The rescuing effect of nerve growth factor is the result of up-regulation of bcl-2 in hyperoxia-induced apoptosis of a subclone of pheochromocytoma cells, PC12h.
The rat pheochromocytoma cell line PC12 is useful for studying neuronal cell differentiation since this cell line differentiates into neuron-like cells in response to nerve growth factor (NGF). We demonstrated that PC12h cells, a subclone of PC12 cells, died under hyperoxia (50% O2). This cell death did not occur in the presence of antioxidant reagents. In the dead cells, DNA fragmentation and chromatin condensation were observed, suggesting that hyperoxia-induced apoptosis via reactive oxygen species (ROS). NGF effectively suppressed this hyperoxia-induced apoptosis. Accordingly, the amounts of bcl-2, a proto-oncogene product, increased in the cells rescued from apoptosis by NGF. Furthermore, bcl-2 antisense oligonucleotide canceled this rescuing effect of NGF. The present findings indicate that NGF rescues PC12h cells from hyperoxia-induced apoptosis via up-regulation of bcl-2.
Katoh
S
S
Radiation Safety Office, University of Tokyo Hospital, Japan.
Mitsui
Y
Y
Kitani
K
K
Suzuki
T
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D018496:Hyperoxia / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects*
D009414:Nerve Growth Factors; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2