Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Cells obtained by continuous perfusion with collagenase maintained their ultrastructure and their capacity for protein synthesis in contrast to mechanically isolated rat liver cells. Albumin and angiotensinogen (renin substrate) are synthesized and secreted and the synthesis of both proteins is stimulated by addition of hydrocortisone. As cell suspensions allow the simultaneous investigation of several samples under well defined conditions they can serve as an excellent model for the study of regulatory mechanisms of serum protein synthesis.
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PMID:[Blood protein synthesis in isolated liver cells]. 19 70

Recent studies have found that angiotensinogen is expressed in white and brown fat pads, and adipocytes have been implicated as a primary source of angiotensinogen in several other tissues. The functional significance of this unexpected expression is unknown. To address this, we studied angiotensinogen messenger RNA (mRNA) expression and angiotensinogen secretion in adipose tissue and isolated adipocytes comparing fasted and refed rodents and those with genetic obesity with normal controls. Control 2-month-old Sprague-Dawley rats, those fasted for 3 days, or those fasted for 2 days and refed for 6 days were killed, and adipocytes were isolated from epididymal fat pads using collagenase digestion. Angiotensinogen mRNA was reduced to 14.6 +/- 2.3% of control levels under fasted conditions and increased to 228 +/- 53% of control levels after refeeding. Angiotensinogen release from adipocytes was reduced to 33% of control levels by fasting and increased to 183% by refeeding. These effects of fasting and refeeding on angiotensinogen regulation were tissue specific since liver angiotensinogen mRNA and serum angiotensinogen concentrations were unaffected. Systolic blood pressure, however, was modulated by fasting and refeeding in a manner parallel to adipocyte angiotensinogen expression. In related experiments, angiotensinogen secretion per epididymal fat pad of the ob/ob mouse model of obesity was increased an average of 3.4-fold compared with control. We conclude angiotensinogen expression in white adipocytes is regulated nutritionally in a tissue-specific manner. We propose that adipocyte angiotensinogen could play a previously unrecognized role in regulating adipose tissue blood supply and thereby fatty acid efflux from fat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tissue-specific nutritional regulation of angiotensinogen in adipose tissue. 155 65

The effect of angiotensin II (ANG II) on the secretion of angiotensinogen was studied in isolated rat hepatocytes, obtained by the collagenase perfusion technique and Percoll-density gradient centrifugation, and in the isolated perfused rat liver. In isolated hepatocytes, steady state concentrations of about 1, 10 or 100 nM of ANG II during 90 min of preincubation resulted in a 5, 27 and 33% increase of angiotensinogen secreted during a subsequent 3 hour incubation period. Secretion rates during the last hour of incubation were increased by about 70% by the two higher ANG II concentrations, as compared to controls. Hydrocortisone also induced an increased secretion of angiotensinogen in hepatocytes. The effect of ANG II was prevented by saralasin, a competitive ANG II-antagonist and by actinomycin D. ANG II had no effect of the rate of albumin secretion and of total protein secretion. In the isolated perfused liver, ANG II induced a similar increase of angiotensinogen secretion, without affecting albumin and total protein secretion rates. These observations are consistent with the view that ANG II is participating in a feed back stimulation system of angiotensinogen synthesis and secretion in vivo.
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PMID:Induction of angiotensinogen synthesis and secretion by angiotensin II. 343 79

Isolated hepatocytes were prepared from rat liver by collagenase perfusion and density gradient centrifugation. The hepatocyte preparation released angiotensinogen at a basal rate of 50-120 pmol/g wet weight per h. Release was linear with time for at least 4 h. Angiotensinogen secretion was reduced in the presence of actinomycin D, and inhibited by cycloheximide, puromycin, colchicine and vinblastine. In the presence of tunicamycin, an inhibitor of N-glycosylation, the secretion of angiotensinogen as well as total protein and albumin secretion were diminished. Hepatocytes from nephrectomized rats exhibit an increased secretion rate of angiotensinogen, whereas total protein secretion was unaltered. Preincubation of hepatocytes with hydrocortisone (0.1 mM) or angiotensin II (10 nM) induced an increase of angiotensinogen release. There was no concomitant increase of total protein or albumin secretion, indicating that these effects are not the expression of a general stimulation of protein synthesis and secretion.
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PMID:Hormonal and pharmacological alteration of angiotensinogen secretion from rat hepatocytes. 395 81

