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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Purified mouse nerve growth factor (NGF)radiolabeled with 125I was tested for its ability to bind to a variety of different cultured cells. NGF binds readily to human and hamster melanoma cells but does not bind to many other cell lines. The three cell lines with the highest number of NGF receptors were derived from metastatic melanomas. One of these lines, A875, was studied in detail and was shown to have approximately 7x10(5) NGF receptors per cell with an association constant of 1.0x10(9) liters/mole. The use of these cells in competition binding assays permits the detection of 0.25 ng of NGF in various biologic fluids. NGF can be shown to increase the survival, but not the division, of melanoma cells maintained in medium depleted of serum growth factors. This effect of NGF as a specific "survival factor" appears analogous to its effect on cultured sympathetic ganglion cells and on other cells derived from the neural crest.
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PMID:Nerve growth factor receptors on human melanoma cells in culture. 26 22

RNA synthesis in melanocytes and nevus cells, and the proliferation of those cells in the presence of nerve growth factor (NGF) and 12-0-tetradecanoyl-phorbol-13-acetate (TPA), were found to correlate with the amount of NGF bound to the chromatin versus the total internalized NGF (n/c NGF = nuclear/cellular ration). In nevus cells and in melanocytes of the early passages (n/c NGF = 0.16-0.18), NGF slightly activated RNA synthesis but was without any effect on cell growth. At passage 5-6 of melanocytes (n/c NGF = 0.88), NGF inhibited RNA synthesis, which led to inhibition of cell growth. Removal of TPA from the culture of nevus cells resulted in increased n/c NGF ratio and in a switch from activatory to inhibitory action of NGF. The possibility that the cell surface receptor mediated the stimulatory effect of NGF and may antagonize the chromatin receptor-mediated inhibitory effect of NGF of melanocyte and nevus cell growth is discussed.
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PMID:Nerve growth factor chromatin receptor and cell surface receptor-regulated growth of melanocytes and nevus cells. 127 47

Immunohistochemical localization of nerve growth factor (NGF) receptor in normal skin and melanocytic tumor was analysed using monoclonal antibody. In normal skin and fetal skin NGF receptor was good marker for cutaneous nerve sheath and schwann cells. In melanocytic lineage, the NGF receptor was not expressed in fetal, normal and dermal melanocyte and weakly positive in only small part of nevus cell nest. Positive staining was seen in primary and metastatic melanoma lesion and restricted to melanoma cell membrane. The distribution of the receptor suggests that the NGF-receptor may be involved in the control of proliferation and malignant transformation in melanocytic lineage.
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PMID:[Expression of nerve growth factor-receptor in normal skin and melanocytic tumor]. 216 92

The murine nerve growth factor, when injected i.v. or, combined in vitro with plasma, was found largely associated with the mouse alpha-macroglobulin (a homologue of human alpha 2-macroglobulin). The nerve growth factor-alpha-macroglobulin complex produced is sufficiently stable to resist separation by gel filtration in 1.0 M sodium chloride, polyacrylamide gel electrophoresis, and immunoprecipitation by antibodies against alpha-macroglobulin. As determined by equilibrium binding studies and computer generated Scatchard analysis, alpha-macroglobulin apparently possesses two types of binding sites with the apparent dissociation constants of 1.2 x 10(-6) and 2.9 x 10(-9) M, respectively, saturable by 3.7 and 0.03 moles of nerve growth factor. Hence, about one mole of nerve growth factor is bound to each of the four subunits of alpha-macroglobulin. Nerve growth factor can be readily dissociated from alpha-macroglobulin in sodium dodecyl sulfate gel electrophoresis in the absence of a reductant. Procedures that affect the proteinase-binding or methylamine- activities of alpha-macroglobulin do not affect the binding of nerve growth factor, and the binding is unaffected by the presence of zinc ions or EDTA. Hence, nerve growth factor is noncovalently associated with alpha-macroglobulin at a site separate from that of the proteinase-, methylamine-, and zinc-binding sites of alpha-macroglobulin. Mouse alpha-macroglobulin can protect the nerve growth factor from inactivation by trypsin. Even in the presence of trypsin, alpha-macroglobulin-nerve growth factor complexes still can stimulate the neurite outgrowth by dorsal root ganglia of 9-day-old chicken embryos. Since alpha-macroglobulin can specifically and noncovalently carry nerve growth factor, one important role of this alpha-macroglobulin in the circulation and extracellular spaces may be to protect the nerve growth factor from proteinase inactivation.
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PMID:Interaction of nerve growth factor with murine alpha-macroglobulin. 246 89

