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

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

This study quantifies the parenchymal and nonparenchymal uptake of technetium-99m (99mTc)- and indium-111 (111In)-low-density lipoprotein (LDL) in different states of hepatic LDL-receptor activity to validate quantitative LDL scintigraphy. Iodine-125 (125I)-LDL was used as reference tracer. Four Sprague-Dawley rats with 17-alpha-ethinyl estradiol (EE)-stimulated LDL-receptor activity and five controls received all three tracers simultaneously 90 minutes before collagenase liver perfusion and metrizamide gradient cell separation. Total liver uptake of 99mTc-, 111In-, and 125I-LDL was 1.8 +/- 1.0, 1.6 +/- 0.8, and 0.2 +/- 0.2% injected dose/g organ weight, respectively. The contribution of nonparenchymal cells to total hepatic tracer uptake was 5.4 +/- 4.7%, 11.6 +/- 10.3%, and 9.6 +/- 7.6% in controls. Estradiol treatment increased total liver uptake to 2.4 +/- 0.5, 2.0 +/- 0.2, and 0.5 +/- 0.3% injected dose/g and reduced nonparenchymal cell contribution to 2.3 +/- 2.6%, 4.2 +/- 4.8%, and 2.6 +/- 2.9%, respectively. Dual-isotope scintigraphy in EE-treated and control rats confirmed these data, with a lower total hepatic uptake of 111In-LDL in comparison with 99mTc-LDL but a comparative degree of increase by EE treatment. Both behave quantitatively comparable as residualizing tracers, yet 99mTc-LDL shows a higher affinity to the LDL receptor pathway of parenchymal cells. However, the nonspecific uptake of both tracers can be neglected for quantitative LDL scintigraphy, and external imaging of hepatic tracer uptake primarily reflects LDL-receptor activity of parenchymal cells.
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PMID:Parenchymal and nonparenchymal uptake of technetium-99m, indium-111, and iodine-125 low-density lipoprotein in the normal and estradiol-stimulated rat liver: tracer validation for quantitative low-density lipoprotein scintigraphy. 755 83

Estrogen can effectively prevent estrogen deficiency-induced bone loss in animals and humans. However, its mechanism remains unknown. Osteoblast-derived Matrix metalloproteinse-1 (MMP-1), MMP-2, and tissue inhibitor of metalloproteinase-1 (TIMP-1) recently were implicated as playing important roles in initiating bone resorption. Therefore, we tested the effects of 17beta-estradiol (E2) on MMP-1, MMP-2, and TIMP-1 production in cultures of human osteoblastic MG-63 cells and normal human osteoblasts (hOB). MMP-1, MMP-2 and TIMP-1 concentrations in the culture medium were determined by ELISA, and activity of MMP-2 was assessed by ELISA. After 12-48 h of treatment, E2 at 10(-8)M decreased MMP-1 level in cultures of MG-63 cells or hOB. Treatment with increasing, dose of E2 in MG-63 cells or hOB caused a dose-dependent decrease in MMP-1 synthesis. E2 had no influence on MMP-2 and TIMP-1 production in MG-63 cells or hOB cultures, as well as activation of latent MMP-2. In conclusion, E2 represses MMP-1 synthesis, and this effect may contribute to its action on the inhibition of bone resorption, followed by prevention of bone loss. Increasing MMP-1 production followed by estrogen deficiency may contribute to the mechanisms involved in postmenopausal osteoporosis.
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PMID:Effects of 17beta-estradiol on the expression of matrix metalloproteinase-1, -2 and tissue inhibitor of metalloproteinase-1 in human osteoblast-like cell cultures. 1176 2

Estrogen receptors (ERs) efficiently potentiate the transcriptional activity of prolactin-activated Stat5b through a mechanism that involves the ER DNA-binding domain (DBD) and the hinge domain. We have identified residues within the DBD of ER that are critical for the functional interaction of ER with Stat5b. We show that disruption of the second zinc finger structure abrogated cross-talk between ER and Stat5b, while the structure of the first zinc finger was not important. Furthermore, we confirm that intact DNA binding activity was not required for potentiation of Stat5b activity and that the dimerization of ER did not seem to be involved. Ligand-bound ERs also modulated activating protein 1-dependent transcription, and our data demonstrate that both zinc finger structures of the ER DBD are important for an intact response. We show that introduction of various point mutations within the DBD altered the response of the receptor to 17beta-estradiol and to the estrogen antagonists 4-hydroxytamoxifen and ICI 182,870 on the collagenase promoter. These findings provide new insights into the mechanisms by which ERs act in cross-talk with non-related transcription factors.
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PMID:Mutations in the estrogen receptor DNA-binding domain discriminate between the classical mechanism of action and cross-talk with Stat5b and activating protein 1 (AP-1). 1241 47

