Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism by which a clone of HL-60 human promyelocytic leukemia cells designated Tf-Gel-1 expresses reduced levels of the transferrin receptor (TfR) was investigated. Tf-Gel-1 was developed by continuous exposure of HL-60 cells to human iron-saturated transferrin covalently linked to the plant toxin gelonin (Tf-Gel); this variant was five- to sixfold more resistant to Tf-Gel than parental HL-60 cells. The amount of cell surface, as well as of solubilized, TfR and the cycling pools of TfR in Tf-Gel-1 cells, as measured by the binding of [125I]Tf, were all decreased to 20-30% of the levels present in parental cells. The growth of Tf-Gel-1 cells was independent of exogenous Fe3+ and was comparable to that of parental HL-60 cells. Despite the lower levels of TfRs, the Tf-Gel-1 clone retained the capacity to alter receptor expression, depending upon the phase of growth and the intracellular iron concentration, and to down-regulate TfRs in response to inducers of differentiation. Southern hybridization of cellular DNA with TfR cDNA did not reveal differences between parental and Tf-Gel-1 cells in the level and arrangement of the TfR gene. Basal and inducible (repressible) levels of TfR mRNA from Tf-Gel-1 cells, as measured by northern hybridization of cellular RNA with TfR cDNA, were comparable to those of parental cells. Metabolic labeling of cells with [35S]methionine, followed by immunoprecipitation of TfRs, demonstrated that the amount of radioactivity incorporated into TfRs in Tf-Gel-1 cells was reduced to a degree that approximated the decrease in [125I]Tf binding. Cell surface TfRs prepared from exponentially growing parental cells labeled with 125I by the solid-phase lactoperoxidase-glucose oxidase method existed as a doublet, with one form being phosphorylated and the other not phosphorylated. In contrast, Tf-Gel-1 cells not only contained diminished amounts of TfRs but also contained only the phosphorylated form of TfRs in the surface membrane. The decrease in the surface membrane concentration of the TfR in Tf-Gel-1 cells was specific for this glycoprotein, since the levels of other cell surface antigens, such as CD13, CD15 and CD45, were normal in Tf-Gel-1 cells. A reduction in the incorporation of [3H]mannose into the acid-insoluble fraction of cells and an increase in sensitivity to ricin suggested that Tf-Gel-1 cells possessed an aberration in carbohydrate metabolism.
Somat Cell Mol Genet 1992 Jan
PMID:Characterization of the defect in a variant of HL-60 promyelocytic leukemia cells with reduced transferrin receptor expression. 154 69

We have examined pulmonary effects of bradykinin (Bk) in vivo and in vitro in guinea pigs and their potential inhibition by antagonists of Bk B1 and B2 receptors. Bk was a potent bronchoconstrictor in vivo and caused contractions of isolated, epithelium-denuded trachealis. D-Arg[Hyp3,D-Phe7]-Bk (NPC567) and D-arg[Hyp3,Thi5,8,D-Phe7]-Bk (NPC349), B2 receptor antagonists, were weak inhibitors of Bk-induced bronchoconstriction in vivo and were virtually inactive as antagonists of Bk-induced airway smooth muscle contraction. Several other B2 antagonists as well as B1 antagonist, des-Arg9-[Leu8]-Bk, did not inhibit Bk-induced tracheal contraction. The B1 receptor agonist des-Arg9-Bk was without effect on tracheal tone. Tracheal responses to Bk were unaffected by antagonists of muscarinic, histamine, serotonin, and catecholamine receptors. The inability of the antagonists to inhibit Bk is unlikely to be due to their degradation, because NPC567 was only weakly active in the presence of inhibitors of kininase I (EC 3.4.11.2), kininase II (EC 3.4.15.1), and neutral endopeptidase (EC 3.4.24.11). These studies were corroborated by ligand binding experiments in guinea pig and ovine airways. In [3H]Bk binding, the Bk antagonists had no effect in guinea pig trachea, slightly displaced [3H]Bk in ovine trachea, and inhibited approximately 60% of total specific binding in lung. des-Arg9-[Leu8]-Bk and several other agents, including atropine, neurokinin A, substance P, and vasoactive intestinal peptide, had no effect on lung Bk binding. Bk and its analogs were not degraded during the binding assay. These data suggest that pulmonary tissue, particularly in the large airways, contains a novel Bk binding site, a B3 receptor, which may be involved in Bk-induced bronchoconstriction.
Mol Pharmacol 1989 Jul
PMID:Evidence for a pulmonary B3 bradykinin receptor. 254 44

