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T Takino

Publications and source records attributed to T Takino.

At least 37 records · Page 2Linked to original sources
PubMed1996

Expression of membrane-type matrix metalloproteinase 1 (MT1-MMP) in tumor cells enhances pulmonary metastasis in an experimental metastasis assay.

Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a member of the recently identified unique membrane-type subgroup in the matrix metalloproteinase (MMP) family. MT1-MMP has proteolytic activity against components in the extracellular matrix and activates progelatinase A (72-kDa type IV procollagenase/proMMP-2) on the cell surface. Because MT1-MMP is frequently expressed in a variety of tumors, we examined its contribution to their metastatic potential. The mouse lung carcinoma cell line Madison 109 was transiently transfected with a MT1-MMP expression plasmid and inoculated into the tail vein of BALB/c mouse. Fate of the transfected cells was monitored by the neo(r) gene in the plasmid using the quantitative PCR method. The survival rate of the parental cells in lung was 0.7% of the inoculated cells. It was increased by 3-fold with the MT1-MMP transfected cells and the number of the lung nodules increased accordingly. Immunostaining of the consecutive tissue sections revealed that lung nodules expressing MT1-MMP were positive for gelatinase A as well, whereas MT1-MMP-negative cells were not stained for gelatinase A at all. Thus, MT1-MMP-expressing cells acquire specific ability to bind exogenous progelatinase A.

Animals↗
PubMed1996

Activation of a recombinant membrane type 1-matrix metalloproteinase (MT1-MMP) by furin and its interaction with tissue inhibitor of metalloproteinases (TIMP)-2.

Membrane type 1-matrix metalloproteinase (MT1-MMP) initiates the activation of the zymogen progelatinase A/ 72-kDa type IV collagenase by cleavage of the Asn66-Leu peptide bond. We previously pointed out that MT1-MMP possesses a unique amino acid sequence Arg-Arg-Lys-Arg111 which is a potential recognition sequence for furin-like proteases (Nature, 370 (1994) 61-65). Here, using a recombinant MT1-MMP expressed in Escherichia coli we demonstrated that furin specifically cleaves MT1-MMP between Arg111-Tyr in vitro, which resulted in a stimulation of progelatinase A-activation function. Tissue inhibitor of metalloproteinases (TIMP)-2 inhibited activation of progelatinase A by forming a stable complex with activated MT1-MMP.

Arginine↗
PubMed1996

Processing of a precursor of 72-kilodalton type IV collagenase/gelatinase A by a recombinant membrane-type 1 matrix metalloproteinase.

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 Asn(66)-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.

Animals↗
PubMed1996

Cell surface binding and activation of gelatinase A induced by expression of membrane-type-1-matrix metalloproteinase (MT1-MMP).

Gelatinase A is secreted as a proenzyme (progelatinase A) which is activated and bound on the surface of tumor and normal cells. We have reported that the expression of a membrane-type-1-matrix metalloproteinase (MT1-MMP) induces activation of progelatinase A. Here we demonstrate that the expression of MT1-MMP in COS-1 cells induces cell-surface binding of progelatinase A which is consequently processed to an intermediate form. Processing from the intermediate to the fully active form is dependent on the gelatinase A concentration. These results suggest that the cell-surface binding concentrates the gelatinase A intermediate form locally to allow autoproteolytic processing to the fully active form.

Animals↗
PubMed1996

MT-MMP, the cell surface activator of proMMP-2 (pro-gelatinase A), is expressed with its substrate in mouse tissue during embryogenesis.