The aim of this study was to evaluate the effect of estrogen on matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, and tissue inhibitor of metalloproteinase (TIMP)-1 in osteoarthritic chondrocytes. Chondrocytes from the knee cartilage of 25 postmenopausal osteoarthritic (OA) patients were cultured under various conditions: 0 pg/mL, 50 pg/mL, 500 pg/mL, and 5,000 pg/mL of 17beta-estradiol, with or without 10-1,000 pg/mL of either interleukin (IL)-1beta or tumor necrosis factor alpha (TNFalpha). MMP-1, MMP-3, MMP-13, and TIMP-1 in the conditioned media were analyzed with immunoblot or enzyme-linked immunosorbent assay (ELISA). Type II collagenolytic activity was measured by fluorogenic type II collagenolytic activity assay. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) using SYBR Green I dye was performed for the quantification of mRNA. Without cytokine stimulation, the secretion of MMP-1 was significantly reduced by 50 pg/mL of 17beta-estradiol (in immunoblot by a median of 12.3%, P=0.007; in ELISA by a median of 18.4%, P=0.001), and 500 pg/mL (in immunoblot by a median of 23.1%, P=0.001; in ELISA by a median of 21.0%, P=0.001). Additionally, under 10 pg/mL TNFalpha, 17beta-estradiol also significantly suppressed the secretion of MMP-1 (in immunoblot by a median of 39.0%, P=0.016; in ELISA by a median of 38.4%, P=0.041). Estrogen did not exert any significant effect on MMP-3, MMP-13, or TIMP-1 expression. With IL-1beta or TNFalpha above 10 pg/mL stimulation, 17beta-estradiol demonstrated no effect on MMP-1, MMP-3, MMP-13, or TIMP-1 secretion. Type II collagenolytic activity in the 50 pg/mL estradiol group decreased by 9.6% (-51.5-5.5%, P>0.05). 17beta-estradiol showed a tendency to decrease in MMP-1 mRNA. Estrogen may improve the imbalance between the amounts of MMPs and TIMP in chondrocytes, and these results suggest that hormone replacement therapy may provide some chondroprotective effect.
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PMID:Effect of estrogen on the expression of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 and tissue inhibitor of metalloproternase-1 in osteoarthritis chondrocytes. 1268 36

Estrogen plays an important role in maintaining normal bone metabolism via the direct or indirect regulation of bone cells. Osteoblastic cells, as the target cells of estrogen, can secrete multiple matrix metalloproteinases (MMPs) that participate in bone remodeling. It has been demonstrated that bone loss induced by estrogen deficiency is closely related to the abnormal expression of multiple MMPs in osteoblastic cells. However, the regulating action of estrogen on the expression of interstitial collagenases MMP-8 and MMP-13 in osteoblastic cells in vivo remains unclear. We used an ovariectomized osteoporotic rat model to analyze the changes in the histomorphometric parameters of bone after and without treatment with 17beta-estradiol (E(2)); We also used immunohistochemistry and in situ hybridization to observe changes in the expression of mRNA and the proteins MMP-8, MMP-13 and TIMP-1 in osteoblastic cells in rat proximal tibia. In this study, we found that in the ovariectomized rat the expression of MMP-13 mRNA and protein increased markedly, whereas the expression of MMP-8 and TIMP-1 mRNA and protein did not change significantly. Our analysis showed that the expression of MMP-13 protein was correlated positively to bone trabecular separation, osteoid surface area, and negatively to trabecular numbers and the percentage of trabecula bone volume/total tissue volume. Our results suggest that MMP-13 plays an important role in estrogen deficiency-induced bone loss, while estrogen can inhibit bone resorption and reduce bone turnover rate by down-regulating the expression of MMP-13 in osteoblastic cells.
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PMID:Effects of 17 beta-estradiol on the expression of interstitial collagenases-8 and -13 (MMP-8 and MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in ovariectomized rat osteoblastic cells. 1560 84

