Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of angiotensin II on the cytosolic free Ca2+ concentration was measured in single mouse neuroblastoma N1E-115 cells loaded with fura-2. Angiotensin II induced a transient concentration-dependent increase in Ca2+ and also increased the production of inositol polyphosphates. The Ca2+ increase did not require extracellular Ca2+ and was unaffected by pretreatment with pertussis toxin. These data suggest that angiotensin II increased Ca2+ by an inositol trisphosphate-mediated release of intracellular Ca2+ following activation of phospholipase C via a pertussis toxin-insensitive guanine nucleotide binding protein. Similar results were obtained with bradykinin. The angiotensin II- or bradykinin-induced increase in Ca2+ occurred after a concentration-dependent latent period. Low concentrations of agonist elicited a small increase in Ca2+ following a variable lag that sometimes exceeded 1 min, whereas at maximally effective angiotensin II concentrations a larger, more rapid increase in Ca2+ occurred without a measurable delay. In some cells, oscillatory increases in Ca2+ were induced by angiotensin II and bradykinin. Possible mechanisms to explain the concentration dependency of the latent period and the oscillatory nature of the increases of Ca2+ are discussed. These results indicate that the mouse neuroblastoma N1E-115 cell represents a useful model for studying the signal response transduction mechanisms regulating the effects of angiotensin II in neuronal cells.
 ...
PMID:Angiotensin II effects on the cytosolic free Ca2+ concentration in N1E-115 neuroblastoma cells: kinetic properties of the Ca2+ transient measured in single fura-2-loaded cells. 229 17

The murine neuroblastoma N1E-115 cell line contains binding sites for the angiotensin II (Ang II) receptor antagonist 125I-[Sarc1,Ile8]-Ang II (125I-SARILE). Binding of 125I-SARILE to N1E-115 membranes was rapid, reversible, and specific for Ang II-related peptides. The rank order potency of 125I-SARILE binding was the following: [Sarc1]-Ang II = [Sarc1,Ile8]-Ang II greater than Ang II greater than Ang III = [Sarc1,Thr8]-Ang II much greater than Ang I. Scatchard analysis of membranes prepared from confluent monolayers revealed a homogenous population of high affinity (KD = 383 +/- 60 pM) binding sites with a Bmax of 25.4 +/- 1.6 fmol/mg of protein. Moreover, the density, but not the affinity, of the binding sites increased as the cells progressed from logarithmic to stationary growth in culture. Finally, agonist, but not antagonist, binding to N1E-115 cells was regulated by guanine nucleotides. Collectively, these results suggest that the murine neuroblastoma N1E-115 cell line may provide a useful model in which to investigate the signal transduction mechanisms utilized by neuronal Ang II receptors.
 ...
PMID:Characterization of binding sites for the angiotensin II antagonist 125I-[Sarc1,Ile8]-angiotensin II on murine neuroblastoma N1E-115 cells. 270 10

High activity of renin was demonstrated in human neuroblastoma tissue. This activity was inhibited by specific antibody raised against human renal renin, indicating that it was not due to the nonspecific action of proteases. The specific activity of renin was 122.8 ng of angiotensin I generated mg of protein-1 h-1. It shared some biochemical features with well-known kidney renin, such as molecular weight, optimum pH, the presence of trypsin-activatable inactive renin, and glycoprotein nature. Furthermore, angiotensin-converting enzyme (ACE) activity (2.64 nmol mg of protein-1 min-1) was found in the tissue. This activity was inhibited by captopril, a specific ACE inhibitor, or by omission of chloride ion. These results suggest that true renin in addition to ACE exists in human neuroblastoma tissue.
 ...
PMID:Renin and angiotensin-converting enzyme in human neuroblastoma tissue. 298 31

