Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. A non-pepsin proteinase, proteinase 2, was successfully isolated free from pepsinogen (by repetitive chromatography on DEAE- and CM-celluloses) from the gastric mucosa of a patient with a duodenal ulcer and the uninvaded mucosa of a patient with a gastric adenocarcinoma. 2. Proteinases 1a and 1b, found in gastric adenocarcinoma, were not found in the gastic mucosa of these patients. 3. Proteinase 2 was shown to have an asymmetrical broad pH-activity curve with a maximum over the pH range 3.0-3.7. 4. Proteolytic activity of proteinase 2 was inhibited by pepstatin; the concentration of pepstatin giving 50% inhibition is of the order of 3nm. 5. Inhibition of proteolytic activity by carbenoxolone and related triterpenoids indicated that at pH 4.0 proteinase 2 possesses structural characteristics relating it to the pepsins and at pH 7.4 to the pepsinogens. 6. The sites of cleavage of the B-chain of oxidized insulin for proteinase 2 at pH 1.7 and pH 3.5 were shown to be similar to those previously established for human pepsin 3 and for the cathepsin E of rabbit bone marrow. 7. The non-pepsin proteinase 2 (cathepsin) of human gastric mucosa has properties more similar to cathepsin E than to the cathepsins D.
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PMID:The isolation and properties of a non-pepsin proteinase from human gastric mucosa. 2 49

We have demonstrated the formation of hybrid insulin/insulin-like growth factor-I(IGF-I) receptors in transfected rodent fibroblasts, which overexpress human receptors, by examining reactivity with species- and receptor-specific monoclonal antibodies. In NIH 3T3 and Rat 1 fibroblasts, endogenous IGF-I receptors were unreactive with anti-(human insulin receptor)monoclonal antibodies (47-9, 25-49, 83-14, 83-7, 18-44). However, in transfected cells expressing high levels of insulin receptors, 60-80% of high-affinity IGF-I receptors reacted with these antibodies, as assessed either by inhibition of ligand binding in intact cells or by precipitation of solubilized receptors. Conversely, endogenous insulin receptors in NIH 3T3 cells were unreactive with anti-(IGF-I receptor) antibodies alpha IR-3 and 16-13. However, approx. 50% of high-affinity insulin receptors reacted with these antibodies in cells expressing high levels of human IGF-I receptors. The hybrid receptors in transfected cells bound insulin or IGF-I with high affinity. However, responses to these ligands were asymmetrical, in that binding of IGF-I inhibited subsequent binding of insulin, but prior binding of insulin did not affect the affinity for IGF-I. The existence of hybrid receptors in normal tissues could have important implications for metabolic regulation by insulin and IGF-I.
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PMID:Receptors for insulin and insulin-like growth factor-I can form hybrid dimers. Characterisation of hybrid receptors in transfected cells. 169 59

These studies were undertaken to assess the subcellular distribution and some biochemical properties of the hepatic cAMP phosphodiesterase(s) whose activity is modulated by the thyroid status in the rat. Thyroidectomy led to a 2-fold increase in low Michaelis-Menten constant (Km) cAMP phosphodiesterase activity in Golgi-endosomal fractions, but little affected this activity in crude particulate fractions. On analytical sucrose density gradients, an increase in cAMP phosphodiesterase activity in particulate elements which equilibrated at densities 1.17-1.22 was also observed. Acute insulin treatment did not further increase cAMP phosphodiesterase activity in Golgi-endosomal fractions of thyroidectomized rats. Up to 75% of the cAMP phosphodiesterase activity associated with Golgi-endosomal fraction of euthyroid and hypothyroid rats was inhibited by cGMP (IC50, 10 microM and 1 microM, respectively). Activity was also potently inhibited by griseolic acid, cilostamide, and cilostazole (IC50, less than 1 microM) but was much less sensitive to R0-20-1724 (IC50, 1 mM). Treatment of Golgi-endosomal fractions by a hypotonic extract of rat liver lysosomes led to the solubilization of 50% of low Km cAMP phosphodiesterase activity. On sucrose density gradients, the solubilized activity migrated as a slightly asymmetrical peak with a sedimentation coefficient of 6 S in euthyroid rats and 6.9 S in hypothyroid rats. On nondenaturing polyacrylamide gel electrophoresis, the activity migrated as two majors peaks with Rf values of 0.23 and 0.50; only the activity associated with the fast-moving peak was increased by thyroidectomy. On diethylaminoethyl-Sephacel chromatography, four peaks of cAMP phosphodiesterase activity, two of which were cGMP-inhibitable, were resolved. Thyroidectomy increased the activity associated with one of the cGMP-inhibitable peaks (eluted at 0.7-0.9 M sodium acetate) and led to the appearance of a new peak of activity (eluted at 0.4 M), which was not sensitive to cGMP. These results show that the low Km phosphodiesterase activity associated with liver Golgi-endosomal fractions, previously shown to be increased in hyperinsulinemic rats, is also increased in hypothyroid animals. They also suggest that, based on pharmacological and physical criteria, the enzyme species affected by the thyroid status belongs to the cGMP-and cilostamide-inhibited subclass of low Km cAMP phosphodiesterases.
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PMID:Characterization of a liver low Michaelis-Menten constant 3',5'-cyclic adenosine monophosphate phosphodiesterase activity sensitive to thyroid status. 185 Mar 51

