Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A non-metastatic epithelial tumor cell line, OV3121, was established from ovarian granulosa cell tumor in B6C3F1 mouse irradiated with 60Co-gamma rays. OV3121 cells showed an epithelial morphology and grew in monolayer with a population doubling time of 28-30 h. The production of estradiol and the expression of cytokeratin confirmed the epithelial origin of the line. No pulmonary metastasis was observed from solid tumors after subcutaneous (s.c.) injection or after intravenous (i.v.) injection of a clonal subline, OV3121-1 cells. We examined the experimental metastasis of individual clones of OV3121-1 cells, containing various introduced viral oncogenes: v-Ha-ras, v-Ki-ras, v-fms, v-mos, v-raf, v-src, v-sis, v-fos and v-myc. Among them, only OV3121-1 cells with v-Ha-MuSV or v-Ki-MuSV produced lung colonies at high frequencies. In a more detailed analysis, the v-Ha-ras transfectants OV-ras4 and OV-ras7 were found to form colonies in various organs by metastasis from tumors after s.c. injection, as well as lung colonies after i.v. injection. Moderately metastatic OV-ras7 cells showed high gelatinolytic activity at 72 kDa (MMP-2) and 92 kDa (MMP-9) as compared with the parental OV3121-1 and OV-Neo control cells by zymographic analysis. However, more metastatic OV-ras4 cells produced progressively weaker bands of 72 kDa gelatinolytic activity. No gross alterations in the expression of MMP-1, MMP-3, TIMP-1 and TIMP-2 transcripts were detected in these cell lines. These results suggest that this ovarian granulosa cell tumor line may provide a useful system for understanding the mechanisms by which oncogenes influence the occurrence of metastasis.
...
PMID:A radiation-induced murine ovarian granulosa cell tumor line: introduction of v-ras gene potentiates a high metastatic ability. 777 56

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play a critical role in extracellular matrix homeostasis. We have previously cloned human and mouse TIMP-3 cDNAs and mapped their chromosomal loci (Apte, S. S., Mattei, M-G., and Olsen, B. R. (1994) Genomics 19, 86-90; Apte, S. S., Hayashi, K., Seldin, M. F., Mattei, M-G., Hayashi, M., and Olsen, B. R. (1994) Dev. Dynam. 200, 177-197); the identification of TIMP3 mutations in Sorsby's fundus dystrophy has underscored the functional importance of TIMP-3. We now report that TIMP-3 is encoded by five exons spanning over 30 kilobase pairs of mouse genomic DNA. In the attribution of protein domains to specific exons, as well as exon structures, the Timp-3 and Timp-1 genes are similar, confirming the common evolutionary origin of the TIMPs and defining a distinct gene family. We have expressed human and mouse TIMP-3 in mouse NSO myeloma cells. In each case, an N-glycosylated 27-kDa protein was generated, that, like TIMP-1 and TIMP-2, inhibited collagenase-1, stromelysin-1, and gelatinases A and B. TIMP-3 and TIMP-1 inhibition were quantitatively similar, implying that all TIMPs are equally efficient in MMP inhibition. Instead, differential regulation of the TIMP genes or divergent C-terminal protein sequences may underlie distinct biological functions for each TIMP.
...
PMID:The gene structure of tissue inhibitor of metalloproteinases (TIMP)-3 and its inhibitory activities define the distinct TIMP gene family. 857 69

The truncated forms of tissue inhibitor of metalloproteinase-1 and -2 (delta TIMP-1 and -2), comprising the N-terminal active domain, are ideal molecules for structural analysis by intrinsic fluorescence as each contains a single conserved tryptophan residue. In this paper we describe studies on their conformational stability, unfolding/refolding kinetics and the environment of the unique tryptophan as judged by its fluorescence properties in the native state and exposure to an external quencher, acrylamide. Two forms of delta TIMP-2 were studied: delta TIMP-2 T21 derived from the full-length cDNA clone isolated from a mixed-tumour library, and delta TIMP-2 A21 containing the highly conserved V18IRAK22 sequence. In all three delta TIMP proteins the tryptophan environments in the native state appeared to be similar, but substantial differences were seen in their conformational stabilities and refolding kinetics. delta TIMP-1 was approximately twice as stable as delta TIMP-2 T21 and 1.4-fold more stable than delta TIMP-2 A21. This stability difference between delta TIMP-1 and delta TIMP-2 was shown to be independent of N-linked glycosylation. delta TIMP-1 and delta TIMP-2 A21 both showed simple two-state refolding kinetics, whereas delta TIMP-2 T21 refolding was more complex and biphasic in character. These differences between delta TIMP-2 T21 and A21 suggest that residue 21 is a structurally important site in the TIMP protein. All three truncated molecules can be considered as stable independent folding domains ideally suited for further structural analysis.
...
PMID:Folding and stability of the active N-terminal domain of tissue inhibitor of metalloproteinases-1 and -2. 780 30

