant progelatinase A that has a substitution of Asn66-Leu to Ile-Val was not processed at all. The processing was blocked by tissue inhibitor of Metalloproteinases-2 or BB-94 but not by tissue inhibitor of Metalloproteinases-1. Thus, membrane-type 1 matrix metalloproteinase is a direct activator of progelatinase A without requiring additional proteases.
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tissue inhibitor of metalloproteinase 1 is a negative regulator of the metastatic ability of a human gastric cancer cell line kkls in the chick embryo
Cancer Research, 1993Co-Authors: Yuri Tsuchiya, Hiroshi Sato, Yasunori Okada, Yoshio Endo, Masayosi Mai, Takuma Sasaki, Motoharu SeikiAbstract:Abstract Tissue inhibitors of Metalloproteinases (TIMPs) are the negative regulators of matrix Metalloproteinases that degrade extracellular matrix. We examined the regulatory role of TIMP-1 in the metastatic activity of human gastric cancer cell lines in chick embryos because unregulated matrix metalloproteinase activities are believed to be essential during metastatic processes. One of the nine cell lines examined, KKLS cells, formed metastatic colonies in the chick livers. These cells expressed undetectable levels of TIMP-1, and this was not inducible by 12- O -tetradecanoylphorbol 13-acetate. Derivatives of KKLS cells with different levels of TIMP-1 expression were prepared by transfection of the human TIMP-1 complementary DNA controlled by a simian virus 40 early promoter. Metastatic abilities were suppressed by almost 70% in the transfectants expressing high levels of TIMP-1. In contrast, no suppression was observed in the control transfectants or in cells expressing the transfected TIMP-1 gene at low levels. These data indicate that a reduced expression of TIMP-1 in KKLS cells is responsible for their consequent metastatic potential. Moreover, it suggests that matrix metalloproteinase enzymatic activities are a prerequisite for metastatic activity in this experimental model system.
Hiroshi Sato - One of the best experts on this subject based on the ideXlab platform.
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processing of a precursor of 72 kilodalton type iv collagenase gelatinase a by a recombinant membrane type 1 matrix metalloproteinase
Cancer Research, 1996Co-Authors: Takeshi Kinoshita, Takahisa Takino, Michiyasu Itoh, Toshifumi Akizawa, Hiroshi Sato, Motoharu SeikiAbstract:Membrane-type 1 matrix metalloproteinase that is associated with the proteolytic activation of progelatinase A was expressed as a recombinant fusion protein in Escherichia coli . The recombinant enzyme cleaved the propeptide sequence of gelatinase A in a sequence-specific manner. A mutant progelatinase A that has a substitution of Asn66-Leu to Ile-Val was not processed at all. The processing was blocked by tissue inhibitor of Metalloproteinases-2 or BB-94 but not by tissue inhibitor of Metalloproteinases-1. Thus, membrane-type 1 matrix metalloproteinase is a direct activator of progelatinase A without requiring additional proteases.
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tissue inhibitor of metalloproteinase 1 is a negative regulator of the metastatic ability of a human gastric cancer cell line kkls in the chick embryo
Cancer Research, 1993Co-Authors: Yuri Tsuchiya, Hiroshi Sato, Yasunori Okada, Yoshio Endo, Masayosi Mai, Takuma Sasaki, Motoharu SeikiAbstract:Abstract Tissue inhibitors of Metalloproteinases (TIMPs) are the negative regulators of matrix Metalloproteinases that degrade extracellular matrix. We examined the regulatory role of TIMP-1 in the metastatic activity of human gastric cancer cell lines in chick embryos because unregulated matrix metalloproteinase activities are believed to be essential during metastatic processes. One of the nine cell lines examined, KKLS cells, formed metastatic colonies in the chick livers. These cells expressed undetectable levels of TIMP-1, and this was not inducible by 12- O -tetradecanoylphorbol 13-acetate. Derivatives of KKLS cells with different levels of TIMP-1 expression were prepared by transfection of the human TIMP-1 complementary DNA controlled by a simian virus 40 early promoter. Metastatic abilities were suppressed by almost 70% in the transfectants expressing high levels of TIMP-1. In contrast, no suppression was observed in the control transfectants or in cells expressing the transfected TIMP-1 gene at low levels. These data indicate that a reduced expression of TIMP-1 in KKLS cells is responsible for their consequent metastatic potential. Moreover, it suggests that matrix metalloproteinase enzymatic activities are a prerequisite for metastatic activity in this experimental model system.