Transient hypertrophic cardiomyopathy has been described in human infants of diabetic mothers. The purpose of this study was twofold: first, to document the features of cardiac hypertrophy in newborns of female rats with streptozotocin-induced diabetes and second, to investigate the natural history of this cardiomyopathy. Marked asymmetrical septal hypertrophy with hypertrophy of myocytes was observed in newborns of diabetic female rats, whether or not the mothers received daily administration of NPH insulin. The abnormal cardiac morphology was no longer apparent 4 weeks after birth. Thus, in this model, the asymmetrical septal hypertrophy was secondary and was not a manifestation of genetically transmitted hypertrophic cardiomyopathy.
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PMID:The cardiomyopathy in infants of streptozotocin-induced diabetic female rats. 207 51

We describe the distribution of type II insulin-like growth factor receptors among canalicular (cLPM) and basolateral (bLPM) subfractions of rat liver plasma membranes (LPM). BLPM bound 3 times more 125I-IGF II than cLPM. The number of receptors was (1.3 +/- 0.15) X 10(-12) mol/mg in bLPM, and (0.4 +/- 0.17) X 10(-12) mol/mg in cLPM. Insulin-like growth factor II (IGF II) was 10 times more potent than insulin-like growth factor I (IGF I) in displacing 125I-IGF II from both basolateral and canalicular binding sites. Insulin did not interfere with binding of 125I-IGF II in either LPM preparations. Our findings point to an asymmetrical hepatocellular distribution of type II IGF receptors, thus extending the concept of surface polarization of hepatocytes to growth promoting hormone receptors.
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PMID:Polar surface distribution of type II insulin-like growth factor receptor in rat hepatocytes. 217 7

A 38-year-old female was admitted to our hospital because of dyspnea. The diagnosis of total lipodystrophy was made by following findings: (1) gaunt appearance; (2) insulin-resistant diabetes mellitus; (3) hyperlipidemia; (4) fatty liver. Chest X-ray demonstrated cardiomegaly, pulmonary edema and pleural effusion. Echocardiogram was characterized by left ventricular hypertrophy with asymmetrical septal hypertrophy and left ventricular dysfunction. Renal biopsy revealed focal glomerulosclerosis. We reported a patient with total lipodystrophy combined with heart failure and renal failure, which have been rarely associated with the disease.
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PMID:Total lipodystrophy with heart failure and renal failure: report of a case. 253 Mar 77

