Apoptosis induced by protein kinase C inhibition in a neuroblastoma cell line.
The protein kinase C inhibitor bisindolylmaleimide GF109203X has a dual effect on the behavior of the neuroblastoma cell line Neuro-2A; when the inhibitor is added in conditions that induce differentiation (absence of serum), neurite outgrowth is potentiated in a dose-dependent manner. However, if the inhibitor is added in growth-promoting conditions (presence of serum), programmed cell death (apoptosis) is induced, as assessed by internucleosomal DNA cleavage and specific immunoassays. This effect is also seen with other specific protein kinase C inhibitors. Bcl2 gene overexpression protects Neuro-2A cells from apoptosis, as has been found in other systems. We also show that calpain I, a neutral Ca(2+)-activated proteinase, participates in this apoptotic pathway. Our results point to a key role of protein kinase C in the regulation of growth and differentiation in Neuro-2A cells.
Behrens
M M
MM
Institute of Biomedical Investigations, Cosejo Superior de Investigaciones Científicas, CSIC, Department of Biochemistry, Universidad Autónoma de Madrid, Spain.
Martínez
J L
JL
Moratilla
C
C
Renart
J
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001798:Blood Proteins / Q000494:pharmacology; D002154:Calpain / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000502:physiology; D007211:Indoles / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology*; D051379:Mice; D009447:Neuroblastoma; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D014407:Tumor Cells, Cultured / Q000166:cytology
D001798:Blood Proteins; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D002154:Calpain; C070515:bisindolylmaleimide I