Distinct isozyme patterns of cyclic nucleotide phosphodiesterase in human neuroblastoma and ganglioneuroma; a possible marker of differentiation of neural crest-derived tumors and Schwann cells.
By DEAE-cellulose chromatography, the 30,000g supernatants of human neuroblastoma (n = 7), ganglioneuroma (n = 5), sympathetic ganglia (n = 3), and Schwannoma (n = 2) were found to contain three major peaks of adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase (PDE) activity, which were termed peaks I, II, and III in the order of their elution from the column. Peak I isozyme was calmodulin-dependent, and had two different Km values for cAMP (32 and 2.3 microM) and a low Km for guanosine 3',5'-cyclic monophosphate (cGMP) (2.9 microM). Peak II isozyme had a high Km for both cAMP, 76 microM, and cGMP, 32 microM, and peak III isozyme was a cAMP-PDE with Km of 1.8 microM. The peak II and III isozymes were calmodulin-independent. The activity ratio of peak I isozyme to peak III isozyme (I/III isozyme ratio) was significantly different (P less than 0.001) in neuroblastoma and in ganglioneuroma/sympathetic ganglia, i.e., 0.23 +/- 0.11 for neuroblastoma vs. 0.79 +/- 0.20 for ganglioneuroma and 0.51 +/- 0.08 for sympathetic ganglia. Schwannoma showed the highest value of 1.05 (P less than 0.05). These results suggest that the I/III isozyme ratio of cAMP-PDE could be a useful marker in studies on the differentiation of neural crest-derived tumors and Schwann cells.
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000032:analysis*; D002147:Calmodulin / Q000494:pharmacology; D002454:Cell Differentiation; D002848:Chromatography, DEAE-Cellulose; D005729:Ganglioneuroma / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000032:analysis*; D007700:Kinetics; D009432:Neural Crest / Q000201:enzymology*; D009447:Neuroblastoma / Q000201:enzymology*; D011480:Protease Inhibitors / Q000494:pharmacology; D012583:Schwann Cells / Q000201:enzymology*
D002147:Calmodulin; D007527:Isoenzymes; D011480:Protease Inhibitors; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases