Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biological characteristics of a kidney growth factor (KGF) from uninephrectomized rat plasma have been studied. A crude preparation of this factor [Nephrol. Dial. Transplant. 4: 334-338, 1989] was further purified by hydrophobic interaction HPLC and gel filtration. KGF was found to be a heat- and trypsin-resistant protein. This factor stimulated dose-dependently DNA synthesis by the mouse kidney in vivo, and by either rat renal tubules or serum-deprived LLC-PK1 cells, in vitro. KGF also increased protein synthesis in these cells, in a dose-dependent manner. Moreover, KGF stimulated sodium uptake by these cells, associated with the maximal increase of protein synthesis. Our findings indicate that KGF is a potent renotropic protein which can play a key role in the renal compensatory growth after uninephrectomy.
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PMID:Biological properties of a renotropic protein present in plasma of uninephrectomized rats. 172 Feb 53

Renal growth factor activity was extracted from plasma of adult uninephrectomised rats and partially purified by gel filtration and anion-exchanger FPLC. It induced a maximal stimulation of mouse DNA synthesis in vivo at 1.75 micrograms/mouse. In addition, renal growth factor was found to maximally stimulate DNA synthesis in LLC-PK1 cells at 150 ng/ml. This maximal response was then found to decrease with higher doses of renal growth factor, in vivo and in vitro. The apparent molecular weight of renal growth factor was estimated to be 17K-22 K by gel filtration. It was found to be resistant to heat and to trypsin, but labile to reduction with dithiothreitol.
Nephrol Dial Transplant 1989
PMID:Partial purification and characterisation of a renal growth factor from plasma of uninephrectomised rats. 250 82

The sera of 21 patients positive for antibodies against GBM in indirect immunofluorescence tests were examined by immunoblotting. We demonstrated antibodies against 50, 48, 43 and 29 kD molecular weight peptides in 20 of 21 sera using collagenase-digested GBM, in 19 of 21 using trypsin-digested GBM, and in 10 of 21 using elastase-digested GBM. Although the spectrum of molecular weights of the antigenic proteins was similar in all three digests, they differed with respect to preservation of antigenicity upon reduction with mercaptoethanol. Many of the sera of patients and controls reacted with proteins unrelated to GBM, e.g. albumin and prealbumin. Furthermore, some control sera reacted with one single peptide of the above-mentioned specific GBM peptides. Our results suggest that the highly purified 29 kD peptide of the collagenase digest or the 50 kD peptide of the trypsin digest provide the best antigens to develop a screening test for antibodies against GBM. However, serum antibodies against these antigens will not be absolutely specific for anti-GBM antibody-mediated nephritis, as shown by the immunoblot experiments.
Nephrol Dial Transplant 1986
PMID:Characterisation and specificity of glomerular basement membrane antigens identified by sera of patients with anti-GBM nephritis. 311 Jun 69

Whilst chronic renal failure (CRF) patients are known to have an impaired immune response the explanation is unclear. We investigated the immunosuppressive effect of plasma from CRF patients on an in vitro assay of normal lymphocyte function. One hundred and sixty regular dialysis patients had significantly greater plasma suppressive activity (PSA) than that of normal healthy subjects. PSA decreased after haemodialysis but increased after blood transfusion. Renal allograft recipients with low PSA were more likely to have accelerated rejection. Assay of the functional capacity of plasma for inhibiting protease (e.g. plasmin, thrombin, trypsin) suggest that high PSA is associated with the excess formation of protease-inhibitor complexes and liberation of immunoregulatory peptide (less than 10,000 daltons).
Proc Eur Dial Transplant Assoc 1983
PMID:A new mechanism of humoral immunodepression in chronic renal failure and its importance to dialysis and transplantation. 636 42

Mouse pancreatic proteases were analyzed by one- and two-dimensional electrophoresis. Active proteases that existed in the luminal fluid were separated into at least eight bands in 8% polyacrylamide gel. Pancreatic proteases activated by intestinal extract were separated into at least seven bands. The mobilities of these bands were exactly the same as those of proteases in the luminal fluid except for those of the most cathodal band. Two kinds of trypsin (Try-I group and Try-II) and one kind of chymotrypsin (Chy-I) were determined by specific and nonspecific protease staining. Try-I group and Try-II were derived from different trypsinogens (Try G-I group and Try G-II), whereas Chy-I was derived from a single chymotrypsinogen (Chy G). Although Try G-II was activated by both intestinal extract and by bovine trypsin, Try G-I group activated only by intestinal extract. Intestinal-activating factors were analyzed by two-dimensional electrophoresis. Mouse enterokinase (enteropeptidase EC 3.4.4.8), which can activate bovine trypsinogen, had a slow mobility. In the intestine of the mouse there are several activating factors in addition to enterokinase. Although it is unclear what intestinal-activating factors can activate Chy G, there is a factor that can convert chymotrypsinogen into chymotrypsin directly. These data suggest that intestinal-activating factors play an important role in the activating mechanisms of mouse pancreatic zymogens.
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PMID:Electrophoretic analysis of pancreatic proteases and zymogen-activating factors in the mouse. 637 96

