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)

Rat parenchymal hepatocytes isolated with collagenase were cultured as monolayers in Williams medium E supplemented with calf serum. Freshly isolated cells showed very low activities of various liver functions, and they had to be cultured for 6-24 h to allow recovery of these functions. Insulin and dexamethasone greatly increased cell viability in primary. After culture for 24 h, these cells showed various liver functions as seen in vivo and responded well to various added hormones and amino acids. The concentrations of amino acids in the medium regulated synthesis of serum proteins and insulin stimulated lipogenesis, which in turn regulated synthesis of lipoproteins. Insulin also stimulated glycogen synthesis and the stimulation was parallel with the number of insulin receptors. Glucagon stimulated glycogenolysis and its stimulation involved the function of the cytoskeleton. Glucagon and dexamethasone induced various enzymes of amino acid catabolism, such as tryptophan oxygenase, tyrosine aminotransferase and serine dehydratase. These inductions were inhibited by insulin or catecholamine. The effect of catecholamine was due to its alpha-adrenergic action. The beta-action of isoproterenol was low in freshly isolated cells, but increased during culture of the cells. Acquirement of hormonal responses during neonatal development can be studied in this culture system. Mature hepatocytes in culture are usually quiescent, but when insulin and epidermal growth factor were added, DNA synthesis by the cells increased markedly and they showed density-dependent growth. In this culture system, serum could be omitted for 2 days when the dishes were coated with fibronectin without appreciable change of functions, but serum was needed for longer culture of the cells. A factor that increased cell survival was found in serum and in pituitary gland. These results show that hepatocytes in primary culture are a simple and useful system for studies of liver functions in vitro and related works were also reviewed.
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PMID:Use of hepatocytes in primary culture for biochemical studies on liver functions. 612 41

Indoxyl sulfate, a uremic toxin, is accumulated in the serum of chronic kidney disease (CKD) patients. A part of the dietary protein-derived tryptophan is metabolized into indole by tryptophanase in intestinal bacteria. Indole is absorbed into the blood from the intestine, and is metabolized to indoxyl sulfate in the liver. Indoxyl sulfate is normally excreted into urine. In CKD, however, an inadequate renal clearance of indoxyl sulfate leads to its elevated serum levels. The oral adsorbent AST-120 reduces the serum levels of indoxyl sulfate by adsorbing indole in the intestines and stimulating its excretion into feces. I have proposed a protein metabolite theory by which endogenous protein metabolites such as indoxyl sulfate play a significant role in the progression of CKD. A progressive decline in the glomerular filtration rate leads to increased serum levels of endogenous protein metabolites such as indoxyl sulfate, and to the adverse effects of their overload on the remnant nephrons. Indoxyl sulfate stimulates progressive both tubulointerstitial fibrosis and glomerular sclerosis by increasing the expression of transforming growth factor-beta1, a tissue inhibitor of metalloproteinase-1 and proalpha1 (I) collagen, leading to a further loss of nephrons. AST-120 delays the progression of CKD by removing serum indoxyl sulfate. Moreover, indoxyl sulfate induces oxidative stress in tubular cells, mesangial cells, vascular smooth muscle cells, endothelial cells and osteoblasts as well as stimulating aortic calcification in hypertensive rats, it is also involved in the progression of CKD, cardiovascular disease (CVD) and osteodystrophy. Thus, the removal of indoxyl sulfate by AST-120 ameliorates the progression of not only CKD, but also of CVD and osteodystrophy.
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PMID:Uremic toxicity of indoxyl sulfate. 2022 98