7S nerve growth factor (7S NGF) and nerve growth factor I (NGFI) are NGF-containing protein complexes isolated from mouse submandibular glands by different protocols, and reports suggest that the molecules differ chemically. In this study, we compared the molecular properties and subunit compositions of the two proteins. Purified 7S NGF and NGFI electrophoresed to identical positions on polyacrylamide gels in nondissociating buffers, with electrophoretic mobilities indistinguishable from that of unpurified NGF in salivary gland extracts. Ultraviolet absorption curves were identical, and sedimentation coefficients were similar (7.3 +/- 0.25 S for 7S NGF; 7.2 +/- 0.2 S for NGFI) as determined by sedimentation velocity analysis. By sedimentation equilibrium analysis, molecular weights of 135 000-140 000 were obtained for both complexes at protein concentrations in the centrifuge cell greater than 85 micrograms/mL; when protein concentrations within the centrifuge cell ranged from approximately 30 to 100 micrograms/mL at equilibrium, both complexes dissociated. Molecular weight values determined by gel filtration on Bio-Gel P300 and Sephadex G200 resins were similar for both proteins, and the values determined on Sephadex agreed with those obtained by ultracentrifugation. The subunit compositions of the complexes were also similar as determined by nonequilibrium isoelectric focusing, NGFI being composed of proteins that migrated to positions identical with those of the alpha, beta, and gamma subunits of 7S NGF. Furthermore, the stoichiometry of the subunits was similar in the two complexes as determined by radioimmunoassays to each of the subunits and by densitometric analysis of electrophoretic gels. Both methods showed that the complexes contain approximately 2 mol of the alpha and gamma subunits per mole of beta-NGF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of 7S nerve growth factor and nerve growth factor I from mouse submandibular glands. 396 41

Iodination of the beta nerve growth factor protein up to 4.1 iodines per mole of nerve growth factor was achieved with no loss of biological activity. At this level of incorporation no native or monoiodo nerve growth factor remained, the major species being the tri- and tetraiodo derivatives. An (125)I-labeled beta nerve growth factor of high specific activity containing 0.5 iodine per mole of beta nerve growth factor was used to determine the specific binding of nerve growth factor to dorsal root ganglion cells of 8-day-old embryonic chicks. The specific binding of (125)I-labeled nerve growth factor reached saturation at 30-50 ng/ml and half-saturation at 7-8 ng/ml (0.26 nM). The number of receptors per responsive medio-dorsal cell was calculated to be about 2 x 10(4). The pattern of displacement of bound (125)I-labeled beta nerve growth factor by native beta nerve growth factor showed that the two proteins had identical affinities for the receptor. The specificity of the binding for beta nerve growth factor was demonstrated by the fact that only native beta nerve growth factor displaced the bound (125)I-labeled form. Partially inactivated derivatives of beta nerve growth factor retained the same fraction of their specific-binding capacity as of their biological activity. The specificity of the binding for cell type was shown by the lack of any specific component of (125)I-labeled beta nerve growth factor binding to liver or brain cells. The rate constant for association of beta nerve growth factor with its receptor, k(1), was 1.0 x 10(7) mol(-1) sec(-1) and the rate constant for dissociation, k(-1), 1.2 x 10(-8) sec(-1).
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PMID:Properties of the beta nerve growth factor receptor of avian dorsal root ganglia. 435 93

The nerve growth factor (NGF) receptor was characterized by using a new series of anti-receptor monoclonal antibodies (MAbs). These MAbs (i) showed significantly greater reactivity with a melanoma cell line expressing higher levels of NGF receptor, (ii) inhibited the binding of 125I-labeled NGF to its receptor, and (iii) immunoprecipitated both metabolically labeled and 125I-labeled NGF affinity-labeled receptor. These experiments defined the receptor as a 75-kDa cell-surface protein. The NGF receptor was visualized by immunoperoxidase staining in tissue sections of human nevi, melanomas, neurofibromas, a pheochromocytoma, and peripheral nerves. Uniform staining of the cytoplasm suggests that, in addition to cell-surface NGF receptors, there is a population of intracellular receptors.
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PMID:Characterization of nerve growth factor receptor in neural crest tumors using monoclonal antibodies. 609 11