G Murphy - One of the best experts on this subject based on the ideXlab platform.
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Induction of matrix metalloproteinase activation cascades based on membrane-type 1 matrix metalloproteinase: associated activation of gelatinase A, gelatinase B and collagenase 3.
The Biochemical journal, 1998Co-Authors: Stuart Cowell, J J Reynolds, Marie-pia D'ortho, Carlos López-otín, R M Hembry, Heather Stanton, Vera Knäuper, M.l Stewart, G MurphyAbstract:SW1353 chondrosarcoma cells cultured in the presence of interleukin-1, concanavalin A or PMA secreted procollagenase 3 (matrix metalloproteinase-13). The enzyme was detected in the culture medium by Western blotting using a specific polyclonal antibody raised against recombinant human procollagenase 3. Oncostatin M enhanced the interleukin-1-induced production of procollagenase 3, whereas interleukin-4 decreased procollagenase 3 synthesis. The enzyme was latent except when the cells had been treated with concanavalin A, when a processed form of 48 kDa, which corresponds to the active form, was found in the culture medium and collagenolytic activity was detected by degradation of 14C-labelled type I collagen. The concanavalin A-induced activation of procollagenase 3 coincided with the processing of progelatinase A (matrix metalloproteinase-2) by the cells, as measured by gelatin zymography. In addition, progelatinase B (matrix metalloproteinase-9) was activated when gelatinase A and collagenase 3 were in their active forms. Concanavalin A treatment of SW1353 cells increased the amount of membrane-type-1 matrix metalloproteinase protein in the cell membranes, suggesting that this membrane-bound enzyme participates in an activation cascade involving collagenase 3 and the gelatinases. This cascade was effectively inhibited by tissue inhibitors of Metalloproteinases-2 and -3. Tissue inhibitor of Metalloproteinases-1, which is a much weaker inhibitor of membrane-type 1 matrix metalloproteinase than tissue inhibitors of Metalloproteinases-2 and -3 [Will, Atkinson, Butler, Smith and Murphy (1996) J. Biol. Chem. 271, 17119-17123], was a weaker inhibitor of the activation cascade.
Takeshi Kinoshita - One of the best experts on this subject based on the ideXlab platform.
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processing of a precursor of 72 kilodalton type iv collagenase gelatinase a by a recombinant membrane type 1 matrix metalloproteinase
Cancer Research, 1996Co-Authors: Takeshi Kinoshita, Takahisa Takino, Michiyasu Itoh, Toshifumi Akizawa, Hiroshi Sato, Motoharu SeikiAbstract:Membrane-type 1 matrix metalloproteinase that is associated with the proteolytic activation of progelatinase A was expressed as a recombinant fusion protein in Escherichia coli . The recombinant enzyme cleaved the propeptide sequence of gelatinase A in a sequence-specific manner. A mutant progelatinase A that has a substitution of Asn66-Leu to Ile-Val was not processed at all. The processing was blocked by tissue inhibitor of Metalloproteinases-2 or BB-94 but not by tissue inhibitor of Metalloproteinases-1. Thus, membrane-type 1 matrix metalloproteinase is a direct activator of progelatinase A without requiring additional proteases.
Gary A Rosenberg - One of the best experts on this subject based on the ideXlab platform.
