Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent work from this laboratory has shown that macrophages in culture synthesize and secrete a soluble factor(s) that induces the synthesis of collagenase in primary cultures of rabbit chondrocytes (Arth. Rheum. 23, 448, 1980). The current studies were undertaken to determine the role of arachidonate metabolism in this process. Incubation of chondrocytes with MCM (Macrophage Conditioned Medium) and low doses of indomethacin (1-10 microM) had no effect on collagenase synthesis. The lipoxygenase inhibitor NDGA, indomethacin at high doses (50 microM), diethylcarbamazine and the phospholipase inhibitor dibromoacetophenone, inhibited the MCM dependent synthesis of collagenase in chondrocytes. These inhibitors did not affect collagenase activity nor did they interfere with the activation of latent collagenase. Our data indicate that although cyclooxygenase plays no role in the MCM dependent induction of collagenase in chondrocytes, lipoxygenase activity may be essential.
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PMID:Studies on the effects of cyclo-oxygenase and lipoxygenase inhibitors on the macrophage stimulated synthesis of collagenase by rabbit chondrocytes. 300 57

Hereditary and acquired renal cysts develop from tubule segments that enlarge progressively. We measured the deformability of basement membranes surrounding individual normal tubules and cysts to determine if cysts might develop by simple extension of abnormally-deformable basement membrane in response to normal or increased transtubule hydrostatic pressures. Deformability (cm/dyne) was measured in individual tubules and cysts in vitro by a micropipet aspiration technique that related negative pressures within the pipet to the distance the tubule or cyst wall was aspirated into the pipet. Viscoelastic creep was determined from the time-dependent effect of pipet aspiration on membrane deformation. Proximal and collecting tubules, glomerular capsules and cysts were microdissected from controls and animals with acquired (Diphenylthiazole [rats]. Nordihydroguaiaretic acid [rats]), hereditary (C57 BL/6J [cpk/cpk] mice) and spontaneous (CFWw mice) renal cystic diseases. The major resistance to deformation was localized to the basement membrane since collagenase destroyed the elasticity of tubule and cyst walls. Tubule basement membranes adjacent to cysts appeared abnormal by electron microscopy in the animals fed DPT, but measurements of deformability and viscoelastic creep showed no differences between normal and cystic tubules in any animal model. Deformability values of cysts (7.7 +/- 1.1, 10.9 +/- 1.1, 11.2 +/- 0.6, 9.4 +/- 0.8 X 10(-3) cm/dyne in DPT, NDGA, C57 BL/6J and CFWw, respectively) are consistent with the interpretation that high transtubule pressures ranging from 39 to 134 cm H2O would be required if cysts form by simple stretching of the basement membrane secondary to a transepithelial hydrostatic pressure-gradient. Since in vivo measurements of hydrostatic pressures across cyst walls are not high enough we conclude that cysts do not enlarge due to increased deformability of tubule basement membranes.
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PMID:Viscoelastic properties of tubule basement membranes in experimental renal cystic disease. 365 32

Ovulation, recurring every midcycle of the mammalian female and triggered by a surge of luteinizing hormone (LH) released from the pituitary, is an essential prerequisite for fertilization and subsequent embryonic development. Here we shall describe two of the biological components of the ovulatory response, cumulus expansion (frequently denoted as cumulus maturation) and the rupture of follicular wall, both crucial for the release of a fertilizable ovum. The role of a proteolytic cascade and its regulation by eicosanoids will be emphasized in relation to follicle rupture. The new data implicating cumulus maturation as an essential step for the release of the ovum and the apparent mediatory role of interleukin-1 in this process will be presented. LH/hCG stimulates, in the preovulatory follicles, a cascade of proteolytic enzymes, including plasminogen activator (PA), plasmin and matrix metalloproteinase 1 (MMP-1). These enzymes bring about the degradation of perifollicular matrix and, most notably, the decomposition of the meshwork of collagen fibers which provides the strength to follicular wall. Furthermore, pharmacological blockage of any of these enzymes resulted in inhibition of follicle rupture. LH/hCG stimulates, in addition, an increase in ovarian production of eicosanoids. These include prostaglandins, obtained from arachidonic acid via the cyclooxygenase pathway and leukotrienes, the products of lipoxygenase. Previous studies from our and other laboratories have demonstrated the ability of inhibitors of cyclooxygenase and of lipoxygenases to suppress ovulation in several mammalian species. MK-886, which inhibits the translocation of 5-lipoxygenase (5-LO) from the cytosol and its binding to the membranal 5-LO activating enzyme, suppressed dose-dependently follicular rupture from the treated ovary. Zymographic analysis of ovarian extracts from PMSG/hCG-stimulated rats revealed a band of collagenolytic activity at 52kD, corresponding to human MMP-1 and at 72kD, corresponding to human MMP-2. Both activities were markedly stimulated by administration of hCG and were significantly inhibited by indomethacin, NDGA or MK-886. Thus, eicosanoids seem to mediate LH stimulation of follicular collagenase. Interleukin-1 (IL-1) has been recently implicated in ovulation. The ability of an IL-1 receptor antagonist (ra) to block ovulation in vivo and in vitro has been demonstrated recently. Morphological examination of the ovulatory follicles failing to ovulate suggests that this effect is exerted by inhibiting cumulus oophorus expansion and detachment from mural granulosa cells. In vitro, IL-1ra attenuated the action of hCG and FSH on cumulus expansion and follicular hyaluronic acid synthesis. Thus, IL-1 seems to mediate and/or facilitate gonadotropin action on cumulus expansion, and hence on ovulation.
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PMID:Ovulation as a tissue remodelling process. Proteolysis and cumulus expansion. 748 19

We have previously reported that hydrogen peroxide, an active oxygen species and a cellular oxidant, induces c-Fos and c-Jun mRNA expression and DNA synthesis in vascular smooth muscle cells and that these events require arachidonic acid release and metabolism through the lipoxygenase pathway. Here we have identified the eicosanoids that mediate the hydrogen peroxide-induced growth-related events in these cells. Hydrogen peroxide stimulated the production of 12- and 15-hydroperoxyeicosatetraenoic acids in vascular smooth muscle cells. Both 12- and 15-hydroperoxyeicosatetraenoic acids induced the expression of c-Fos and c-Jun protein and increased activating protein 1 (AP-1) activity, as measured by AP-1-DNA binding and AP-1-dependent human collagenase promoter-driven chloramphenicol acetyltransferase reporter gene transcription. Hydrogen peroxide and arachidonic acid also induced the expression of c-Fos and c-Jun protein and AP-1 activity. Nordihydroguaiaretic acid, an inhibitor of the lipoxygenase pathway, significantly inhibited both hydrogen peroxide and arachidonic acid-stimulated c-Fos and c-Jun protein expression and AP-1 activity. Together, these findings suggest that hydrogen peroxide induces the production of eicosanoids and that the eicosanoids are potential mediators of the oxidative stress-stimulated growth-related events in vascular smooth muscle cells.
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PMID:Role of hydroperoxyeicosatetraenoic acids in oxidative stress-induced activating protein 1 (AP-1) activity. 891 Mar 70