Matrix metalloproteinases (MMPs), which degrade the components of the extracellular matrix, are key enzymes involved in the tissue remodeling of multicellular organisms. Since MMPs are secreted as inactive zymogens (pro-MMPs), they have to be activated to function. We identified a membrane-type MMP (MT-MMP) that activated proMMP-2 (pro-gelatinase A = 72 kDa type IV pro-collagenase) and described its expression on the invasive tumor cell surface. In this study we further examined the expression and role of MT-MMP in the activation of proMMP-2 during mouse embryogenesis. Northern blotting demonstrated that MT-MMP expression was increased together with that of MMP-2 and its inhibitor gene, TIMP-2, in embryos depending upon the number of days after gestation, and decreased with maturation after birth. In situ hybridization and immunohistochemistry localized MT-MMP mRNA and protein in the cells of ossifying tissues where both MMP-2 and TIMP-2 were expressed. Activated MMP-2 was detected by gelatin zymography in the lysates prepared from the micro dissected tissues that expressed the three genes. The activation rate of proMMP-2 was proportional to the expression of MMP-2 and MT-MMP. These results indicated that proMMP-2 activation through its activator, MT-MMP, is a physiological system used by organisms to initiate tissue remodeling on the cell surface.

Amino Acid Sequence↗
PubMed1995

Changes in epidural pressure during walking in patients with lumbar spinal stenosis.

STUDY DESIGN: This study was done to assess the pathophysiology of neurogenic intermittent claudication by measuring the epidural pressure at walking. OBJECTIVES: Changes in epidural pressure during walking in patients with neurogenic intermittent claudication and in normal individuals were analyzed. SUMMARY OF BACKGROUND DATA: Neurogenic intermittent claudication may be caused by compression of the nerve roots or may be a result of nerve root ischemia. The exact pathogenesis of neurogenic intermittent claudication is uncertain. METHODS: Local epidural pressure changes at the stenotic level during walking were analyzed in 12 patients with lumber spinal stenosis and seven normal individuals. a flexible pressure transducer was inserted into the epidural space and placed at the L4-L5 level. The epidural pressure was monitored continuously during walking. The pattern of the pressure change was assessed by gait analysis using a foot switch. RESULTS: The pressure was changed during walking. The pressure had a wave pattern of increase and decrease, and this pattern was repeated during walking. Intermittent pressure increase was seen about 90 times per minute while walking at a velocity of 2 km/h. An increase in epidural pressure occurred at the double-supporting phase in each gait cycle. CONCLUSIONS: The pressure was high in spinal stenosis and low in normal individuals. The increase of epidural pressure at simple walking was higher than walking with lumbar flexion. Intermittent compression to the nerve roots during walking may be a cause of neurogenic intermittent claudication.

Aged↗
PubMed1995

Identification of the second membrane-type matrix metalloproteinase (MT-MMP-2) gene from a human placenta cDNA library. MT-MMPs form a unique membrane-type subclass in the MMP family.

Membrane-type matrix metalloproteinase (MT-MMP), which we have identified recently, is unique in its transmembrane (TM) domain at the C terminus and mediates activation of pro-gelatinase A on the cell surface (Sato, H., Takino, T., Okada, Y., Cao, J., Shinagawa, A., Yamamoto, E., and Seiki, M. (1994) Nature 370, 61-65; Takino, T., Sato, H., Yamamoto, E., and Seiki, M. (1995) Gene (Amst.) 115, 293-298). In addition to MT-MMP, a novel MMP-related cDNA of 2.1 kilobases was isolated from a human placenta cDNA library. The cDNA contains an open reading frame for a new MMP. The deduced protein composed of 604 amino acids was closely related to MT-MMP in the amino acid sequence (66% homology at the catalytic domains) and has a potential TM domain at the C terminus. Monoclonal antibodies raised against the synthetic peptide recognized a 64-kDa protein as the major product in the transfected cells. TIMP-1 fused with the potential TM domain was localized on the cell surface while native TIMP-1 is in the culture medium. Thus, we called the second membrane-type MMP, MT-MMP-2 and renamed MT-MMP, MT-MMP-1. MT-MMP-1 and -2 are thought to form a distinct membrane-type subclass in the MMP family since all the others are secreted as soluble forms. Like MT-MMP-1, expression of MT-MMP-2 induced processing of pro-gelatinase A (68-kDa in gelatin zymography) into the activated form of 62-kDa fragments through a 64-kDa intermediate form. Expression of MT-MMP-2 mRNA was at the highest levels in the brain where MT-MMP-1 was at the lowest level compared to other tissues. MT-MMP-1 and -2 are thought to be utilized for extracellular matrix turnover on the surface of cells under different genetic controls.

