Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Members of the matrix metalloproteinase (MMP) family are responsible for breakdown of extracellular matrix components involved in morphogenetic remodeling of animal embryogenesis. The highly sensitive assay of MMP using synthetic fluorescence-quenching substrate was employed to detect and to characterize a veiled MMP activity expressed in Japanese flounder embryos undergoing formation of lenses. The MMP activity was enhanced in proportion to increasing protein amounts of the embryonic lysate over 5 microg, and this reaction was proceeded in a time-dependent manner and with increasing substrate concentrations. Almost 2-fold increase in the embryonic MMP activity occurred by treatment with 4-aminophenylmercuric acetate, but the activity was markedly suppressed by metal chelating reagents. These enzymatic characteristics are apparently consistent with those of mammalian embryonic MMPs, particularly MMP-9. The characterized MMP activity was highly expressed at the specificstage during embryogenesis, indicating that this MMP may be involved in formation of lenses.
Cell Mol Biol (Noisy-le-grand) 2000 Nov
PMID:Characterization of matrix metalloproteinase in flatfish embryo undergoing formation of lenses. 1107 55

Neointima formation after arterial de-endothelialization refers not only to smooth muscle cell (SMC) migration and proliferation, but also involves extracellular matrix (ECM) metabolism. Most studies regarding the role of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in neointima have focused on the early phase of vascular remodeling. In this study, we examined the expression of MMP and TIMP in rabbit aortic neointima at a relatively late stage of lesion development, between 4 and 12 weeks after initial de-endothelialization. Northern blot analysis revealed expression of steady-state MMP-9 mRNA was increased up to the 4th week and MMP-2 mRNA to the 12th week after de-endothelialization. In situ hybridization shown that MMP positive cells were predominantly distributed in arterial neointima. Expression of TIMP-1 mRNA was continuously up-regulated up to the 12th week and TIMP-1 positive cells, primarily SMCs, were also localized to the neointimal tissue. Alteration at mRNA level was accompanied by that at protein level, as assessed by SDS-PAGE zymography for MMPs and immunoblotting for TIMP-1. The profile of alteration at protein level correlated well with that at mRNA level. These data suggest that synthesis of MMPs and TIMP is a prolonged process and arterial SMC is a major source of MMP production in arterial neointima. Enhanced synthesis of MMPs and TIMPs at late stage of neointimal development may contribute to arterial ECM metabolism.
Int J Mol Med 2001 Jan
PMID:Expression of metalloproteinases and its inhibitor in later stage of rabbit neointima development. 1111 18

The involvement of leukotriene (LT) B(4) in the ovulatory process of the rat was investigated by the use of a LTB(4)-receptor antagonist (ZK158252 = L-ANT) administered either intrabursally in vivo or to the in-vitro perfused ovary. The in-vivo experiments revealed inhibition of human chorionic gonadotrophin (HCG)-induced ovulation by 500 micromol/l L-ANT (median 5.5, 25-75% range 1.0-6.0) compared with controls (median 9.0, range 6.25-13.5). In vitro, ovulation was induced by LH (0.2 microg/ml) + 3-isobutyl-1-methylxanthine (IBMX; 0.2 mmol/l). The ovary was perfused either for 20 h, to study ovulation rate, or for 10 h to examine ovarian concentrations of the ovulatory mediators matrix metalloproteinase (MMP)-2 and MMP-9, plasminogen activator (PA), prostaglandin (PG)E(2) and PGF(2 alpha). Addition of LH+IBMX resulted in a marked stimulation of steroid release and ovulations occurred in all ovaries (median 11.0, range 10.0-14.0). The L-ANT inhibited ovulation in a dose-dependent way (median 10.0, range 8.0-13.0 at 1 micromol/l; median 6.0, range 3.5-10.0 at 10 micromol/l; median 2.0, range 0.75-5.75 at 100 micromol/l). The intra-ovarian activity of PA was increased 1.5-fold by L-ANT (100 micromol/l), but the concentrations of PGE(2) and PGF(2 alpha) remained unaltered. While no changes in MMP-9 were observed, conversion from pro-MMP-2 to active MMP-2 was inhibited by L-ANT. These results suggest that activation of the LTB(4)-receptor within the ovary is involved in the ovulatory process and that the effects of LTB(4)-receptor activation are partly mediated via MMP-2.
Mol Hum Reprod 2001 Jan
PMID:Inhibition of ovulation in the rat by a leukotriene B(4) receptor antagonist. 1113 58