Recently it has been shown that protease therapy ameliorates certain immune-mediated diseases. Thus we studied the effect of administration of a protease mixture on aortic transplant arteriosclerosis in rats. Segments of abdominal aorta from SHR strain were transplanted orthotopically into WKY recipients. Two groups of allografted rats were used. One group (n = 8) was treated with daily intraperitoneal injections of 12 mg of a protease formulation containing trypsin, bromelain and rutosid, and another group (n = 8) with placebo. Eight WKY rats were transplanted with syngenic aortas and treated with placebo. After 8 weeks, structural changes of the grafted segment were evaluated by morphometric analysis of formalin-fixed sections with specific stains. In untreated allografts there was a marked intimal thickening, medial necrosis with disruption of elastic fibres, and inflammatory infiltrates in the adventitia. Administration of proteases inhibited formation of neointima by 59.0% when cross-sectional areas were compared (80+/-11 versus 195+/-11 microm2, P<0.01; protease-versus placebo-treated allograft recipients respectively) and decreased medial injury as estimated by the integrity of elastic fibres and smooth-muscle cell density. Thus, in an experimental model of rat aortic allograft, protease administration ameliorates rejection-induced arterial wall remodelling.
Nephrol Dial Transplant 1996 Jun
PMID:Beneficial effect of proteases on allograft arteriosclerosis in a rat aortic model. 867 57

Sphingolipids are emerging as important regulators of mammalian cell biology. In this study, the contents of six separate preparations of human omental mesothelial cells in vitro were examined for free sphingosine and sphinganine, and for the total levels of these sphingoid bases in ceramide-containing sphingolipids. Two high-performance liquid chromatography (HPLC) methods for determination of sphingoid base levels in cultured cells were compared. The rapid-HPLC method was found to yield the highest recovery of internal standard. Mesothelial cells initially isolated by collagenase digestion of the omentum were found to have higher free- and total-sphingoid base levels than cells isolated by trypsin-EDTA digestion. Use of sphingoid base levels to gain insights into the status of cellular nutrition, inflammation, programmed cell death, exposure to microbial toxins, cytokines, and growth factors within the peritoneum will require a systematic description of sphingolipids in normal, diseased, and dialyzed mesothelium.
Adv Perit Dial 1998
PMID:Sphingosine and sphinganine levels in human mesothelial cells in vitro as a potential index of signal transduction pathways impacted by microbes and osmolality. 1064 16

To analyze the regulation of water channels in the peritoneum, we tried to establish a primary mesothelial cell culture system. Male Sprague-Dawley rats weighing about 250 g were anesthetized, and 10 mL of phosphate-buffered saline (PBS) containing 0.25% trypsin and 1 mmol/L ethylenediamine tetraacetic acid (EDTA) was infused into the peritoneal cavity for 15 minutes. Sediments from the recovered fluid were cultured in medium M199 supplemented with 10% fetal bovine serum (FBS). The culture was succeeded 4-6 times before experiments commenced. After exposure to the test medium, RNA was extracted and subjected to reverse transcriptase polymerase chain reaction (RT-PCR) for 10-19 cycles, then was measured by Southern blot analysis with a digoxin-labeled probe. Cultured cells were positively stained with mouse monoclonal anti-cytokeratin antibody, confirming their characteristics as mesothelial cells. Aquaporin-1 (AQP-1) message in the cultured cells increased with increases in glucose and mannitol concentrations when beta-actin message was used as an internal control. Tranexamic acid effected no change in AQP-1 message in the cultured mesothelial cells. This system offers potential as a simple approach to test the effects of osmolytes, cytokines, and vasoactive hormones on aquaporin expression and water transport in the peritoneum.
Adv Perit Dial 1999
PMID:Water channel AQP-1 in the primary cell culture of rat peritoneum. 1068 62

Proteasome (PS) is a sophisticated protein degradation machinery comprising a 20S proteolytic core particle provided with caspase-like, trypsin-like and chymotrypsin-like activities on ubiquitinilated proteins. The products of this selective, complex, controlled and strictly coordinated system play a crucial role in cell cycle progression and apoptosis; activation of transcription factors, cytokines and chemokines; degradation and generation of MHC class I-presented peptides. PS has recently emerged as a promising drug target in cancer therapy, and bortezomib has been approved for refractory multiple myeloma. PS proteolysis is crucial for the degradation of the inhibitory protein IkB of nuclear factor kB (NF-kB), and hence, an interesting field of research has been developed on possible benefits of drugs with anti-PS activity in disease conditions with hyper-expression of NF-kB. PS inhibitors are being adopted in pilot studies in antibody-mediated renal rejection and in AL amyloidosis, with increasing scientific interest in possible applications in lupus, IgA nephropathy, idiopathic nephrotic syndrome and renal fibrosis. The most often used PS inhibitor, bortezomib, has a severe peripheral neurotoxicity, and the search for effective and less toxic PS-targeted drugs is a challenging area also in nephrology.
Nephrol Dial Transplant 2014 Feb
PMID:Proteasome inhibitors in progressive renal diseases. 2449 67