PS-990, a novel microbial metabolite, reversibly induces neurite extension in neuroblastoma cells.
PS-990, which is a novel microbial metabolite, induced neurite formation in a murine neuroblastoma cell line, Neuro2A. In the presence of PS-990 at 30 micrograms/ml, significant neurite outgrowth was observed. Cultures maintained for 12 h in the presence of PS-990 resulted in the maximal number of neurite-bearing cells, and then the neurites formed were gradually retracted. The retracted cells again yielded the neurite formation when the cells were exposed again to PS-990. PS-990 inhibited both the cell growth and thymidine incorporation into the cells at the same concentration range. Although the type of neurite formation with PS-990 is similar to that with a cyclic AMP analog and indeed PS-990 has an inhibitory potency against calcium and calmodulin-dependent cyclic nucleotide phosphodiesterase, the intracellular cyclic AMP level was not elevated when treated with PS-990. These results suggest that PS-990 reversibly induces neurite formation with arrest of the cell growth through a mechanism distinct from an increase in the intracellular cyclic AMP concentration.
Toki
S
S
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Japan.
Yoshida
M
M
Ando
K
K
Matsuda
Y
Y
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000164:Acremonium / Q000378:metabolism; D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology / Q000648:ultrastructure*; D002147:Calmodulin / Q000378:metabolism; D003470:Culture Media; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D062385:Hydroxybenzoates / Q000494:pharmacology*; D051379:Mice; D016501:Neurites / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D009447:Neuroblastoma / Q000201:enzymology / Q000648:ultrastructure*; D016716:PC12 Cells; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002147:Calmodulin; D003470:Culture Media; D062385:Hydroxybenzoates; D010726:Phosphodiesterase Inhibitors; C091109:PS 990; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D013936:Thymidine