Amino Acid Sequence↗
PubMed1995

Cloning of a human gene potentially encoding a novel matrix metalloproteinase having a C-terminal transmembrane domain.

Matrix metalloproteinases (MMPs) play key roles in tissue remodeling during physiological and pathological processes by degrading various extracellular matrix (ECM) components. Although nine distinct MMPs have been characterized by cDNA cloning, there are thought to be more corresponding to the complexity of the ECM. MMP genes expressed in human tissues and cell lines were analyzed by the polymerase chain reaction (PCR) using degenerate primers that corresponded to the conserved amino acid (aa) sequences of the MMPs. One isolated complementary DNA (cDNA) fragment had sequence homology to the reported MMPs, but was otherwise unique. A human placenta cDNA library (Clontech) was screened using the fragment as a probe and a 3.4-kb cDNA fragment containing a long open reading frame (potentially encoding 582 aa) was isolated. The putative gene product had a common domain structure and the conserved sequence of a MMP, but it had a unique transmembrane (TM)-like structure at the C terminus. It should, therefore, be an TM protein, whereas all the other reported MMPs are secretory proteins. Thus, the gene is thought to be the first of a new subclass of MMPs whose products are potentially expressed on the cell surface.

Adenocarcinoma↗
PubMed1995

Epidural pressure measurements. Relationship between epidural pressure and posture in patients with lumbar spinal stenosis.

STUDY DESIGN: The relationship between epidural pressure and lumbar posture was assessed in patients with lumbar spinal stenosis. OBJECTIVES: This study was performed to assess the relationship between epidural pressure and lumbar posture in patients with lumbar spinal stenosis. METHODS: The study was performed on 10 patients who had cauda equina symptoms at the L4-L5 level. The catheter transducer was inserted into the epidural space through L5-S1 interlaminar space and placed at the L4-L5 disc level. This transducer was connected with an amplifier and a recorder. Epidural pressure was continuously measured in various postures. RESULTS: Local epidural pressure at the stenotic level was low in lying and sitting postures, and high in standing postures. Pressure was increased with extension, but decreased with flexion. The highest pressure was 116.7 +/- 38.4 mm Hg in standing with extension. CONCLUSION: Epidural pressure was significantly related to posture. These pressure changes correlated with the development of cauda equina symptoms. The increase of epidural pressure by posture may induce compression of the cauda equina. These pressure changes may explain the postural dependency in eliciting symptoms.

Aged↗
PubMed1995

The C-terminal region of membrane type matrix metalloproteinase is a functional transmembrane domain required for pro-gelatinase A activation.

We identified a new matrix metalloproteinase (membrane type matrix metalloproteinase (MT-MMP)) that has a potential transmembrane (TM) domain at the C terminus and reported its expression on the surface of invasive tumor cells. The expression of MT-MMP induced specific activation of 72-kDa pro-gelatinase A (Sato, H., Takino, T., Okada, Y., Cao, J., Shinagawa, A., Yamamoto, E., and Seiki, M. (1994) Nature 370, 61-65). Thus, MT-MMP on the cell surface is thought to play an important role in various physiological and pathological processes accompanying tissue remodeling. In this study, we demonstrated that the potential TM domain deduced from the amino acid sequence functions as a membrane linker when it is fused to a secretory protein, tissue inhibitor of matrix metalloproteinases-1. The pro-gelatinase A activation function of MT-MMP was abolished by truncation of the TM domain and recovered by fusing the MT-MMP mutant with the TM domain of interleukin 2 receptor alpha-chain. The truncated MT-MMP was released from the cells into the medium and detected as processed or modified forms. In spite of the deletion of the TM domain some portions of the mutant MT-MMP were still retained on the surface of cells. Thus, MT-MMP has an additional device to keep it on the cell surface. The TM domain however, plays an essential role in the pro-gelatinase A activation function of MT-MMP, probably regulating its fine orientation or the localization that is necessary to interact with substrate.

Animals↗
PubMed1995

Schmorl's nodes and low-back pain. Analysis of magnetic resonance imaging findings in symptomatic and asymptomatic individuals.