The present study was designed to assess whether expression of mRNA for extracellular matrix (ECM) components, metalloproteinases (MMP) and tissue inhibitor of metalloproteinases (TIMP) in glomeruli is affected by a low protein diet during the course of focal glomerulosclerosis (FGS). Puromycin aminonucleoside (PAN) was injected intraperitoneally in rats and the right kidney was removed on day 22. Nephrotic rats received successive intraperitoneal injections of PAN on days 27, 34, and 41. Control rats were subjected to a nephrectomy or a sham operation on day 22. Animals were divided into six groups. In group 1, the PAN-injected rats were fed a standard diet containing 22% protein. In group 2, the PAN-injected rats were fed a low protein diet containing 6% protein, starting on the same day as the first PAN injection. In group 3, the nephrectomized rats without PAN were fed a standard diet. In group 4, the nephrectomized rats without PAN were fed a low protein diet for the same period. In group 5, the sham operated rats were fed a standard diet. In group 6, the sham operated rats were fed a low protein diet for the same period. Rats were sacrificed on days 0, 60 or 80 after the initial PAN or saline injection. The percentage of sclerotic glomeruli in group 1 rats increased markedly with time, reaching 77% on day 80. The mRNA levels encoding for alpha 1(I), alpha 1(III), alpha 1(IV) collagen chains, laminin B1 and B2 chains, heparan sulfate proteoglycan (HSPG), MMP-2, TIMP-1 and TIMP-2 increased significantly as glomerulosclerosis progressed, whereas MMP-1 and MMP-3 mRNA levels were unchanged, and no MMP-9 mRNA was detected throughout the experiments. In group 2, the low protein diet reduced the prevalence of glomerulosclerosis and attenuated the increased mRNA expression for ECM components, MMP-2, TIMP-1 and TIMP-2 in FGS glomeruli. In groups 3 through 6, mRNA levels for ECM components decreased with age, whereas those for MMPs and TIMPs changed little throughout the experiments. Immunofluorescence studies revealed the accumulation of types I, III and IV collagens, laminin, and HSPG in the sclerotic area and low protein diet attenuated the accumulation of these proteins. These data suggest that glomerulosclerosis may result from an imbalance among ECM components, MMPs and TIMPs and that a low protein diet attenuates the otherwise increased levels of mRNA for ECM components, MMP-2, TIMP-1 and TIMP-2 in glomerulosclerosis.
...
PMID:Low protein diet blunts the rise in glomerular gene expression in focal glomerulosclerosis. 793 7

Hyperlipidemia, especially hypercholesterolemia, may contribute to glomerulosclerosis as it does to atherosclerosis. Low density lipoprotein (LDL) stimulates the production of extracellular matrix by mesangial cells in culture as well as the proliferation of mesangial cells. This study was carried out to examine the effects of LDL on the type IV collagen (CIV) production by cultured rat mesangial cells (CRMC). Subconfluent CRMC monolayers which were grown in RPMI with 20% lipid-free fetal calf serum for 48 h were challenged with LDL (0, 50, 100, 150 and 200 micrograms/ml) for another 48 h. LDL was prepared from normal human plasma. Mesangial cell proliferation was examined by [3H]-thymidine uptake. Production of CIV was evaluated as the expression of CIV on the cell surface by flow-cytometric analysis. The collagen synthesis was measured by the [3H]-proline uptake. Total RNA was extracted from CRMC at 6 and 24 h of incubation with 150 micrograms/ml LDL, and Northern blotting and hybridization was performed with cDNAs for alpha 1-CIV, for 72-kD collagenase and for tissue inhibitor of metalloproteinase (TIMP)-2. The amount of total mRNA was corrected with beta-actin mRNA. Mesangial cell proliferation increased in all concentrations studied and had a peak value of 221% with 150 micrograms/ml of LDL. Expression of CIV increased by 30-60% in 100-200 micrograms/ml of LDL. Collagen synthesis also increased by 50-70% in 150-200 micrograms/ml of LDL. The mRNA ratio (procollagen alpha 1(IV)/beta-actin) increased to 133% at 24 h. The mRNA ratio (TIMP-2/beta-actin) increased to 137% at 24 h. mRNA ratios at 6 h showed no change.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Effects of low density lipoprotein on type IV collagen production by cultured rat mesangial cells. 793 24