17beta-estradiol reduces cell death after global and focal ischemia and subarachnoid hemorrhage in rodents. Presently, we tested whether estrogen improves outcome after intracerebral hemorrhage (ICH) in male rats. Rats were implanted subcutaneously with 0.05, 0.25, or 0.50 mg pellets of estrogen (21-day release) or subjected to a sham procedure. Two weeks after implantation, they were given a striatal ICH via an infusion of collagenase. The three estrogen groups had significantly smaller lesions at a 7-day survival. Some rats had core temperature measured with an implanted telemetry probe, which also measured whole-body movements. Estrogen did not affect temperature nor activity levels after ICH. A second study with 0.25 mg pellets, administered once or twice, showed persistent histologic protection (30 days) and some functional benefit (e.g., elevated beam). A spectrophotometric hemoglobin assay showed that the 0.25 mg dose significantly reduced hemorrhagic blood volume at 12 hours after ICH. Regardless, estrogen did not lessen cerebral edema at 2 days after ICH and functional benefits were not consistently found on all tests (e.g., cylinder task). In summary, estrogen pretreatment reduces injury after ICH, in part by reducing bleeding. Estrogen may thus lessen injury and improve outcome after ICH in humans.
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PMID:17beta-Estradiol pretreatment reduces bleeding and brain injury after intracerebral hemorrhagic stroke in male rats. 1567 26

Estrogen influences not only the incidence of stroke, but also the amount of injury sustained from a stroke including intracerebral hemorrhage (ICH). In this study we tested whether delayed 17beta-estradiol (E2) treatment affects recovery following striatal ICH. Female rats were trained and tested on several behavioral tests to assess skilled reaching, spontaneous forelimb usage and walking ability. Two weeks following ovariectomy, rats were subjected to a moderate-sized ICH via infusion of collagenase into the striatum. One week later they were implanted with either an E2 pellet (0.36 mg; 60-day release) or they underwent a sham procedure. They were further divided into groups that received either environmental enrichment (EE) rehabilitation therapy (group housing in a complex cage with ramps, tunnels, etc.) or a control condition (group housing in a standard cage). Rats were then behaviorally evaluated out to 8 weeks post-ICH and then euthanized. Neither EE nor E2 affected lesion size, which averaged 62.8 mm(3) across all groups. The EE therapy improved recovery on some tests (e.g., traversing a horizontal ladder) whereas E2 treatment did not notably affect either spontaneous or EE-facilitated recovery. Thus, E2 fails to improve recovery or protect against brain injury when given after a 1-week delay in contrast to its clear neuroprotective effects when given before or soon after ICH.
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PMID:Failure of estradiol to improve spontaneous or rehabilitation-facilitated recovery after hemorrhagic stroke in rats. 1817 74

Estrogen receptors (ER) are present in connective tissues and therefore it is possible that the loss of estrogen after menopause influences the integrity of these tissues, contributing to development of degenerative conditions such as osteoporosis and osteoarthritis in a subset of women. Aberrant expression of matrix metalloproteinases (e.g. MMP-1 and MMP-13) has been implicated in the progression of these diseases. The present study investigated potential molecular mechanisms involved in the regulation of expression of MMP-1 and MMP-13 promoter variants by ER-alpha and ER-beta (+/-estrogen) in a transient transfection system. The results demonstrate that the activity of human MMP-1 and MMP-13 polymorphic variants is elevated in the presence of ER-alpha and ER-beta, and the single nucleotide polymorphisms present in the promoters of MMP-1 and MMP-13 variants leads to differential activities in response to the ER isoforms. Furthermore, the influence of 17-beta estradiol also varies depending upon whether the alpha or the beta isoform of ER is the modulator of these polymorphic variants. These findings support the conclusion that ER isoforms may be contributing to disease development and/or progression in genetically distinct subsets of women following menopause, and provide mechanistic insights into how such contributions are manifested.
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PMID:Polymorphisms in the promoter regions for human MMP-1 and MMP-13 lead to differential responses to the alpha and beta isoforms of estrogen receptor and their ligand in vitro. 1835 46

There is impaired wound healing and loss of type I collagen in skin aging, which can be improved by topical estrogen in vivo. The goal of this study was to determine the effects of estrogen, and progesterone and a combination of estrogen and progesterone as well, on the proliferation and the expression of type I collagen and matrixmetalloprotienase-1 (MMP-1, degrades collagen) in dermal fibroblasts (cells that synthesize collagen and MMP-1) in-vitro. Estrogen, progesterone, and its combination similarly and significantly inhibited cell proliferation and MMP-1 protein levels, and simultaneously stimulated type I collagen expression in the fibroblasts, indicating beneficial modulation.
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PMID:Beneficial regulation of type I collagen and matrixmetalloproteinase-1 expression by estrogen, progesterone, and its combination in skin fibroblasts. 2360 18


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