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)

Pipecolic acid, a lysine metabolite, is thought to be a factor responsible for hepatic encephalopathy; however, the underlying mechanism is far from understood. Twenty minutes treatment with D-, L-, and DL-pipecolic acid at concentrations ranging from 1 to 100 microM, except for 1 microM L-pipecolic acid, had no inhibitory effect on excitatory postsynaptic responses in the dentate gyrus of rat hippocampal slices. In a whole-cell voltage-clamp configuration, DL-pipecolic acid (10 and 100 microM) did not affect voltage-sensitive Na(+) channel currents and K(+) channel currents, but it potentiated voltage-sensitive Ca(2+) channel currents, but to a lesser extent, in cultured rat cortical neurons and Neuro-2A cells, a mouse neuroblastoma cell line. Notably, 72-h treatment with D-, L-, and DL-pipecolic acid reduced Neuro-2A cell viability in a dose-dependent manner at concentrations ranging from 1 to 100 microM in a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, in parallel with reactions to propidium iodide, a marker of cell death, and Hoechst 33,342, a marker of apoptosis in a fluorescent microscopic study, with DL-pipecolic acid being the most potent. The results of the present study suggest that pipecolic acid could cause hepatic encephalopathy by inducing neuronal cell death, perhaps apoptosis, rather than by depressing neurotransmissions.
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PMID:Pipecolic acid induces apoptosis in neuronal cells. 1286 56

High blood levels of ammonium/ammonia (NH(4)(+)/NH(3)) are associated with severe neurotoxicity as observed in hepatic encephalopathy (HE). Astrocytes are the main targets of ammonium toxicity, while neuronal cells are less vulnerable. In the present study, an astrocytoma cell line 1321N1 and a neuroblastoma glioma hybrid cell line NG108-15 were used as model systems for astrocytes and neuronal cells, respectively. Ammonium salts evoked a transient increase in intracellular calcium concentrations ([Ca(2+)](i)) in astrocytoma (EC(50)=6.38 mM), but not in NG108-15 cells. The ammonium-induced increase in [Ca(2+)](i) was due to an intracellular effect of NH(4)(+)/NH(3) and was independent of extracellular calcium. Acetate completely inhibited the ammonium effect. Ammonium potently reduced calcium signaling by G(q) protein-coupled receptors (H(1) and M3) expressed on the cells. Ammonium (5 mM) also significantly inhibited the proliferation of 1321N1 astrocytoma cells. While mRNA for the mammalian ammonium transporters RhBG and RhCG could not be detected in 1321N1 astrocytoma cells, both transporters were expressed in NG108-15 cells. RhBG and RhBC in brain may promote the excretion of NH(3)/NH(4)(+) from neuronal cells. Cellular uptake of NH(4)(+)/NH(3) was mainly by passive diffusion of NH(3). Human 1321N1 astrocytoma cells appear to be an excellent, easily accessible human model for studying HE, which can substitute animal studies, while NG108-15 cells may be useful for investigating the role of the recently discovered Rhesus family type ammonium transporters in neuronal cells. Our findings may contribute to the understanding of pathologic ammonium effects in different brain cells, and to the treatment of hyperammonemia.
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PMID:Ammonium-induced calcium mobilization in 1321N1 astrocytoma cells. 1806 Dec 26