The effect of ER stress on activity-dependent induction of brain-derived neurotrophic factor exon III.
Neuronal activity promotes neuronal survival and increases synaptic strength. These effects are primarily mediated by influx of calcium through L-type calcium channels during membrane depolarization. This activates the transcription factor CREB by phosphorylating it on Ser-133 and induces several genes including BDNF exon III that play important roles in activity-dependent neuronal survival. Since ER stress is known to perturb intracellular calcium signaling, we examined whether it attenuated depolarization-induced CREB Ser-133 phosphorylation and BDNF exon III expression in PC12 cells. ER stress induced by tunicamycin, beta-mercaptoethanol, or thapsigargin did not reduce depolarization-induced CREB Ser-133 phosphorylation. However it did suppress the induction of BDNF exon III by membrane depolarization, indicating that it exerts this effect by blocking a pathway distinct from CREB Ser-133 phosphorylation.
Park
Ji Ae
JA
Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yongin 449-791, Korea.
Kwon
Hyockman
H
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002118:Calcium / Q000737:chemistry; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D005091:Exons; D008623:Mercaptoethanol / Q000494:pharmacology; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019284:Thapsigargin / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology
D019208:Brain-Derived Neurotrophic Factor; D020746:Calcium Channels, L-Type; D017362:Cyclic AMP Response Element-Binding Protein; D014415:Tunicamycin; D008623:Mercaptoethanol; D019284:Thapsigargin; D002118:Calcium