Human alveolar macrophages release in vitro a factor that inhibits both random migration and chemotaxis of human polymorphonuclear neutrophils (PMN). This factor is not cytotoxic and is recovered in culture supernatants of alveolar cells from most nonsmoking normal subjects. The inhibitor can be detected 30 min after cell cultures are established and is still produced after 24 h in culture. Its release was inhibited by cycloheximide. When supernatants are separated by molecular sieving (I-60 Waters HPLC column), most of the inhibitory activity is recovered in the low-molecular-weight fractions of the chromatogram (less than 1,000 D). The inhibitor has a broad spectrum of activity against known chemoattractants in that it reduces significantly the chemotaxis of PMN induced by the formyl peptide FMLP, by the complement fragment C5a, and by leukotriene B4; it also decreases the chemotactic activity associated with a monocyte-derived interleukin 1 preparation and the chemotactic activity derived from alveolar macrophage culture supernatants. The inhibitory factor is partially heat labile, is sensitive to aminopeptidase M, and is nonpolar. Both phorbol myristate acetate (PMA) and FMLP-induced superoxide release by PMN are diminished significantly in the presence of this inhibitory factor (p less than 0.01 for PMA and p less than 0.05 for FMLP). The inhibitor also reduces monocyte chemotaxis but has no effect on monocyte random migration. Finally, studies with [3H]FMLP indicate that this inhibitor does not act at the site of receptor binding on PMN. Thus, human alveolar macrophages can release in vitro both neutrophil chemotactic factors and an apparent neutrophil-inhibiting factor that may modulate positively and negatively the movement and the respiratory burst of neutrophils in the alveolar space.
Am J Respir Cell Mol Biol 1989 Nov
PMID:Human alveolar macrophages release a factor that inhibits phagocyte function. 256 89

In addition to "enkephalinase" (EC 3.4.24.11), two enkephalin-hydrolyzing aminopeptidases recently identified in cerebral membranes--aminopeptidase M (EC 3.4.11.2) and a "puromycin-sensitive" aminopeptidase (also designated "MII" or "aminoenkephalinase")--are potentially involved in endogenous enkephalin inactivation. Their participation in the hydrolysis of the endogenous (Met5)enkephalin released by depolarization of slices from rat globus pallidus was assessed, using three inhibitory agents: bestatin, puromycin, and anti-aminopeptidase M antibodies. The selectivity and potency of these agents were first determined by evaluating their IC50 values for inhibition of [3H](Met5)enkephalin hydrolysis by increasingly complex preparations comprising semipurified aminopeptidases, pallidal membranes, and pallidal slices. Bestatin was a fairly potent inhibitor but lacked selectivity, as there was only a 3-fold difference between its IC50 values for the two aminopeptidases, and it displayed restricted diffusion and degradation in the slice preparation. Puromycin discriminated well between the two aminopeptidases (30-fold difference in IC50 values) and did not show any apparent restricted diffusion in the slice preparation. Antiaminopeptidase M antibodies were highly discriminant (greater than 300-fold difference in IC50 values for the two aminopeptidases) but displayed restricted diffusion. Analysis of the concentration-protection curves of the three agents for recovery of the (Met5)enkephalin released from pallidal slices in the presence of the "enkephalinase" inhibitor, thiorphan, indicated that both aminopeptidases participated in enkephalin degradation but that the role of aminopeptidase M was largely predominant, in contrast with its low relative activity in the preparation.
Mol Pharmacol 1986 Mar
PMID:Characterization of aminopeptidases responsible for inactivating endogenous (Met5)enkephalin in brain slices using peptidase inhibitors and anti-aminopeptidase M antibodies. 286 4

The nephropathy induced by mercuric chloride was assessed in unilaterally nephrectomized (NPX) and sham-operated (SO) rats using histological and urinalysis techniques. This assessment was carried out in order to test whether or not rats are more susceptible to the nephrotoxic effects of mercuric chloride after unilateral nephrectomy and a period allowing for compensatory renal growth. Twelve days after surgery both NPX and SO rats were given a single 1.5, 2.0 or 2.5 mumol/kg dose of mercuric chloride (i.v.). Twenty-four hours after the 1.5 or 2.0 mumol/kg dose of mercuric chloride was administered, cellular and tubular necrosis in the pars recta segments of proximal tubules in the outer medulla was more severe in NPX rats than in SO rats. Moreover, the urinary excretion of a number of cellular enzymes (e.g. lactate dehydrogenase) and plasma solutes (e.g. albumin) was greater in NPX rats than in SO rats. At the 2.5 mumol/kg dose of mercuric chloride, renal tubular damage was quite extensive in both groups of rats; to such an extent that possible differences in renal tubular damage between the NPX and SO rats could not be determined histologically. However, the urinary excretion of alanine aminopeptidase was greater in the NPX rats than in the SO rats. Therefore, based on the aforementioned findings, rats that have undergone and adapted to a reduction in renal mass (i.e. unilateral nephrectomy) appear to be more vulnerable to the nephrotoxic effects of mercuric chloride than rats with two normal kidneys.
Virchows Arch B Cell Pathol Incl Mol Pathol 1987
PMID:Mercuric chloride-induced nephrotoxicity in the rat following unilateral nephrectomy and compensatory renal growth. 289 Dec 17