Methylamine-modified alpha-2-macroglobulin (MA-alpha 2M) has been recently shown to inhibit the biological activity of beta-nerve growth factor (NGF) in promoting neurite outgrowth by embryonic dorsal root ganglia in culture (Koo PH, Liebl DJ, J Neurosci Res 31:678-692, 1992). The objectives of this study are to determine whether alpha 2M can also be modified by larger aromatic biogenic amines such as 5-hydroxytryptamine (5HT; serotonin), the nature of interaction between NGF and 5HT-modified alpha-2-M (5HT-alpha 2M), and the effect of 5HT-alpha 2M on the neurite extension and the growth of embryonic sensory and cholinergic neurons in 2 disparate animal species (chicken and rats). This study demonstrates that each mole of alpha 2M can combine with 15.2 +/- 1.8 moles of 5HT, in which up to 4.5 +/- 0.4 moles may be covalently bonded. As determined by gel filtration and polyacrylamide gel electrophoresis studies, both 5HT-alpha 2M and normal alpha 2M combine noncovalently with NGF, but 5HT-alpha 2M by comparison can combine with NGF somewhat more effectively. In contrast to normal alpha 2M, 5HT-alpha 2M at concentrations greater than about 0.17 microM exerts a dose-dependent inhibition on the NGF-stimulated neurite outgrowth by embryonic dorsal root ganglia and dissociated cells in culture, and the inhibitory effect can be overcome by higher NGF concentrations. Both 5HT-alpha 2M and MA-alpha 2M at 1.0 microM inhibit neurite extension by embryonic rat cerebral cortical cells and seriously damage these cells in culture. Such neurite-inhibitory activity, however, can only be partially blocked by extraneously added NGF alone. Normal alpha 2M (at 1.0 microM) and 5HT (at 188 microM), on the other hand, under the identical conditions produce very little or no effect on the normal cellular and axonal growth of these cells. We conclude that alpha 2M can potentially interact with nucleophilic monoamines, including neurotransmitters, to form inhibitory complexes which may inhibit/regulate NGF-promoted neurite outgrowth and neuronal survival. In addition, higher concentrations of such complexes can seriously damage certain CNS neurons which do not depend solely on NGF for survival.
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PMID:Serotonin-activated alpha 2-macroglobulin inhibits neurite outgrowth and survival of embryonic sensory and cerebral cortical neurons. 768 85

The histogenesis of "nevic corpuscles" (NCs) in neural nevi is still controversial. Recent studies have revealed that nerve growth factors (NGFs) and other growth factors [that is, epidermal growth factor (EGF)] could have various paracrine and autocrine functions on Schwann cells and melanocytes. We examined the immunohistochemical expression of NGF and EGF receptors (r) in 15 cases of neural nevi containing NCs along with 37 cases of other benign and malignant melanocytic lesions without neural differentiation (total, 52). Section were prepared from formalin-fixed and paraffin-embedded tissues. Monoclonal antibodies to NGFr and EGFr were used with the Avidin-biotin-complex (ABC) technique. We found strong reactivity for NGFr in 14 of 15 neural nevi with a predilection for NCs, but only eight of 37 were positive in the other group of melanocytic lesions without neural differentiation (four Spitz nevi, two melanomas, and two compound nevi). EGFr expression was limited mainly to NCs in four cases of neural nevi. We conclude that neural differentiation and NC formation are associated with NGFr overexpression, whereas EGFr expression is only limited. The relative paucity of NGFr expression in other type of benign and malignant melanocytic lesions supports the view that neural "differentiation" is a distinct process in certain long-standing melanocytic nevi. We postulate that NGFr overexpression may be the result of the reactivation of oncofetal genes that could become manifest in either abnormal schwannian differentiation (as seen in neural nevi), in a neoplastic context (as seen in neural and melanocytic tumors).
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PMID:Expression of nerve growth factor and epidermal growth factor receptors in neural nevi with nevic corpuscles. 890 91

Aluminum inactivated glutamate dehydrogenase (GDH) by a pseudo-first-order reaction at micromolar concentrations. A double-reciprocal plot gave a straight line with a k(inact) of 2.7 min(-1) and indicated the presence of a binding step prior to inactivation. The inactivation was strictly pH dependent and a marked increase in sensitivity to aluminum was observed as the pH decreased. At a pH higher than 8.5, no inactivation was observed. The completely inactivated GDH contained 2 mol of aluminum per mole of enzyme subunit monomer. When preincubated with enzyme, several chelators such as citrate, NaF, N-(2-hydroxyethyl) ethylenediaminetriacetic acid or ethylenediaminetriacetic acid efficiently protected the enzyme against the aluminum inactivation. In a related experiment, only citrate and NaF released the aluminum from the completely inactivated aluminum-enzyme complex and fully recovered the enzyme activity. Ferritin, NADP+, or nerve growth factor did not show any effects on the recovery of the aluminum-inactivated GDH activity. The dissociation constant for the aluminum-enzyme complex was calculated to be 5.3 microM. Although aluminum has been known to form a complex with nucleotides, no such effects were observed in the inactivation of GDH by aluminum as determined using GDHs mutated at the ADP-binding site, NAD+-binding site or GTP-binding site. Circular dichroism studies showed that the binding of aluminum to the enzyme induced a decrease in alpha helices and beta sheets and an increase in random coil. Therefore, inactivation of GDH by aluminum is suggested to be due to the conformational change induced by aluminum binding. These results suggest a possibility that aluminum-induced alterations in enzymes of the glutamate system may be one of the causes of aluminum-induced neurotoxicity.
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PMID:Inactivation of human glutamate dehydrogenase by aluminum. 1462 97


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