Magnetic resonance imaging (MRI) findings in cases with symptomatic and asymptomatic Schmorl's nodes have been analysed. In all symptomatic cases, the vertebral body marrow surrounding the Schmorl's node was seen as low signal intensity on T1-weighted images and as high signal intensity on T2-weighted images. It was confirmed by histological examination that the MRI findings indicated the presence of inflammation and oedema in the vertebral bone marrow. These MRI findings were not seen in asymptomatic individuals. Inflammatory changes in the vertebral body marrow induced by intraosseous fracture and biological reactions to intraspongious disc materials might cause pain. We postulate that after fracture healing and subsidence of inflammation, the Schmorl's nodes become asymptomatic, in analogy with old vertebral compression fractures. MRI is not only useful in detecting the recently developed Schmorl's nodes but also in differentiating between symptomatic and asymptomatic Schmorl's nodes.

Adolescent↗
PubMed1995

Transient cortical blindness following bypass graft angiography. A case report.

Transient cortical blindness, an uncommonly recognized complication of cerebral angiography, is an exceedingly rare event after cardiac catheterization and angiography. This report describes a sixty-two-year-old patient who had transient cortical blindness following bypass graft angiography. In this case, the authors showed that cortical blindness was associated with the breakage of the blood-brain barrier (BBB) and an increase in vascular permeability rather than with primary cerebral circulatory insufficiency. When the possibility exists that an excess volume of contrast medium may enter the cerebral circulation as in this case, that is, following a coronary artery bypass graft (CABG) using the internal mammary artery (IMA), precautionary measures may be necessary such as changing the type of contrast medium to be used or decreasing the volume injected. When cortical blindness occurs, it is a serious clinical problem whether transient or permanent. Therefore, the circumstances leading to this complication should be understood to determine suitable treatment and management.

Blindness↗
PubMed1995

[Molecular biology of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), and the regulation of these genes in tumor tissues].

Degradation of the extracellular matrix (ECM) is required for tumor invasion and metastasis. Matrix metalloproteinases (MMPs), which degrade the various ECM components, are thought to play key roles in these processes. The activity of MMPs is strictly controlled at the following three steps, gene expression, proenzyme activation and inhibition by tissue inhibitors of metalloproteinases (TIMPs). Overexpression of MMP genes and ECM degrading activities have reported to be associated with the invasive and metastatic tumor cells. Many researchers have been reported that these phenotypes of tumor cells were inhibited by TIMPs. Thus, the potential of tumor cells to invade into the ECM is regulated by the balance of MMPs and TIMPs.

Collagenases↗
PubMed1994

A matrix metalloproteinase expressed on the surface of invasive tumour cells.

Gelatinase A (type-IV collagenase; M(r) 72,000) is produced by tumour stroma cells and is believed to be crucial for their invasion and metastasis, acting by degrading extracellular matrix macro-molecules such as type IV collagen. An inactive precursor of gelatinase A (pro-gelatinase A) is secreted and activated in invasive tumour tissue as a result of proteolysis which is mediated by a fraction of tumour cell membrane that is sensitive to metalloproteinase inhibitors. Here we report the cloning of the complementary DNA encoding a new matrix metalloproteinase with a potential transmembrane domain. Expression of the gene product on the cell surface induces specific activation of pro-gelatinase A in vitro and enhances cellular invasion of the reconstituted basement membrane. Tumour cells of invasive lung carcinomas, which contain activated forms of gelatinase A, were found to express the transcript and the gene product. The new metalloproteinase may thus trigger invasion by tumour cells by activating pro-gelatinase A on the tumour cell surface.

3T3 Cells↗
PubMed1994

Inhibition of Ca(2+)-induced aggregation of porcine intestinal brush-border membranes by lipid peroxidation.