The pepN gene codes for aminopeptidase N whose expression is regulated at the transcriptional level by anaerobiosis and phosphate starvation. To define and characterize the functional region of the pepN promoter (pepNp), various promoter fragments were fused to the malPQ operon of Escherichia coli and transferred to the chromosome. The expression of the single copy operon fusion was measured by assaying the amylomaltase activity. Sequences upstream from the canonical promoter elements, located 110 to 60 bp preceding the transcription start site, are important for promoter functioning. This region plays a role in the expression of the two divergent promoters pepNp and pncBp. The regulation of pepNp under phosphate starvation was conserved in the various constructs in which pepNp is functional. However, no particular sequence specific for phosphate regulation was detected. In addition, the regulation of pncBp by Pi starvation was demonstrated.
Mol Gen Genet 1987 Dec
PMID:Deletion analysis of the promoter region of the Escherichia coli pepN gene, a gene subject in vivo to multiple global controls. 289 44

The cellular distribution of a highly antigenic fibroblast glycoprotein, identified previously as aminopeptidase M, was studied in vitro by immunofluorescence and immuno-electron microscopy. The antigen was found to be localized at the surface of live and fixed fibroblasts in suspension and in cell layer; clustering or patching on live cells could be observed. Immunofluorescence after permeabilization of the cells with acetone showed distribution of the antigen in cytoplasmic granules. The tissue distribution of this antigen was examined by immunofluorescence on frozen sections of various human organs. In addition to fibroblasts, renal tubules, liver, pancreas and gut were found to react selectively with the antibody preparation. Moreover, a specific localization of the reaction product was observed. In the kidney the epithelium and brush border of the proximal convoluted tubules were stained. In the liver, the bile canaliculi reacted; in the pancreas the acinar cells and in the gut the brush border of the mucosal cells of the villi and crypts were stained. The same cells did not stain with an antiserum prepared in a similar fashion against another fibroblast component, or with preimmune IgG. In most sections of the selectively stained tissues, a predominant localization at the apical pole of the cells was observed. The localization of the antigen in different tissues corresponds with the distribution of aminopeptidase M, thereby confirming its identity and the antigenic cross-reaction between the fibroblast and tissue enzyme.
Virchows Arch B Cell Pathol Incl Mol Pathol 1981
PMID:Localization of a highly antigenic human fibroblast surface glycoprotein (FSG) on fibroblasts and on epithelia involved in secretion or resorption. 611 5

The enzymatic digestion of some radiolytically produced peptidic materials was examined. The substrates were compounds isolated from 0.1 molar solutions of NH4CN (pH 9) and HCN (pH 6), after their exposure to gamma rays from a 60Co source (15-20 Mrad doses). Commercial proteolytic enzymes pronase and aminopeptidase M were used. The examined materials were of composite nature and proteolytic action was systematically observed after their subsequent purification. In some fractions the effect was found to be positive with up to 30% of peptide bonds cleaved with respect to the amino acid content. These findings support our previous conclusions on the free radical induced formation of peptidic backbones without the intervention of amino acids. Some side effects were also noted which might be of interest in observations on enzymatic cleavage of other composite peptidic materials of abiotic origin.
J Mol Evol 1982
PMID:Enzymatic characterization of peptidic materials isolated from aqueous solutions of ammonium cyanide (pH 9) and hydrocyanic acid (pH 6) exposed to ionizing radiation. 612 39

The pepN gene, that encodes aminopeptidase N in Escherichia coli, has been cloned into the multicopy plasmid pBR322. Expression of the cloned pepN gene results in overproduction of the enzyme. The restriction map of the 6.7 Kb insert was established and the gene was further localized by analysis of the in vitro constructed delection plasmid and mutant plasmids generated by Tn5 insertions. Chromosome mobilization experiments, using pep-N-lac fusion strains allowed us to infer a clockwise direction of transcription for the pepN gene.
Mol Gen Genet 1984
PMID:Cloning and orientation of the gene encoding aminopeptidase N in Escherichia coli. 614 45

Several new synthetic substrates fulfilling the specificity requirements of cathepsin D were synthesized. One of these D-Phe-Ser(O-CH2-C6H5)-Phe-Phe-Ala-Ala-pAB(pAB = p-aminobenzoate) proved to be highly sensitive and convenient for measuring activity. Enzyme determination was carried out in a two-step reaction. In the first step the enzyme hydrolyzes the Phe-Phe bond of the substrate at pH 3.4. In the second step aminopeptidase M (EC 3.4.11.2) degrades one of the products Phe-Ala-Ala-pAB at pH 7 to 8 with the release of free pAB, which is then determined by a diazotization procedure. Activity can be measured in as little as 1 to 5 micrograms of macrophage protein. The activity of cathepsin D in rat alveolar macrophages was almost ten times higher than in resident peritoneal macrophages, and more than 25 times higher than in blood monocytes. The data indicate that transformation of blood monocytes into macrophages is associated with a much greater increase of cathepsin D activity in alveolar than peritoneal macrophages.
Mol Cell Biochem 1984 Sep
PMID:A sensitive procedure for determination of cathepsin D: activity in alveolar and peritoneal macrophages. 615 Apr 34


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