The characterization and regulation of matrix metalloproteinases (MMPs) have been studied to determine their role(s) in periodontal tissue destruction. Progress in elucidating the roles of MMPs in periodontal tissue destruction has led to a new concept involving the chemotherapeutic inhibition on MMPs, a therapeutic strategy which less than a decade ago was considered "a difficult and perhaps impossible task." Tetracyclines/doxycycline (DOXY) and their chemically modified nonantimicrobial derivatives (CMTs) are known to inhibit the matrix metalloproteinases, especially preferring human neutrophil collagenase (MMP-8), and prevent the oxidative activation of procollagenases. We characterized by Western blotting the molecular forms and cellular sources of gingival tissue, dental plaque, gingival crevicular fluid (GCF), and salivary MMPs associated with periodontitis. Also the molecular forms of tissue inhibitors of matrix metalloproteinases (TIMP-1 and TIMP-2) in periodontitis were studied by Western blot. Neutrophil (PMN)-derived MMPs were found to predominate in periodontitis, and phospholipase C present in increased amounts in periodontitis sites was found to be a potential inducer of PMN degranulation. We further studied the effects of DOXY on molecular forms of different latent and active MMPs purified from different cellular sources (PMNs, fibroblasts, keratinocytes) and present in vivo in oral exudates (gingival extracts, GCF, and saliva). DOXY inhibition of activated (oxidatively or proteolytically) MMPs were not associated with MMP fragmentation. Michaelis-Menten plots of initial rates of degradation of soluble type I collagen revealed an apparent Km value of 0.3-0.6 microM for MMP-8, and 75 microM DOXY inhibited MMP-8 in a manner which did not result in changes in apparent Km value but did prevent the initial degradation reaching Vmax providing evidence for noncompetitive inhibition. Treatment of patients with long-term DOXY medication results in decreased MMP-8 activities/levels in gingival tissue, crevicular fluid, and saliva, but not fragmentation of MMP-8 in vivo. These data further support and extend the key role of PMN-MMPs in periodontitis, and the activities of these PMN MMPs can be inhibited directly by therapeutic levels of DOXY.
...
PMID:Effects of tetracyclines on neutrophil, gingival, and salivary collagenases. A functional and western-blot assessment with special reference to their cellular sources in periodontal diseases. 797 85

Chronic pancreatitis is characterized by proliferation of the extracellular matrix and by increased deposition of interstitial extracellular matrix proteins (collagens type I and III, fibronectin). In this study we analyzed the balance of expression of mRNAs encoding extracellular matrix components (collagens I, III and IV, laminin, fibronectin), extracellular matrix degrading metalloproteinases (MMP-1, -2 and -3) and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in chronic pancreatitis (n = 8) and control pancreas (n = 7) by northern blot analysis. Transcripts for MMP-1 (interstitial collagenase), MMP-3 (stromelysin) and TIMP-1 were not detectable in chronic pancreatitis and control tissues. Steady-state levels of transcripts encoding extracellular matrix proteins, MMP-2 (72 kDa collagenase IV) and TIMP-2 were enhanced in 7 out of 8 chronic pancreatitis tissue samples and showed a large degree of variation between individual patients. Transcript levels could not be correlated to the histologically detectable degree of inflammation and fibrosis or to the total amount of deposited collagen protein, which was high in all chronic pancreatitis tissue samples as determined by a standard colorimetric procedure. Increased steady state levels of transcripts encoding extracellular matrix proteins or extracellular matrix degrading proteases may thus reflect the activity of processes involved in the remodeling of the gland during chronic inflammation. The precise role of overexpression of MMP-2 and its inhibitor TIMP-2 will have to be elucidated in further studies.
...
PMID:Balance of expression of genes coding for extracellular matrix proteins and extracellular matrix degrading proteases in chronic pancreatitis. 801 97