Polycystic ovarian syndrome (PCOS) involves follicular atresia, formation of multiple ovarian cysts and is frequently associated with a higher abortion rate. Follicular development, ovulation, formation of corpus luteum and its regression involve extensive tissue remodelling. Mammalian ovaries express a number of matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP). We assessed the differences in production of MMP-2, MMP-9 and TIMP-1 by cultured luteinized granulosa cells from women with PCOS and normal ovulatory women after ovarian stimulation for IVF treatment. In follicular fluid from women with PCOS, levels of MMP-9 and MMP-2 were higher than the normal group, as was the basal production of these proteins by cultured cells. Basal production of TIMP-1 by cultured cells was not different between PCOS and normal groups. A time-dependent increase in the production of MMP-9 was observed in cells from both normal and PCOS women, although the increase was more pronounced in the latter. Thus the MMP-TIMP balance is shifted toward greater MMP activity in luteinized granulosa cells from women with PCOS.
Mol Hum Reprod 2001 Apr
PMID:The balance between MMP-9 and MMP-2 and their tissue inhibitor (TIMP)-1 in luteinized granulosa cells: comparison between women with PCOS and normal ovulatory women. 1127 94

Human alveolar macrophages (AM) and lung tissue macrophages (LTM) have a distinct localization in the cellular environment. We studied their response to direct contact with activated T lymphocytes in terms of the production of interstitial collagenase (MMP-1), 92-kD gelatinase (MMP-9), and of TIMP-1, one of the counter-regulatory tissue inhibitors of metalloproteinases. Either AM obtained by bronchoalveolar lavage or LTM obtained by mincing and digestion of lung tissue were exposed for 48 h to plasma membranes of T lymphocytes previously activated with phorbol myristate acetate and phytohemagglutinin for 24 h. Membranes of activated T cells strongly induced the production of MMP-1, MMP-9, and TIMP-1 exclusively in LTM but not in AM, whereas membranes from unstimulated T cells failed to induce the release of MMPs. Both populations of mononuclear phagocytes spontaneously released only small amounts of MMPs and TIMP-1. Similar results were obtained when MMP and TIMP-1 expression was analyzed at pretranslational and biosynthetic levels, respectively. Blockade experiments with cytokine antagonists revealed the involvement of T-cell membrane-associated interleukin-1 and tumor necrosis factor-alpha in MMP production by LTM upon contact with T cells. These data suggest that the ability of lung macrophages to produce MMPs after direct contact with activated T cells is related to the difference in phenotype of mononuclear phagocytes and cell localization. In addition, these observations indicate that cell-cell contact represents an important biological mechanism in potentiating the inflammatory response of mononuclear phagocytes in the lungs.
Am J Respir Cell Mol Biol 2001 Apr
PMID:Human lung tissue macrophages, but not alveolar macrophages, express matrix metalloproteinases after direct contact with activated T lymphocytes. 1130 38

The CRE (cyclic AMP response element)-transcription factor complex plays a critical role in response to hormonal signals for cell proliferation, differentiation, and apoptosis. We have reported previously that the CRE-transcription factor decoy oligonucleotide specifically slows tumor cell proliferation and inhibits CRE- and Ap-1-directed transcription in vivo (Park et al., 1999). We have investigated the effect of inhibiting CRE-directed transcription on ovarian cancer cell growth. Here, we report that CRE-decoy oligonucleotide treatment results in the inhibition of cell growth and a marked reduction in the expression of the regulatory and catalytic subunits of protein kinase A and the type I and type II protein kinase A holoenzymes. Growth inhibition was accompanied by changes in cell morphology, appearance of apoptotic nuclei, and DNA fragmentation. In addition, MMP-9 (matrix methalloproteinase-9) activity was markedly reduced in CRE-decoy treated cells. Indirect immunofluorescence revealed that CRE-decoy oligonucleotide treatment promoted export of the CRE-binding protein, CREB, from the nucleus to the cytoplasm, while importing the catalytic subunit of protein kinase A from the cytoplasm to the nucleus. The results indicate that the decoy oligonucleotide, by binding specifically to CRE-transcription factors, interferes with CRE-directed transcription in vivo. These results show a critical role for CRE-directed transcription in ovarian cancer cell growth. Thus, the CRE-decoy oligonucleotide may provide a powerful means to combat ovarian cancer.
Mol Cell Biochem 2001 Feb
PMID:Apoptosis, growth arrest and suppression of invasiveness by CRE-decoy oligonucleotide in ovarian cancer cells: protein kinase A downregulation and cytoplasmic export of CRE-binding proteins. 1133 Aug 38

