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)

The effects of nanosized particles (4-6 nm) of synthetic diamonds on mouse macrophage expression and secretion of lysosomal cathepsins (B and D) and MMP-1 and MMP-9 were studied in vitro. Culturing of peritoneal macrophages in medium with diamond nanoparticles led to an increase in the counts of macrophages expressing the above enzymes and to stimulation of their secretion. However, the manifestations of these effects varied significantly for various enzymes. The data indicate modulation of macrophage functions by nanodiamonds. These results help better understand the possible role of the "corpuscular" xenobiotic factors in the pathogenesis of diseases associated with macrophage capturing of these factors irrespective of their chemical "activity".
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PMID:Modifying Effects of Nanosized Diamonds on Hydrolytic Potential of Macrophages In Vitro. 2621 15

The liver plays a key role in maintaining physiological homeostasis and hepatocytes are largely responsible for this. The use of isolated primary hepatocytes has become an essential tool for the study of nutrient physiology, xenobiotic metabolism and several liver pathologies. Since hepatocytes are removed from their normal environment, the isolation procedure and in vitro culture of primary hepatocytes is partially known to induce undesired metabolic changes. We aimed to perform a thorough metabolic profiling of primary cells before, during and after isolation using state-of-the-art techniques. Extensive metabolite measurements using HPLC were performed in situ in the liver, during hepatocyte isolation using the two-step collagenase perfusion method and during in vitro cell culture for up to 48 hours. Assessment of mitochondrial respiratory capacity and ATP-linked respiration of isolated primary hepatocytes was performed using extracellular flux analysis. Primary hepatocytes displayed a drastic decrease in antioxidative-related metabolites (NADPH, NADP, GSH and GSSG) during the isolation procedure when compared to the in situ liver (P<0.001). Parallel assessment of citric acid cycle activity showed a significant decrease of up to 95% in Acetyl-CoA, Isocitrate/Citrate ratio, Succinate, Fumarate and Malate in comparison to the in situ liver (P<0.001). While the levels of several cellular energetic metabolites such as Adenosine, AMP, ADP and ATP were found to be progressively reduced during the isolation procedure and cell culture (P<0.001), higher ATP/ADP ratio and energy charge level were observed when primary cells were cultured in vitro compared to the in situ liver (P<0.05). In addition, a significant decrease in the respiratory capacity occurred after 24 hours in culture. Interestingly, this was not associated with a significant modification of ATP-linked respiration. In conclusion, major metabolic alterations occur immediately after hepatocytes are removed from the liver. These changes persist or increase during in vitro culture. These observations need to be taken into account when using primary hepatocytes for the study of metabolism or liver physiopathology.
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PMID:From in vivo to in vitro: Major metabolic alterations take place in hepatocytes during and following isolation. 2928 39

Primary human hepatocytes (PHHs) remain the gold standard for in vitro investigations of xenobiotic metabolism and hepatotoxicity. However, scarcity of liver tissue and novel developments in liver surgery has limited the availability and quality of tissue samples. In particular, warm ischemia shifts the intracellular metabolism from aerobic to anaerobic conditions, which increases glycogenolysis, glucose depletion and energy deficiency. Therefore, the aim of the present study was to investigate whether supplementation with glucose and insulin during PHH isolation could reconstitute intracellular glycogen storage and beneficially affect viability and functionality. Furthermore, the study elucidated whether the susceptibility of the tissue's energy status correlates with body mass index (BMI). PHHs from 12 donors were isolated from human liver tissue obtained from partial liver resections using a two-step EDTA/collagenase perfusion technique. For a direct comparison of the influence of glucose/insulin supplementation, we modified the setup, enabling the parallel isolation of two pieces of one tissue sample with varying perfusate. Independent of the BMI of the patient, the glycogen content in liver tissue was notably low in the majority of samples. Furthermore, supplementation with glucose and insulin had no beneficial effect on the glycogen concentration of isolated PHHs. However, an indirect improvement of the availability of energy was shown by increased viability, plating efficiency and partial cellular activity after supplementation. The plating efficiency showed a striking inverse correlation with increasing lipid content of PHHs. However, 60 h of cultivation time revealed no significant impact on the maintenance of albumin and urea synthesis or xenobiotic metabolism after supplementation. In conclusion, surgical procedures and tissue handling may decrease hepatic energy resources and lead to cell stress and death. Consequently, PHHs with low energy resources die during the isolation process without supplementation of glucose/insulin or early cell culture, while their survival rates are improved with glucose/insulin supplementation.
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PMID:Effect of glucose and insulin supplementation on the isolation of primary human hepatocytes. 3183 63

This study examined whether a polyphenol-rich extract from the berries of Aronia melanocarpa L. (AE; chokeberries) may protect from the impact of cadmium (Cd) on the metabolism of collagen in the liver. The study was conducted in an experimental model (rats that were fed a diet containing 1 or 5 mg Cd/kg for 3-24 months) of human exposure to this xenobiotic during a lifetime. The concentration of total collagen and the expression of collagen types I and III at the mRNA and protein levels, as well as the concentrations of matrix metalloproteinases (MMP-1 and MMP-2) and their tissue inhibitors (TIMP-1 and TIMP-2), were assayed. The administration of Cd and/or AE had only a slight and temporary impact on the concentration of total collagen in the liver. The supplementation with AE significantly prevented Cd-mediated changes in the expression of collagen types I and III at the mRNA and protein levels and their ratio (collagen III/collagen I), as well as a rise in the concentrations of MMPs and TIMPs in this organ. The results allow the conclusion that the intake of chokeberry products in the case of Cd intoxication may be effective in prevention from this xenobiotic-induced disturbance in collagen homeostasis in the liver.
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PMID:The Impact of a Polyphenol-Rich Extract from the Berries of Aronia melanocarpa L. on Collagen Metabolism in the Liver: A Study in an In Vivo Model of Human Environmental Exposure to Cadmium. 3292 85


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