RRC ID 39376
Author Katoh S, Mitsui Y, Kitani K, Suzuki T.
Title Hyperoxia induces the neuronal differentiated phenotype of PC12 cells via a sustained activity of mitogen-activated protein kinase induced by Bcl-2.
Journal Biochem. J.
Abstract We previously reported that rat pheochromocytoma PC12 cells express the neuronal differentiated phenotype under hyperoxia through the production of reactive oxygen species (ROS). In the present study, we found that in this phenotype, Bcl-2, an apoptosis inhibitor, affects mitogen-activated protein (MAP)-kinase activity, which is known as a key enzyme of the signal-transduction cascade for differentiation. When PC12 cells were cultured under hyperoxia, a rapid increase in MAP-kinase activity, including that of both p42 and p44, was observed. Although the activity level then decreased quickly, activity higher than the control level was observed for 48 h. PD98059, an inhibitor of MAP kinase, suppressed the hyperoxia-induced neurite extensions, suggesting the involvement of MAP-kinase activity in the mechanism of differentiation induced by ROS. An elevation of Bcl-2 expression was observed after culturing PC12 cells for 24 h under hyperoxia. This Bcl-2 elevation was not affected by treatment with PD98059, suggesting that it did not directly induce neurite extension under hyperoxia. However, the blockade of the Bcl-2 elevation by an antisense oligonucleotide inhibited the sustained MAP-kinase activity and neurite extensions under hyperoxia. Further, in PC12 cells highly expressing Bcl-2, the sustained MAP-kinase activity and neurite extensions under hyperoxia were enhanced. These results suggested that MAP kinase is activated through the production of ROS, and the subsequent elevation of Bcl-2 expression sustains the MAP-kinase activity, resulting in the induction of the neuronal-differentiation phenotype of PC12 cells under hyperoxia.
Volume 338 ( Pt 2)
Pages 465-70
Published 1999-3-1
PMID 10024524
PMC PMC1220074
MeSH Animals Base Sequence Calcium-Calmodulin-Dependent Protein Kinases / biosynthesis Calcium-Calmodulin-Dependent Protein Kinases / metabolism* Cell Differentiation Enzyme Induction Hyperoxia / metabolism* Neurites / drug effects Neurons / cytology* Oligonucleotides, Antisense / pharmacology PC12 Cells Phenotype Proto-Oncogene Proteins c-bcl-2 / genetics Proto-Oncogene Proteins c-bcl-2 / metabolism* Rats Reactive Oxygen Species
IF 4.331
Times Cited 31
Human and Animal Cells