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

The effects of chemotherapy on living tumor tissue in hamsters and rats were investigated by measuring the 31P nuclear magnetic resonance spectra using topical magnetic resonance. Human neuroblastoma, human glioblastoma, and rat glioma tumor cells were inoculated s.c. in the lumbar region of the animals. After the diameter of the tumors increased to 1.5 cm, in vivo 31P nuclear magnetic resonance spectra were measured selectively in the tumors with a TMR-32 spectrometer. Adenosine triphosphate, inorganic phosphate (Pi), phosphodiester, and phosphomonoester peaks were observed. The phosphocreatine peak was hardly detectable, adenosine triphosphate and phosphomonoester peaks were high, and tissue pH, calculated from the chemical shift of Pi, declined. Regardless of the tumor origin or the histological type, the spectral pattern of each neuroectodermal tumor was found to be essentially the same. After i.v. injection of a large dose of a chemotherapeutic agent, adenosine triphosphate peaks decreased and Pi increased gradually, resulting in a dominant Pi peak pattern after 6 to 12 hours. However, during the same period, there were no observable changes in the spectra of normal organs. These findings indicated that the drugs have a selective and direct action on the energy metabolism of tumor cells. With lower drug doses, no remarkable changes were seen in the spectrum. Measurement of in vivo 31P nuclear magnetic resonance spectra is valuable not only to investigate the energy metabolism in tumor tissue but also to evaluate the effects of chemotherapy.
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PMID:Measurements of in vivo 31P nuclear magnetic resonance spectra in neuroectodermal tumors for the evaluation of the effects of chemotherapy. 398 84

Adenosine triphosphate (ATP) regulates surfactant phospholipid secretion from alveolar type II cells by interacting with P2-purinoceptors on the alveolar type II cell surface. To further characterize regulation of surfactant secretion, we have cloned the type II cell P2u-purinoceptor and expressed a functional receptor in an unrelated cell line. The coding sequence of the P2u clone isolated from a type II cell cDNA library was 1.1 kb, encoding a putative protein of 374 amino acids. The putative protein demonstrated > 97% homology with the P2u-purinoceptor previously identified in the hybrid neuroblastoma x glioma cell line, NG 108-15, 87% homology to the recently cloned human P2u-purinoceptor, and 34% homology to the P2u-purinoceptor cloned from chicken brain. The putative type II cell P2u protein contains seven membrane-spanning domains, characteristic of G-protein-coupled receptors. The type II cell P2u-purinoceptor nucleotide sequence also demonstrated > 95% homology to the nucleotide sequence of the NG 108-15 clone. However, the type II cell cDNA also demonstrated presence of an additional 208 bp insert in the 5' untranslated region, which was not present in the NG 108-15 clone. Using reverse transcriptase polymerase chain reaction, we examined expression of the two different sizes of mRNA in various rat tissues. Only the larger type II cell mRNA was expressed in rat heart, kidney, lung, spleen, and testis, with no expression of P2u-purinoceptor mRNA noted in brain or liver. The smaller species of mRNA was only detected in mouse N18-TG2 cells, and these cells expressed a larger species as well, found in the rat tissues noted.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cloning and expression of the alveolar type II cell P2u-purinergic receptor. 781 68

Adenosine triphosphate (ATP) can be released in large amounts from (damaged) cells, leading to locally high concentrations. In this study, we investigated the effect of such high concentrations of ATP on neuroblastoma cells. ATP (>or=30 microM) induced apoptosis in the mouse neuroblastoma cell line N1E-115. Activation of the ATP receptor P2X(7) is one of the routes via which ATP has been shown to induce apoptosis. Although the P2X(7) receptor was present in N1E-115 cells, both at the protein and mRNA level, studies with the P2X(7) receptor agonist benzoyl-benzoyl ATP showed that this receptor was not involved in ATP-induced apoptosis. It has been shown previously that adenosine induces apoptosis in N1E-115 cells after transport inside the cell. In this study, both dipyridamole, a nucleoside transport protein blocker, and uridine, a substrate for this transporter, were able to block ATP-induced apoptosis. This indicated that ATP had to be broken down to adenosine to induce apoptosis. The ecto-nucleotidase inhibitors 6-N,N-diethyl-beta-dibromomethylene-D-adenosine-5'-triphosphate (ARL67156) and alpha,beta-methylene adenosine 5'-diphosphate (AOPCP) commonly used to slow breakdown of ATP did not inhibit ATP breakdown appreciably, while the ATP antagonist PPADS inhibited the breakdown of AMP to adenosine; PPADS was also the only compound capable of inhibiting ATP-induced apoptosis. We conclude that the main route of ATP-induced apoptosis in N1E-115 cells was via breakdown to adenosine.
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PMID:Apoptosis induced by extracellular ATP in the mouse neuroblastoma cell line N1E-115: studies on involvement of P2 receptors and adenosine. 1193 44

Adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels couple cellular metabolic status to membrane electrical activity. In this study, we performed patch-clamp recordings to investigate how cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) regulates the function of K(ATP) channels, using both transfected human SH-SY5Y neuroblastoma cells and embryonic kidney (HEK) 293 cells. In intact SH-SY5Y cells, the single-channel currents of Kir6.2/sulfonylurea receptor (SUR) 1 channels, a neuronal-type K(ATP) isoform, were enhanced by zaprinast, a cGMP-specific phosphodiesterase inhibitor; this enhancement was abolished by inhibition of PKG, suggesting a stimulatory role of cGMP/PKG signaling in regulating the function of neuronal K(ATP) channels. Similar effects of cGMP accumulation were confirmed in intact HEK293 cells expressing Kir6.2/SUR1 channels. In contrast, direct application of purified PKG suppressed rather than activated Kir6.2/SUR1 channels in excised, inside-out patches, while tetrameric Kir6.2LRKR368/369/370/371AAAA channels expressed without the SUR subunit were not modulated by zaprinast or purified PKG. Lastly, reconstitution of the soluble guanylyl cyclase/cGMP/PKG signaling pathway by generation of nitric oxide led to Kir6.2/SUR1 channel activation in both cell types. Taken together, here, we report novel findings that PKG exerts dual functional regulation of neuronal K(ATP) channels in a SUR subunit-dependent manner, which may provide new means of therapeutic intervention for manipulating neuronal excitability and/or survival.
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PMID:Dual regulation of the ATP-sensitive potassium channel by activation of cGMP-dependent protein kinase. 1823 7