A kinetic analysis of the tyrosine-specific protein kinase of pp60c-src from the C1300 mouse neuroblastoma cell line Neuro-2A and pp60c-src expressed in fibroblasts was carried out to determine the nature of the increased specific activity of the neuroblastoma enzyme. In immune-complex kinase assays with ATP-Mn2+ and the tyrosine-containing peptide angiotensin I as phosphoacceptor substrate, pp60c-src from the neuroblastoma cell line was characterized by a maximum velocity (Vmax.) that was 7-15-fold greater than the Vmax. of pp60c-src from fibroblasts. The neuroblastoma enzyme exhibited Km values for ATP (16 +/- 3 microM) and angiotensin I (6.8 +/- 2.6 mM) that were similar to Km values for ATP (25 +/- 3 microM) and angiotensin I (6.5 +/- 1.7 mM) of pp60c-src from fibroblasts. pp60v-src expressed in Rous-sarcoma-virus-transformed cells exhibited an ATP Km value (25 +/- 4 microM) and an angiotensin I Km value (6.6 +/- 0.5 mM) that approximated the values determined for pp60c-src in neuroblastoma cells and fibroblasts. These results indicate that the pp60c-src kinase from neuroblastoma cells has a higher turnover number than pp60c-src kinase from fibroblasts, and that the neural form of the enzyme would be expected to exhibit increased catalytic activity at the saturating concentrations of ATP that are found intracellularly.
 ...
PMID:Vmax. activation of pp60c-src tyrosine kinase from neuroblastoma neuro-2A. 332 40

Cells of the homogeneous hybrid line neuroblastoma x glioma (NG108-15) have many neuronal properties. Immunocytochemical tests show that they contain both immunoreactive renin and angiotensin; direct radioimmunoassays show that they are positive for renin, angiotensin I, and angiotensin II; enzymatic assays show that they contain angiotensinogen and converting enzyme as well. The renin appears to be present in an enzymatically inactive form that can be activated by trypsin and then blocked by antiserum to purified mouse submaxillary renin. Renin concentration and activity are increased by enhancing cellular differentiation with dibutyryl cyclic adenosine monophosphate or by serum withdrawal. These findings demonstrate a complete renin-angiotensin system within these neuron-like cells, and suggest that activation of intracellular renin could generate angiotensin II.
 ...
PMID:Renin and angiotensin: the complete system within the neuroblastoma x glioma cell. 627 92

Twenty years ago it was demonstrated that angiotensin II (Ang II) acts on the brain, which results in an elevation of blood pressure. Ten years later, reninlike activity was discovered in the brain of the rat and dog, which gave rise to the concept of an endogenous brain renin-angiotensin system. In the periphery, the kidney, liver, and lungs work in unison to produce Ang II. Evidence for brain renin, substrate, converting enzyme, and angiotensins is reviewed. New data indicate that the enzyme system for the synthesis of Ang II within the brain may in fact be contained in the cell. All the components for a renin-angiotensin system have now been found in neuroblastoma/glioma cell lines and Ang II is present in primary cell culture of rat brain neurons. The significance of angiotensin in the brain for hypertension is that it may be a stimulus for vasopressin release and sympathetic activation, which can maintain high blood pressure. In the spontaneously hypertensive rat, there is evidence of increased brain angiotensin. Also, experiments with angiotensin-converting enzyme inhibitors show that blockade of brain angiotensin production leads to a long-lasting lowering of blood pressure. The activity of the inhibitors in part appears to be directly on the brain.
 ...
PMID:New evidence for brain angiotensin and for its role in hypertension. 630 29

The renin-angiotensin system is an exception among the various peptide hormone producing mechanisms in that it is an extracellular system. It was not clear whether renin in tissues other than kidney participates in the extracellular system or an intracellular mechanism. We examined the possibility of intracellular formation of angiotensin II in these tissues by using cloned, renin containing cells in culture as models. Neuroblastoma cells, pheochromocytoma cells, adrenal cortical cells and juxtaglomerular cells were shown to contain renin, angiotensin I and angiotensin II. Presence of angiotensin I converting enzyme was also demonstrated in some cell lines examined. Even juxtaglomerular cells in the intact kidney were shown to contain angiotensin I and angiotensin II by immunohistochemical technique. These findings indicate an intracellular mechanism of angiotensin II formation in various tissues and suggest that angiotensin II may have local paracrine functions.
 ...
PMID:Local generation of angiotensin in the kidney and in tissue culture. 664 Sep 64

