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)

The incorporation of methionine, lysine, and leucine into protein was studied in Ca2+-depleted and Ca2+-restored preparations of C-6 glial tumor cells in minimal medium. Although incorporation proceeded at linear rates in both preparations for more than 1 h and into the same spectrum of proteins, Ca2+-restored cells incorporated amino acid 5- to 10-fold more rapidly than Ca2+-depleted cells. Addition of approximately 200 microM Ca2+ in excess of chelator was required to achieve maximal rates of incorporation in Ca2+-depleted preparations. Stimulation by Ca2+ was rapid in onset (several minutes) and slowly reversible by chelator. Ca2+ was uniquely potent and specific among physiologically occurring cations in conferring such stimulation. Stimulation of amino acid incorporation by Ca2+ occurred over a broad range of pH and osmolarities and was facilitated by Mg2+. The effects of Ca2+ in stimulating amino acid incorporation were not traceable to changes in cAMP metabolism, amino acid uptake, protein catabolism, cell ATP or GTP content, or aminoacylation of transfer RNA. Actinomycin D (1 microgram/ml) did not block the stimulatory effects of Ca2+ although puromycin and cycloheximide did. The stimulatory effects of Ca2+ on protein synthesis were not restricted to C-6 in minimal medium. Protein synthesis was reduced by ethylene glycol bis(B-aminoethyl ether)-N,N,N',N'-tetraacetic acid 40 to 75% in C-6 glioma, GH3 pituitary tumor, PC-12 adrenal tumor, N2A neuroblastoma, and HeLa cells incubated under simulated growth conditions with various enriched media and sera. Ca2+-depleted S49 lymphoma, CHO ovarian tumor, and normal, dispersed chicken embryo cells in enriched medium responded to Ca2+ restoration with increased rates of protein synthesis as did collagenase-dispersed normal rat liver cells in minimal medium. Protein synthesis in rabbit reticulocyte lysates was also inhibited by Ca2+-selective chelators or by Ca2+ removal by parvalbumin affinity chromatography and the inhibition was reversed by Ca2+. These findings are consistent with the existence of a Ca2+ requirement in the translational phase of protein synthesis in eukaryotic cells.
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PMID:Identification of a Ca2+ requirement for protein synthesis in eukaryotic cells. 631 27

The matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases that are able to degrade the extracellular matrix and allow angiogenesis and tumor invasion. The vast majority of pituitary tumors are benign and do not metastasize to distant sites, although they may invade locally. The aim of this study was to determine whether expression of the collagenase MMP-9 may play a role in allowing angiogenesis and invasion by different pituitary tumor types. Tumor expression of MMP-9 was investigated using a monoclonal antibody on a series of well-characterized paraffin-embedded sections of pituitary tumors. Invasive macroprolactinomas (n = 11) were significantly more likely to express MMP-9 than noninvasive macroprolactinomas (n = 8) (P = 0.003). Invasive macroprolactinomas showed higher-density MMP-9 staining than noninvasive tumors (P < 0.05). MMP-9 expression did not differ between noninvasive tumors and normal pituitary gland, or between different sized prolactinomas. MMP-9 expression was related to aggressive tumor behavior. It was higher in invasive macroprolactinomas (P = 0.003) when compared with noninvasive macroprolactinomas or the normal anterior pituitary gland. In addition, although there was no difference in whether MMP-9 was present or not when nonfunctioning adenomas that recurred were compared with those that did not, samples of recurrent tumor at the second presentation were more likely to express MMP-9 (P = 0.01). Pituitary carcinomas were significantly more likely to be MMP-9 positive compared with normal anterior pituitary gland (P = 0.05), but there was no difference from invasive adenomas. Angiogenesis assessed by vascular density was related to MMP-9 expression (P < 0.05). In summary, we have shown the presence of MMP-9 expression in some invasive and recurrent pituitary adenomas, and in the majority of pituitary carcinoma. The mechanisms whereby MMP-9 expression influences tumor recurrence and invasiveness, and its association with angiogenesis, remains to be elucidated. However, these observations suggest that a future potential therapeutic strategy for some pituitary tumors may be administration of a synthetic MMP-9 inhibitor.
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PMID:Role of matrix metalloproteinase 9 in pituitary tumor behavior. 1094 6

Melatonin exerts a marked antiproliferative action in numerous experimentally-induced tumors in vivo as well as in both animal and human cell lines in vitro. However, the mechanisms of oncostatic action of melatonin is not clear, and the involvement of both membrane and nuclear receptors are suggested. Therefore, the aim of this study was to investigate effects of melatonin, and both agonist (CGP 52608), and antagonist (CGP 55644) of RZR/ROR nuclear receptors on the growth of diethylstilbestrol-induced rat prolactin-secreting pituitary tumor cells in vitro. Pituitary tumors were induced by subcutaneous implantation of a single silastic capsule containing 10 mg of diethylstilbestrol in 4-wk-old male Fischer 344 rats. Four months after the implantation of capsules the animals were killed by decapitation, pituitary tumors were aseptically removed, mechanically dispersed, and enzymatically digested with 0.2% collagenase and 0.2% hyaluronidase. The cells (6 x 105 cells/well) were incubated for 24 hr in the presence of melatonin, CGP 52608, CGP 55644 and CGP 55644 plus melatonin (at the concentrations of 107 and 10-9 m) at 37 degrees C in the humidified atmosphere of 95% air and 5% CO2. The group with the addition of solvent only served as control. The growth of cell was measured using the EZ4U system. Statistical analysis was performed using ANOVA followed by LSD test. Both melatonin and CGP 52608 significantly suppressed growth of tumor cells in vitro in both used concentrations. CGP 55644 stimulated growth of tumor cells and blocked the inhibitory effects of melatonin in vitro. Results of the present study as well as other experimental evidence strongly support the hypothesis that both membrane and nuclear receptors are involved in the oncostatic action of melatonin, and indicate that nuclear signalling plays an important role in this process.
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PMID:Melatonin inhibits growth of diethylstilbestrol-induced prolactin-secreting pituitary tumor in vitro: possible involvement of nuclear RZR/ROR receptors. 1266 53

The clinical features of 426 pituitary adenomas were retrospectively analyzed, focusing on the factors that affect the development of pituitary apoplexy. Immunohistochemical analysis was used to define the different hormone types of the tumors and the expression of various immunologic targets, including the pituitary tumor transforming gene, basic fibroblast growth factor-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and proliferating cell nuclear antigen. Of the 426 patients, 83 presented with pituitary apoplexy (19.48%). Among them, 43 patients (43/83, 51.82%) developed apoplexy in the absence of any obvious precipitating factor. Clinical manifestations included headaches (80/83, 96.38%), vision loss (69/83, 83.13%), pituitary function change (51/83, 61.45%), visual field defects (41/83, 49.39%), and nausea and vomiting (34/83, 40.96%). Male patients and patients with functional adenoma had a higher probability of developing apoplexy. Complicated immunological expression patterns were found in adenomas associated with pituitary apoplexy, with adenomas of different hormone types identified.
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PMID:Clinical features and immunohistochemical changes of pituitary apoplexy. 1904 83