The effects of lipid peroxidation on Ca(2+)-induced aggregation of porcine intestinal brush-border membranes were examined using a system consisting of ascorbic acid/Fe2+/tert-butyl hydroperoxide (t-BuOOH). Incubation of the membranes with ascorbic acid/Fe2+/t-BuOOH resulted in inhibition of Ca(2+)-induced aggregation of the membranes with the formation of thiobarbituric acid-reactive substances, depending on the hydroperoxide concentration and the incubation time. The inhibition of the membrane aggregation associated with ascorbic acid/Fe2+/t-BuOOH treatment was effectively prevented by the addition of an antioxidant, 3(2)-tert-butyl-4-hydroxyanisole, to the reaction mixture. Studies with 8-anilino-1-naphthalenesulfonate (ANS) revealed that there is a linear relationship between the apparent dissociation constants (Kd) of ANS-membrane complexes and the aggregating efficiencies of the membranes with different levels of lipid peroxidation This suggests that inhibition of the membrane aggregation by lipid peroxidation involves a change in the membrane surface charge density. Modification of the membranes with malondialdehyde also resulted in a decrease in the aggregating efficiency of the membranes with a decrease in the Kd value of ANS-membrane complex. In addition, the contribution of the lipid organization to membrane aggregation was examined by measuring the fluorescence anisotropy of diphenylhexatriene-labeled membranes in the presence of a lipid fluidizer, benzyl alcohol. The results are discussed in terms of peroxidation-induced inhibition of intramembrane interactions of the membranes.

Animals↗
PubMed1994

Long circulating emulsion carrier systems for highly lipophilic drugs.

With the aim of developing of emulsion carrier systems for lipophilic drugs with the potential for prolonged circulation in the blood or hepatic targeting, the in vivo disposition of four model compounds, i.e., [3H]prostaglandin E1, [3H]retinoic acid, [14C]cholesterol, and [14C]cholesteryl oleate with calculated log PC(oct) values of 2.15, 6.61, 9.46, and 18.3, respectively, injected with various emulsion formulations, were studied in mice. Small sized emulsions of about 100 nm in diameters, with compositions of egg phosphatidylcholine (PC): soybean oil = 1:1 (small PC emulsion) and PC: egg sphingomyelin (SM): soybean oil = 0.7:0.3:1 (small SM emulsion), and a conventional emulsion with a diameter of about 250 nm and a composition of PC: soybean oil = 1:1 (large PC emulsion) were compared. Highly lipophilic [14C]cholesteryl oleate, a marker of emulsion particles, indicated diverse in vivo behaviors; i.e., the small SM emulsion produced prolonged circulation in the blood, and the small PC emulsion followed this, while the large PC emulsion was rapidly uptake by the liver. Thus, a reduction in size and coating with SM on the surface of oil droplets resulted in avoidance of the reticuloendothelial system (RES). Disposition profiles of other test compounds differed, depending on their lipophilicities: [14C]cholesterol showed disposition patterns in all formulations similar to those of [14C]cholesteryl oleate, but moderately lipophilic [3H]prostaglandin E1 and [3H]retinoic acid showed common disposition profiles, regardless of emulsion types, suggesting their rapid release from the emulsion carriers. These results suggest that small SM emulsion and large PC emulsion can act respectively as long circulating and liver targeting carriers for highly lipophilic drugs with log PC(oct) larger than 9.

Animals↗
PubMed1993

Controlled biodistribution of highly lipophilic drugs with various parenteral formulations.

Lipid carrier systems are considered effective for targeting highly lipophilic drugs, but little systematic information about the effect of the physicochemical and pharmaceutical characteristics of drugs and formulations on their performance has been obtained. 3H-Retinoic acid and 14C-cholesteryl oleate with different lipophilicities (log PCoct = 6.6 and 18, respectively) were selected as model drugs and the potential of formulations such as oil in water (o/w) emulsion, micellar solution, and liposomes for controlling their biodistribution was demonstrated. After intravenous injection in mice, 3H-retinoic acid showed similar disposition profiles irrespective of formulation type, suggesting its rapid dissociation from carriers. 14C-Cholesteryl oleate with extremely high lipophilicity revealed widely varied disposition profiles reflecting the distribution patterns of carriers: micellar solution and liposomes showed large AUC values and low hepatic clearances, while the use of emulsion as a carrier resulted in rapid clearance from blood circulation into the liver. The results suggested that these formulations can be used as targeting carriers for lipophilic drugs which, however, should have a sufficiently high lipophilicity of about log PCoct 9-16.

Animals↗