To characterize the distribution of receptors for insulin-like growth factors I and II (IGF I and II) in the plasma membrane of the renal proximal tubular cell, we measured binding of 125I-labeled IGF I and 125I-labeled IGF II to proximal tubular basolateral and brush-border membranes and characterized IGF I-stimulated phosphorylation of detergent-solubilized membranes. 125I-IGF I bound primarily to a 135,000 relative molecular weight (Mr) protein and IGF II to a 260,000 Mr protein in isolated membranes. Binding of 125I-IGF I was severalfold greater in basolateral than in brush-border membranes. IGF I-stimulated phosphorylation of the 92,000 Mr beta-subunit of its receptor could be demonstrated only in basolateral membranes. These findings are consistent with an asymmetrical distribution of receptors for IGF I in the plasma membrane of the renal proximal tubular cell, localization being primarily on the basolateral side. In contrast, binding of 125I-IGF II to isolated basolateral and brush-border membranes was equivalent, suggesting that receptors for this peptide are distributed more symmetrically in the plasma membrane. Our findings suggest that the actions of IGF I in proximal tubule are mediated via interaction of circulating peptide with specific receptors in the basolateral membrane. However, our findings establish the potential for actions of IGF II to be exerted in proximal tubule via interaction with both basolateral and/or brush-border membrane receptors.
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PMID:Distribution of IGF receptors in the plasma membrane of proximal tubular cells. 296 Dec 73

A 16-year-old boy with insulin-dependent diabetes mellitus since age five years was admitted with severe ketoacidosis, and suffered a cardiorespiratory arrest from which he made a full recovery. He subsequently developed the typical clinical picture of diabetic amyotrophy with painful asymmetrical weakness and wasting of proximal lower limb muscles. Cerebrospinal fluid protein was elevated, and electromyography showed typical changes. Diabetic amyotrophy has not previously been reported in this age group.
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PMID:Adolescent diabetic amyotrophy. 320 32

Hypophysectomy decreased the basal rate of glucose metabolism in segments of epididymal fat studied in vitro and lowered their maximum capacity to use glucose. However, hypophysectomy changed neither the sensitivity to insulin nor the magnitude of the response when the results were expressed relative to the basal rate of glucose metabolism. Adipocytes isolated from both hypophysectomized and normal rats exhibited a higher basal rate of glucose metabolism than cells remaining in situ in the contralateral tissues, but this consequence of cell isolation was more pronounced for adipocytes of hypophysectomized than normal rats. Glucose metabolism could not be further increased by exposure of the adipocytes of hypophysectomized rats to insulin, whereas insulin produced a 3-to 5-fold stimulation of glucose oxidation in normal adipocytes. The effects of insulin and hypophysectomy on the transport of the nonmetabolizable sugar L-[1-14C]arabinose in tissue segments and isolated adipocytes were also studied. Uptake of L-arabinose was usually more rapid in segments of epididymal fat of normal rats than in segments of tissue obtained from hypophysectomized rats and was significantly accelerated by insulin in both groups. Uptake of L-arabinose was more rapid than normal in adipocytes isolated from hypophysectomized rats and, like glucose metabolism, could not be accelerated by insulin. The same concentration of insulin markedly promoted arabinose uptake in normal adipocytes. Efflux of L-arabinose from segments of tissue from hypophysectomized rats was twice as rapid as that from normal tissue and, in contrast with the rate of efflux from normal tissues, was not accelerated by insulin. The data suggest that in the absence of pituitary secretion, sugar transport in the adipocyte membrane may be asymmetrical. The data also support the view that hypophysectomy renders adipocytes more susceptible than normal to the cell isolation procedure which maximally accelerates glucose utilization and inward transport of arabinose in these cells.
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PMID:Effects of hypophysectomy and cell isolation on the transport of L-arabinose by adipocytes. 388 May 39

The internal pH (pHi) of chick muscle cells is determined by the transmembrane Na+ gradient. Li+, but not K+, Rb+ or Cs+, can substitute for Na+ for regulating the internal pH of chick muscle cells. Pharmacological evidence using amiloride and amiloride analogs has shown that the Na+/H+ exchange system is the membrane mechanism that couples the pHi to the transmembrane Na+ gradient. The pHi dependence of the amiloride-sensitive Na+/H+ exchange mechanism was defined. Internal H+ interacts cooperatively with the Na+/H+ exchange system, in contrast with external H+, thus indicating an asymmetrical behaviour of this exchanger. The half-maximum effect for the activation by the internal H+ of the Na+ transporting activity of the amiloride-sensitive Na+/H+ exchange was observed at pH 7.4. The Hill coefficient of the H+ concentration dependence is higher than 3. Insulin was shown to have no effect on the pHi of chick muscle cells.
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PMID:The Na+-dependent regulation of the internal pH in chick skeletal muscle cells. The role of the Na+/H+ exchange system and its dependence on internal pH. 609 Jan 29


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