Immortalized rat proximal tubule cell (IRPTC) lines should be useful for investigation of proximal tubule (PT) regulation and function but previously have been unavailable. We now report the establishment and characterization of an immortalized transformed, temperature-sensitive IRPTC cell line containing renin-angiotensin system (RAS) components. Primary PT cells prepared from male Wistar rats (4-5 wk old) after collagenase digestion, sieving, and Percoll gradient were cultured on collagen-coated T-75 flasks in Dulbecco's modified Eagle's medium containing 5% fetal calf serum. Subconfluent PT cells were transfected with the temperature-sensitive SV40 mutant viruses (tsA SV40) by direct exposure. After 7-8 wk, several clones were obtained, from which one has been characterized and designated as line 3-2. This cell line appears stable up to 45 passages. Clonal cells transformed with this virus exhibit a transformed phenotype at a permissive temperature of 34 degrees C and grow in multiple layers. When the cells are subsequently placed at a nonpermissive temperature of 41 degrees C, they return to morphology similar to that of untransformed cells of the same lineage. At either 34 degrees C or 41 degrees C, this cell line expresses a variety of PT markers including alkaline phosphatase, cytokeratin, carbonic anhydrase, and glucose transporter isoform 2 (GLUT2), while not expressing factor VIII. Uniquely, these cells also appear to express PT proteins gp330 and CHIP28, markers which are usually lost in cultured cells. Furthermore, the cell line expresses protein and mRNA components of RAS, including angiotensinogen, angiotensin converting enzyme, and renin. The IRPTC cell line expresses few angiotensin II (ANG II) receptors at 34 degrees C, the permissive temperature. However, at the nonpermissive temperature, 41 degrees C, IRPTC expresses ANG II receptor (dissociation constant of 0.7 nM; maximum binding capacity of 265 fmol/mg protein). ANG II (10(-8) M) induced a transient rise in cytoplasmic Ca2+ concentration, which was nearly abolished with losartan but not PD-123319, suggesting this finding is AT1 receptor mediated. This cell line should provide an excellent model of PT and should make it possible to study the cell and molecular biology of the RAS, as well as other regulatory systems of the PT.
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PMID:Temperature-sensitive SV40 immortalized rat proximal tubule cell line has functional renin-angiotensin system. 790 Aug 43

1. The mechanisms whereby angiotensin converting enzyme inhibitors reverse cardiac remodelling appear to involve angiotensin and/or bradykinin receptors. Previously we reported that cultured rat cardiac fibroblasts express angiotensin II (AII) receptors. In the present study we compared AII receptor binding, gene expression of angiotensinogen and the AII, Subtype 1A (AT1A) receptor, as well as morphological changes induced by selected hormonal treatments in cultured fibroblasts derived from SHRLJ or WKYLJ rats. 2. Fibroblasts were isolated from adult rat left ventricle by either collagenase B or collagenase P digestion. Collagenase B yielded cell preparations from SHRLJ which grew slower than cells from WKYLJ rats and expressed nearly two-fold fewer AII receptors (compared to WKYLJ) while collagenase P yielded SHRLJ cells with similar binding and growth properties to WKYLJ. A good correlation was observed between receptor binding and AII receptor, type 1A (AT1A) mRNA concentrations. In the presence of steroids collagenase B cells showed a higher tendency to transform towards a preadipocyte cell type, estimated by the formation of lipid containing vacuoles/cell, while collagenase P cells, mainly the SHRLJ type, start to differentiate toward a myofibroblast-like cell type in the presence of AII, as calculated by the expression of alpha-smooth muscle actin. 3. From the results obtained in this study it is evident that a subset of fibroblasts can be isolated from the SHRLJ heart using collagenase B or P which differ in growth rates, AII receptor binding, AT1A and angiotensinogen mRNA levels, morphology and steroid responsiveness when compared to fibroblasts isolated from cardiac WKYLJ tissue.
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PMID:Differences in cultured cardiac fibroblast populations isolated from SHR and WKY rats. 907 84