Although the brain contains cathepsins at high concentrations which exhibit a non-specific renin-like activity at acidic pH, the presence of specific renin in the brain has been demonstrated by characterizing its specific properties. Renin was separated from cathepsin by affinity chromatography on casein-Sepharose. Brain renin showed neutral pH optima for the reaction to generate angiotensin I. The presence of inactive prorenin was also found. The isoelectric points of brain renin were significantly lower differences from that of renal or plasma renin. Immunohistochemical studies demonstrated a wide-spread localization of renin in many different regions. Angiotensin II, the final product of the prohormone-to-hormone conversion reaction mediated by renin and angiotensin converting enzyme, was found to exist in the same cell as renin by immunohistochemical studies of brain sections and with cloned and cultured neuroblastoma cells. This is the first demonstration of the mechanism of peptide hormone formation in neuronal cells. Similar intracellular formation was demonstrated in gonadotrophs of adenohypophysis. Coexistence of renin and angiotensin II was demonstrated in some cells. Electrophysiological studies have shown that angiotensin II functions to disinhibit the inhibition of neuronal response to electrical stimuli in the hippocampus.
 ...
PMID:Brain renin. 704 40

Murine N1E-115 neuroblastoma cells are shown to express a single class of angiotensin II (Ang II) receptors that display all the pharmacological properties defining the Ang II receptor subtype 2 (AT2): high affinity for 125I-labelled AT2-selective agonist CGP 42112 (Kd 91 +/- 19 pM); expected rank order of potency (CGP 42112 = (Sar1,Ile8)Ang II > or = Ang II > PD 123319 >> DUP 753) for several Ang II analogues; increased binding in the presence of the reducing reagent dithiothreitol (DTT); and insensitivity to analogues of GTP. Molecular cloning of cDNA encoding AT2 receptors from N1E-115 cells reveals nucleotide sequence identity with the AT2 subtype expressed in fetal tissue. Murine AT2 receptors transiently expressed in COS cells display the same pharmacological profile as endogenous Ang II receptors of N1E-115 cells. Taken together, these data reveal the exclusive presence of the AT2 receptor subtype in N1E-115 cells. Incubation of N1E-115 cells with Ang II leads to a marked decrease in the level of tyrosine phosphorylation of several proteins with apparent molecular masses of 80, 97, 120, 150 and 180 kDa respectively. Tyrosine dephosphorylation of the same set of proteins is observed after treatment with the AT2-specific agonist CGP 42112. The response to both effectors is rapid and transient, showing a maximum between 5 and 10 min, and returning to basal levels after 20-30 min. In both cases, tyrosine dephosphorylation can be prevented by co-incubation with an excess of the antagonist Sarile. These data thus establish that AT2 receptor activation leads to protein tyrosine dephosphorylation in N1E-115 cells, and support a possible role for AT2 receptors in the negative regulation of cell proliferation.
 ...
PMID:Angiotensin II AT2 receptors are functionally coupled to protein tyrosine dephosphorylation in N1E-115 neuroblastoma cells. 753 1

A stable cell line expressing the angiotensin II (AII) receptor has been obtained by transfecting the human neuroblastoma SH-SY5Y with the plasmid pCEP4 containing the entire coding region of the rat angiotensin AII receptor AT1A. Angiotensin II (AII; 1-100 nM) evokes the release of [3H]noradrenaline ([3H]NA) in this cell line. Pretreatment with 100 nM 12-O-tetradecanoylphorbol-13-acetate (TPA) enhances the AII-evoked release of [3H]NA approximately two-fold. Removal of extracellular Ca2+ ([Ca2+]o) decreases 100 nM AII-evoked release of [3H]NA by over 50% both in the presence and absence of TPA. AII increases intracellular Ca2+ ([Ca2+]i) in this cell line which is consistent with the AT1A receptor being coupled to phospholipase C. Pretreatment with 100 nM TPA for 8 min attenuated the effect of AII on [Ca2+]i. The effects of AT1A receptor stimulation are therefore regulated differently in this cell line by activation of protein kinase C (PKC). Thus a useful cell line has been obtained from the human neuroblastoma SH-SY5Y in which to study at the molecular level the mechanism(s) by which AII regulates NA release.
 ...
PMID:The effect of the angiotensin II (AT1A) receptor stably transfected into human neuroblastoma SH-SY5Y cells on noradrenaline release and changes in intracellular calcium. 858 37


<< Previous 1 2 3 Next >>