Matrix metalloproteinases (MMPs) are upregulated locally in sites of inflammation, including the lung. Several MMP activities are upregulated in acute lung injury models but the exact role that these MMPs play in the development of the lung injury is unclear due to the absence of specific inhibitors. To determine the involvement of individual MMPs in the development of lung injury, mice genetically deficient in gelatinase B (MMP-9) and stromelysin 1 (MMP-3) were acutely injured with immunoglobulin G immune complexes and the intensity of the lung injury was compared with genetically identical wild-type (WT) mice with normal MMP activities. In the WT mice there was upregulation of gelatinase B and stromelysin 1 in the injured lungs which, as expected, was absent in the genetically deficient gelatinase B- and stromelysin 1-deficient mice, respectively. In the deficient mice there was little in the way of compensatory upregulation of other MMPs. The gelatinase B- and the stromelysin 1-deficient mice had less severe lung injury than did the WT controls, suggesting that both MMPs are involved in the pathogenesis of the lung injury. Further, the mechanism of their involvement in the lung injury appears to be different, with the stromelysin 1-deficient mice having a reduction in the numbers of neutrophils recruited into the lung whereas the gelatinase B-deficient mice had the same numbers of lung neutrophils as did the injured WT controls. These studies indicate, first, that both gelatinase B and stromelysin 1 are involved in the development of experimental acute lung injury, and second, that the mechanisms by which these individual MMPs function appear to differ.
Am J Respir Cell Mol Biol 2001 May
PMID:Role of stromelysin 1 and gelatinase B in experimental acute lung injury. 1135 Aug 22

Chronic estrogen treatment results in elevated levels of the gelatinase pro-MMP-9 in the pituitary of tumor-susceptible Fischer 344 rats. In contrast, pituitary pro-MMP-9 level is not increased by estrogen treatment in rats of the tumor-resistant BN strain nor in rats of an F(1) hybrid of these strains. The gelatinase MMP-2 is also detected in rat pituitary, but its level is not affected by either estrogen or rat genotype. In 124 estrogen-treated rats from a backcross of the F(1) hybrid to the F344 strain, the levels of both monomer and dimer forms of pro-MMP-9 correlate with the tumor phenotypes mass, total DNA, and hemoglobin content of the pituitary. In this backcross, the QTL Edpm5 (_e_strogen-_d_ependent _p_ituitary _m_ass on Chromosome 5) has a significant effect on MMP-9 levels, with inheritance of the BN allele of Edpm5 correlating with suppression of estrogen-dependent MMP-9 expression.
Mol Cell Endocrinol 2001 May 15
PMID:Suppression of estrogen-dependent MMP-9 expression by Edpm5, a genetic locus for pituitary tumor growth in rat. 1136 54

Scar formation following adult spinal cord (SC) hemisection is accompanied by important remodeling of the surrounding extracellular matrix (ECM). Since ECM molecules provide the substrate for axon growth, these changes in ECM composition are likely to influence the process of axonal regeneration. Here we investigated whether scar formation could be associated with the activation of matrix metalloproteinases (MMPs), a class of proteins implicated in ECM remodeling thought to favor axonal regeneration in the peripheral nervous system. Two members of the MMP family, MMP-2 and MMP-9, were found to be transiently upregulated in the SC wound. In situ fluorescent zymography revealed a MMP-related gelatinase activity (GA) in the wound, which was spatially and temporally correlated with scar formation. The GA formed a striking pattern of interwoven pathways along which neurites were seen to grow. These pathways corresponded to the distribution of other ECM molecules, which are known to have antagonistic effects on axonal regrowth. Our results suggest that neurite ingrowth into the wound may transiently benefit from this ECM remodeling and, in particular, from the upregulation of MMPs.
Mol Cell Neurosci 2001 Jun
PMID:MMP-related gelatinase activity is strongly induced in scar tissue of injured adult spinal cord and forms pathways for ingrowing neurites. 1141 85

Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) are major regulators of tissue remodelling of the extracellular matrix (ECM) and may also be involved in the control of growth factor availability. We have investigated their production and localization in the developing human gonad during mid-gestation using zymographic techniques and immunohistochemistry. The secretion of MMP-2, MMP-9 and all four TIMP was demonstrated from both testis and ovary, with the predominant gelatinase produced by both being MMP-2. In the testis, MMP-1, MMP-2, MMP-9 and all TIMP family members were localized to the interstitium and to varying degrees within the tubules. MMP-9 and TIMP-4 were abundant in both Sertoli cells and gonocytes and MMP-1 and TIMP-1 were localized in particular to Sertoli cells. In the ovary, all TIMP and MMP-1, MMP-2 and MMP-9 were localized to the oogonium/oocyte cytoplasm with varying intensities and MMP-1, TIMP-2 and TIMP-3 were also detected in the ovarian stroma. This study demonstrates that MMP-1, MMP-2, MMP-9 and all TIMP family members are secreted by the developing ovary and testis and are localized to specific cell and tissue sites. MMP and TIMP are likely to play a role in ECM remodelling during gonadal development and also in the cell and matrix interactions that control a range of cellular functions.
Mol Hum Reprod 2001 Jul
PMID:Matrix metalloproteinases and tissue inhibitors of metalloproteinases in human fetal testis and ovary. 1142 Mar 87


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