Considerable evidence suggests that the intrarenal renin-angiotensin system plays an important role in diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II (Ang II) receptor blockers (ARBs) can attenuate progressive glomerulosclerosis in disease models and can slow disease progression in humans. Because agents that interfere with Ang II action may decrease glomerular injury without altering glomerular pressures, it has been suggested that Ang II has direct effects on glomerular cells to induce sclerosis independent of its hemodynamic actions. To study nonhemodynamic effects of Ang II on matrix metabolism, many investigators have used cell culture systems. Glucose and Ang II have been shown to produce similar effects on renal cells in culture. For instance, incubation of mesangial cells in high-glucose media or in the presence of Ang II stimulates matrix protein synthesis and inhibits degradative enzyme (e.g., collagenase, plasmin) activity. Glucose and Ang II also can inhibit proximal tubule proteinases. Glucose increases expression of the angiotensinogen gene in proximal tubule cells and Ang II production in primary mesangial cell culture, which indicates that high glucose itself can activate the renin-angiotensin system. The effects of glucose and Ang II on mesangial matrix metabolism may be mediated by transforming growth factor-beta (TGF-beta). Exposure of mesangial cells to glucose or Ang II increases TGF-beta expression and secretion. Their effects on matrix metabolism can be blocked by anti-TGF-beta antibody or ARBs such as losartan, which also prevents the glucose-induced increment in TGF-beta secretion. Taken together, these findings support the hypothesis that the high-glucose milieu of diabetes increases Ang II production by renal, and especially, mesangial cells, which results in stimulation of TGF-beta secretion, leading to increased synthesis and decreased degradation of matrix proteins, thus producing matrix accumulation. This may be an important mechanism linking hyperglycemia and Ang II in the pathogenesis of diabetic nephropathy.
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PMID:Role of angiotensin II in diabetic nephropathy. 1099 97

Obesity and its associated disorders are increasing in companion animals, particularly in dogs. We have investigated whether genes encoding key adipokines, some of which are implicated in the pathologies linked to obesity, are expressed in canine adipose tissues. Using RT-PCR, mRNAs encoding the following adipokines were detected in dog white adipose tissue: adiponectin, leptin, angiotensinogen, plasminogen activator inhibitor-1, IL-6, haptoglobin, metallothionein-1 and 2, and nerve growth factor. The adipokine mRNAs were present in all fat depots examined. Fractionation of adipose tissue by collagenase digestion showed that each gene was expressed in mature adipocytes. The mRNA for TNFalpha was not evident in adipose tissue, but was detected in isolated adipocytes. Fibroblastic preadipocytes from gonadal white fat were differentiated into adipocytes in primary culture and adipokine expression examined before and after differentiation (days 0 and 11, respectively). Each adipokine gene expressed in dog white adipocytes was also expressed in the differentiated cells. These results demonstrate that dog white adipose tissue expresses major adipokine genes, expression being in the adipocytes. Investigation of adipokine production and function will provide insight into the mechanisms involved in obesity-related pathologies in dogs and serve as a model for the related human diseases.
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PMID:Adipokine gene expression in dog adipose tissues and dog white adipocytes differentiated in primary culture. 1613 59