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matrix Metalloproteinases and their multiple roles in neurodegenerative diseases
Lancet Neurology, 2009Co-Authors: Gary A RosenbergAbstract:Summary Matrix Metalloproteinases (MMPs) and proteins containing a disintegrin and metalloproteinase domain (ADAM) are important in neuroinflammation, and recent studies have linked their actions to neurodegenerative disorders. MMPs act as cell-surface sheddases and can affect cell signalling initiated by growth factors or death receptors. Four tissue inhibitors of Metalloproteinases (TIMPs) regulate metalloproteinase activity. These proteases increase the permeability of the blood–brain barrier, which can cause oedema, haemorrhage, and cell death. MMPs also participate in tissue repair by promoting angiogenesis and neurogenesis. In vascular cognitive impairment, MMPs change permeability of the blood–brain barrier and might contribute to white matter damage. MMPs and ADAMs might contribute to the formation and degradation of amyloid proteins in Alzheimer's disease and cause death of dopaminergic neurons in Parkinson's disease. In this Review, by examining the effects of neuroinflammation, we try to understand the role that MMPs might have in neurodegenerative diseases. Therapeutic strategies that use inhibitors of MMPs could represent potential novel treatments for neurological diseases.
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tissue inhibitor of Metalloproteinases 3 and matrix metalloproteinase 3 regulate neuronal sensitivity to doxorubicin induced apoptosis
European Journal of Neuroscience, 2003Co-Authors: M Wetzel, Gary A Rosenberg, Lee Anna CunninghamAbstract:Metalloproteinase activity at the cell surface influences cellular sensitivity to extrinsic death vs. survival signals in a variety of cell types, through proteolytic shedding of cell surface signalling molecules. Tissue inhibitor of Metalloproteinases-3 (TIMP-3) is a unique natural metalloproteinase inhibitor that plays a pro-apoptotic role through its ability to inhibit Metalloproteinases that proteolytically cleave death receptors and their ligands from the cell surface. To study the convergence of metalloproteinase activity and death receptor signalling in neurons, we established an in vitro model of neuronal apoptosis utilizing the chemotherapeutic drug, doxorubicin (Dox). Primary cultures established from embryonic rat cerebral cortices displayed robust and selective neuronal apoptosis in response to Dox, an effect that was dependent on the activation of the death receptor, Fas. We demonstrate that both TIMP-3 and matrix metalloproteinase-3 (MMP-3) are constitutively expressed by primary cortical neurons in culture, and selectively modulated Fas-mediated neuronal apoptosis induced by Dox. Metalloproteinase inhibition by TIMP-3 was found to be necessary for Dox-induced neuronal death, whereas addition of active MMP-3 markedly attenuated apoptosis and diminished Fas-Fas ligand interaction at the cell surface. These observations implicate a physiological role for the balance of TIMP-3 and MMP-3 activity at the neuronal surface in regulating death receptor sensitivity. The convergence of metalloproteinase activity and death receptor signalling at the cell surface may influence neuronal cell death vs. survival decisions.
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matrix Metalloproteinases in cerebrovascular disease
Journal of Cerebral Blood Flow and Metabolism, 1998Co-Authors: Sheila Munbryce, Gary A RosenbergAbstract:Cerebral ischemia and intracerebral hemorrhage cause extensive damage to neurons, disrupt the extracellular matrix, and increase capillary permeability. Multiple substrates participate in the cellular damage, including free radicals and proteases. Matrix Metalloproteinases and serine proteases are two classes of proteases that are normally present in brain in latent forms, but once activated, contribute to the injury process. These enzymes have a unique role in the remodeling of the extracellular matrix and in the modulation of the capillary permeability. Intracerebral injection of the matrix metalloproteinase, type IV collagenase, attacks the basal lamina around the capillary and opens the blood-brain barrier. Extracellular matrix-degrading proteases are induced by immediate early genes and cytokines, and regulated by growth factors. Activity of the matrix Metalloproteinases is tightly controlled by activation mechanisms and tissue inhibitors of Metalloproteinases. During ischemia and hemorrhage, multiple matrix Metalloproteinases and serine proteases are produced along with their inhibitors. These proteolytic enzymes are involved in the delayed injury that accompanies the neuroinflammatory response. Synthetic inhibitors to Metalloproteinases reduce proteolytic tissue damage, and may limit secondary neuroinflammation.