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)

Adenosine-degrading enzymes within the liver lobule can modulate both vascular and metabolic effects of circulating adenosine in the liver. Since it has not been fully established whether nonparenchymal cells participate in the elimination of sinusoidal purines, isolated Kupffer cells and endothelial cells were tested for their capacity to degrade extracellular purines. After perfusion and digestion of rat livers by collagenase, the resulting mixed cell population was separated by centrifugal elutriation. The isolated parenchymal and nonparenchymal cells were incubated for up to 2 hr in the presence of [8(-14)C]adenosine, [8(-14)C]guanosine and [8(-14)C]hypoxanthine (50 mumoles per liter). In the deproteinized medium, adenosine, guanosine, inosine, adenine, guanine, xanthine, hypoxanthine, uric acid and allantoin were separated by reversed-phase high-performance liquid chromatography. Radioactive peaks were collected and counted. Nonparenchymal cells catalyzed the degradation of adenosine into inosine and hypoxanthine. However, the formation of xanthine, uric acid or allantoin from adenosine could only be detected in hepatocyte suspensions. Within 15 min, adenosine was completely eliminated from the medium by Kupffer cells, whereas endothelial cells catabolized only less than half of the initial amount of the adenine nucleoside during this time period. Accordingly, incubation of nonparenchymal cells in the presence of hypoxanthine did not result in the formation of further breakdown products of the purine, whereas its catabolites slowly accumulated in the medium of hepatocytes. Guanosine conversion into guanine and xanthine was much slower in endothelial cells as compared to Kupffer cells and hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of nonparenchymal and parenchymal liver cells in the catabolism of extracellular purines. 278 34

Characterization of cells comprising solid tumors will facilitate the rational design of cancer chemotherapy for individual patients. We have prepared cell suspensions from human melanoma, sarcoma, and lung tumors by thinly slicing the tissue with a microtome and scalpels (mechanical release), followed by treatment with a mixture of collagenase II and DNase I (enzymatic release). This method of disaggregation resulted in two cell suspensions for each tumor specimen, and we characterized these suspensions by assessing their dye exclusion capability, ribonucleoside triphosphate pools, cytological profile and clonogenicity in soft agar. The enzymatic method thus yields cells in addition to those obtainable by a mild mechanical procedure, and these cells are similar in cytological profile and clonogenicity in soft agar to those released mechanically. Furthermore, the enzymatically released population is superior to that released mechanically for purposes requiring large numbers of dye-excluding cells having intact ribonucleotide pools.
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PMID:Characterization of cells obtained by mechanical and enzymatic means from human melanoma, sarcoma, and lung tumors. 626 Mar 39

Melatonin receptors were studied in isolated mouse hepatocytes using the 2[(125)I]iodomelatonin binding assay. The binding of 2[(125)I]iodomelatonin to hepatocytes isolated from the mouse using collagenase was stable, saturable, reversible and of high affinity. The equilibrium dissociation constant (K(d)) obtained from saturation studies was 10.0 +/- 0.4 pmol/l (n = 16), which was comparable to the K(d) obtained from kinetics studies (6.9 +/- 1.2 pmol/l, n = 3), and the maximum number of binding sites (B(max)) was 2.9 +/- 0.4 fmol/mg protein (n = 16). The relative order of potency of indoles in competing for 2[(125)I]iodomelatonin binding was 2-iodomelatonin > 2-phenylmelatonin > 6-chloromelatonin > melatonin > 6-hydroxymelatonin > N-acetylserotonin, indicating that the binding was mediated by the ML(1) receptor subtype. The linear Rosenthal plots, the close proximity of the Hill coefficient to unity and the monophasic competition curves suggest that a single class of 2[(125)I]iodomelatonin binding sites is present in the mouse hepatocytes. Guanosine 5'-O-(3-thiotriphosphate) dose-dependently inhibited 2[(125)I]iodomelatonin by lowering the affinity of binding, while no inhibitory effects of adenosine nucleotides were observed, suggesting that the binding sites are G-protein linked. Western immunoblotting was used to identify the melatonin receptor subtype in mouse hepatocytes using anti-Mel(1a) and anti-Mel(1b). Hepatocyte membrane extract reacted with anti-Mel(1b) but not anti-Mel(1a) giving a peptide-blockable band of 36 kD, supporting the hypothesis that the melatonin receptors in mouse hepatocytes are of the Mel(1b) subtype. Melatonin injection and a high plasma glucose level affected 2[(125)I]iodomelatonin binding in the whole mouse liver homogenates. Plasma glucose was elevated by mid-light intraperitoneal injection of melatonin (4 and 40 mg/kg body weight) in a dose-dependent manner with maximum elevation achieved 1 h after injection. 2[(125)I]Iodomelatonin binding at this time showed increased K(d) with no changes in B(max). When the plasma glucose returned to normal within 2 h, the binding remained lowered with increased K(d) but no changes in B(max). Elevation of plasma glucose by 2-deoxyglucose injection (500 mg/kg), on the other hand, decreased the binding by decreasing the B(max) without affecting the K(d). Suppression of plasma glucose by insulin injection (3 IU/kg) did not change the binding. Thus, melatonin may act directly on the liver to elevate the plasma glucose level, and changes in plasma glucose level itself may in turn affect hepatic melatonin binding.
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PMID:Modulation of blood glucose by melatonin: a direct action on melatonin receptors in mouse hepatocytes. 1172 Oct 92

In order to understand a disease process, effective modeling is required that can assist scientists in understanding the pathophysiological processes that take place. Intracerebral hemorrhage (ICH), a devastating disease representing 15% of all stroke cases, is just one example of how scientists have developed models that can effectively mimic human clinical scenarios. Currently there are three models of hematoma injections that are being used to induce an ICH in subjects. They include the microballoon model introduced in 1987 by Dr. David Mendelow, the bacterial collagenase injection model introduced in 1990 by Dr. Gary Rosenberg, and the autologous blood injection model introduced by Dr. Guo-Yuan Yang in 1994. These models have been applied on various animal models beginning in 1963 with canines, followed by rats and rabbits in 1982, pigs in 1996, and mice just recently in 2003. In this review, we will explore in detail the various injection models and animal subjects that have been used to study the ICH process while comparing and analyzing the benefits and disadvantages of each.
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PMID:History of preclinical models of intracerebral hemorrhage. 2172 23