The messenger RNA (mRNA) distribution of 60 proteins was examined in the 3 fractions obtained by collagenase digestion (fat cells and the nonfat cells comprising the tissue remaining after collagenase digestion [matrix] and the stromovascular cells) of omental adipose tissue obtained from morbidly obese women undergoing bariatric surgery. Fat cells were enriched by at least 3-fold as compared with nonfat cells in the mRNAs for retinol binding protein 4, angiotensinogen, adipsin, glutathione peroxidase 3, uncoupling protein 2, peroxisome proliferator-activated receptor gamma, cell death-inducing DFFA-like effector A, fat-specific protein 27, 11beta-hydroxysteroid dehydrogenase 1, glycerol channel aquaporin 7, NADPH:quinone oxidoreductase 1, cyclic adenosine monophosphate phosphodiesterase 3B, glyceraldehyde-3-phosphate dehydrogenase, insulin receptor, and amyloid A1. Fat cells were also enriched by at least 26-fold in the mRNAs for proteins involved in lipolysis such as hormone-sensitive lipase, lipoprotein lipase, adipose tissue triglyceride lipase, and FAT/CD36. The relative distribution of mRNAs in cultured preadipocytes was also compared with that of in vitro differentiated adipocytes derived from human omental adipose tissue. Cultured preadipocytes had far lower levels of the mRNAs for inflammatory proteins than the nonfat cells of omental adipose tissue. The nonfat cells were enriched by at least 5-fold in the mRNAs for proteins involved in the inflammatory response such as tumor necrosis factor alpha, interleukin lbeta, cyclooxygenase 2, interleukin 24, interleukin 6, and monocyte chemoattractant protein 1 plus the mRNAs for osteopontin, vaspin, endothelin, angiotensin II receptor 1, butyrylcholinesterase, lipocalin 2, and plasminogen activator inhibitor 1. The cells in the adipose tissue matrix were enriched at least 3-fold as compared with the isolated stromovascular cells in the mRNAs for proteins related to the inflammatory response, as well as osteopontin and endothelial nitric oxide synthase. We conclude that the mRNAs for inflammatory proteins are primarily present in the nonfat cells of human omental adipose tissue.
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PMID:Comparison of messenger RNA distribution for 60 proteins in fat cells vs the nonfat cells of human omental adipose tissue. 1855 44

Liver fibrosis is a common consequence of chronic liver diseases resulting from multiple etiologies. Furthermore, prolonged unresolved liver fibrosis may gradually progress to cirrhosis, and eventually evolve into hepatocellular carcinoma (HCC). Corydalis saxicola Bunting (CS), a type of traditional Chinese folk medicine, has been reported to have hepatoprotective effects on the liver. However, the exact mechanism of how it cures liver fibrosis requires further elucidation. In this work, an integrated approach combining proton nuclear magnetic resonance (¹H-NMR)-based metabonomics and network pharmacology was adopted to elucidate the anti-fibrosis mechanism of CS. Metabonomic study of serum biochemical changes by carbon tetrachloride (CCl₄)-induced liver fibrosis in rats after CS treatment were performed using ¹H-NMR analysis. Metabolic profiling by means of partial least squares-discriminate analysis (PLS-DA) indicated that the metabolic perturbation caused by CCl₄ was reduced after CS treatment. As a result, lipids, leucine, alanine, acetate, O-acetyl-glycoprotein and creatine were significantly restored after CS treatment, which regulated valine, leucine and isoleucine metabolism; arginine and proline metabolism; lipid metabolism and pyruvate metabolism. Additionally, 157 potential targets of CS and 265 targets of liver fibrosis were identified by means of network pharmacology. Subsequently, 5 target proteins, which are the intersection of potential CS targets and liver fibrosis targets, indicated that CS has potential anti-fibrosis effects through regulating alanine aminotransferase (ALT) activity, the farnesoid X receptor (FXR), cyclooxygenase-2 (COX-2), matrix metalloproteinase-1 (MMP-1) and angiotensinogen. Chelerythrine and sanguinarine were the potential active compounds in CS for treating liver fibrosis through regulating ALT activity. This study is the first report to study the anti-fibrosis effects of CS on the basis of combining a metabonomics and network pharmacology approaches, and it may be a potentially powerful tool to study the efficacy and mechanisms of traditional Chinese folk medicines.
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PMID:Investigation of the hepatoprotective effect of Corydalis saxicola Bunting on carbon tetrachloride-induced liver fibrosis in rats by ¹H-NMR-based metabonomics and network pharmacology approaches. 2999 Aug 93


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