Gelatinase activity and inhibitory activity against collagenase were measured in serum-free medium conditioned by murine colonic carcinoma cells with different spontaneous metastatic potentials to the lung. The medium conditioned with poorly metastatic NM11 cells gave higher inhibitory activity than that conditioned with highly metastatic LuM1 cells, while the level of secreted gelatinases in the same medium was lower in NM11 medium than in LuM1 case. Northern analysis showed the higher gene expression of both tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 in NM11 cells than in LuM1 cells, suggesting that both TIMPs are responsible for the increase of inhibitory activity in NM11 conditioned medium. Examination of the balance of gelatinases and inhibitor revealed that the amount of inhibitor exceeded that of gelatinases in the medium conditioned with NM11 cells. In contrast, the medium conditioned with LuM1 cells contained excess amounts of gelatinases. The results indicated a close correlation between the balance of gelatinases and inhibitors and the metastatic behavior of murine tumor cells.
...
PMID:Gelatinases and metalloproteinase inhibitor secreted by murine colonic carcinoma cells with differing metastatic potential. 801 90

The expression and regulation of 72-kDa gelatinase and TIMP-2 were examined in cultures of early and late passage human fibroblasts. In contrast to collagenase expression, which was low in early passage cells and highly expressed in late passage fibroblasts, 72-kDa gelatinase mRNA expression was enhanced only slightly in late passage cultures and 72-kDa gelatinase protein expression was similar in early and late passage cultures. In contrast to published reports of decreased TIMP-1 expression, TIMP-2 mRNA and protein were increased in late passage cells. Exposure to Il-1 alpha increased the steady-state level of 72-kDa gelatinase mRNA by 3x in early passage cells but had no effect on late passage cells. Although Il-1 alpha had no significant effect on TIMP-2 mRNA or on expression of 72-kDa gelatinase, in either early or late passage cells, Il-1 alpha increased the level of a TIMP-2-72-kDa gelatinase complex. Using monoclonal antibodies to TIMP-2 and to 72-kDa gelatinase we detected two forms of TIMP-2. One form was complexed to 72-kDa gelatinase and migrated with an apparent molecular weight of 72 kDa and the other migrated at the expected molecular weight of 21 kDa. Autoradiography in conjunction with Western analysis confirmed that in the late passage cell medium the newly synthesized 72-kDa gelatinase-TIMP-2 complex was increased even though the expression of 72-kDa gelatinase did not change. The present results establish that the regulation of 72-kDa gelatinase and TIMP-2 in early and late passage cultures of human fibroblasts are different from collagenase and TIMP-1 regulation. Further, they establish that in late passage cultures the activity of 72-kDa gelatinase may be regulated through the formation of a denaturation-resistant complex.
...
PMID:Expression of 72-kDa gelatinase and TIMP-2 in early and late passage human fibroblasts. 802 May 85

Death from cancer results from the development of metastases or local progression of tumour. Metastasis and local progression may result from the inappropriate activity of metalloproteinases released by tumour cells or of their regulatory peptides. We have developed quantitative assays for interstitial collagenase, stromelysin 1 and tissue inhibitors of metalloproteinase (TIMP) 1 and 2, which have allowed the study of serum levels of these proteins. Sera from 40 patients with prostatic cancer, stored prior to and after 6 and 12 months' treatment with a gonadotrophin-releasing hormone agonist and an anti-androgen were analysed. Levels were compared with two control groups, comprising 21 patients with active rheumatoid arthritis and 56 age-matched hospital attenders without arthritis or cancer. Contrasting levels have been found in patients with prostatic cancer as compared with hospital controls without cancer and patients with rheumatoid arthritis. Patients with prostatic cancer had higher levels of TIMP-1 and collagenase (P = 0.0001) and lower levels of TIMP-2 (P = 0.003) than controls. Patients with metastatic cancer had significantly higher levels of collagenase than those without metastases (P = 0.02). Patients with rheumatoid arthritis had significantly higher levels of stromelysin than either controls (P = 0.002) or patients with cancer (P = 0.008). Serum tissue inhibitor of metalloproteinase 1 in combination with collagenase levels was as sensitive as prostate-specific antigen as a marker of metastatic disease. These findings provide a basis for the investigation of the role of metalloproteinases and their inhibitors in other malignancies.
...
PMID:Serum metalloproteinases and their inhibitors: markers for malignant potential. 808 Jul 38


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---