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)

A variety of compounds were assessed for their ability to induce morphological differentiation and to affect the synthesis of RNA in uncloned mouse neuroblastoma cells in culture. The stimulation of morphological differentiation in uncloned cells after exposure for 48 hours to concentrations of 3 times 10-7 to 3 times 10-4 M papavarine or 10-9 to 10-3 M dibutyryl adenosine 3':5'-monophosphate (dibutyryl-cAMP) was associated, in part, with a concentration-dependent decrease in incorporation of [5-3H]uridine into ribosomal RNA (rRNA) and heterogeneous RNA (HnRNA). The latter effect on cellular RNA produced by papavarine occurred within 1 hour after its addition to the medium and was associated with impaired uptake of radioactive precursor into uridine nucleotides and reduction in the intracellular concentration of uridine 5'-triphosphate (UTP). Dibutytyl-cAMP produced a decreased in the specific radioactivity of UTP without affecting the concentration of UTP in the tumor cells. The effects of papavarine and dibutyryl-cAMP could be distinguished further by the 50% reduction of acetylcholinesterase activity produced by papavarine, but not by dibutyryl-cAMP. Papavarine did not, however, reduce the cellular level of the soluble enzyme, adenine phosphoribosyltransferase. Sodium butyrate, while producing morphological effects similar to those of papavarine and dibutyryl-cAMP at equimolar concentrations, caused no significant changes in the incorporation of [5-3H]uridine into rRNA and HnRNA; however, acetylcholinesterase activity was stimulated 6- to 7-fold above control levels. In contrast to the other differentiating agents examined, addition of 10-9 to 3 times 10-4 M concentrations of cAMP to the tissue culture medium enhanced morphological differentiation of nueroblastoma cells, and caused a 10- to 20-fold stimulation of the incorporation of [5-3H]uridine into rRNA and HnRNA at concentrations of 10-4 M and higher. This effect observed only at high concentrations of cyclic nucleotide was accompanied by an elevation in the specific acitivty of UTP, These studies suggest that the morphological response of neuroblastoma cells is not necessarily associated with concomitant alterations in the synthesis of RNA with agents other than cAMP. Observed changes in incorporation of [5-3H]uridine into RNA appear in most instances to be due to alterations in the uptake of uridine, and in the pool size and specific radioactivity of UTP.
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PMID:Effects of adenosine 3':5'-monophosphate and related agents on ribonucleic acid synthesis and morphological differentiation in mouse neuroblastoma cells in culture. 16 51

Giardia lamblia, a flagellated parasitic protozoan and the causative agent of giardiasis, lacks de novo purine biosynthesis and exists on salvage of adenine and guanine by adenine phosphoribosyltransferase and guanine phosphoribosyltransferase. Guanine phosphoribosyltransferase from G. lamblia crude extracts has been purified to apparent homogeneity by Sephacryl S-200 gel filtration followed by C-8-GMP-agarose and 2',3'-GMP-agarose affinity chromatography, resulting in an overall recovery of 77% and a purification of 83,000-fold. The molecular weight of the native enzyme as estimated by gel filtration and isokinetic sucrose gradients was found to be 58,000-63,000, with a subunit molecular weight of approximately 29,000, as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Mono P chromatofocusing chromatography gives rise to a major activity peak eluting from the column at a pH of 6.75 and two minor activity peaks at pH of 5.3 and 5.2. Hypoxanthine and xanthine can be recognized by the enzyme as substrates but at Km values 20 times higher than that observed with guanine. G. lamblia guanine phosphoribosyltransferase is immunologically distinct from human hypoxanthine-guanine phosphoribosyltransferase and Escherichia coli xanthine-guanine phosphoribosyltransferase, and G. lamblia DNA fragments are incapable of hybridizing with mouse neuroblastoma hypoxanthine-guanine phosphoribosyltransferase DNA or E. coli xanthine phosphoribosyltransferase DNA under relatively relaxed conditions. All evidence presented suggests that G. lamblia guanine phosphoribosyltransferase may be qualified as a potential target for antigiardiasis chemotherapy.
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PMID:Purification and characterization of guanine phosphoribosyltransferase from Giardia lamblia. 308 75