PMID- 12805282 OWN - NLM STAT- MEDLINE DCOM- 20030701 LR - 20200225 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 23 IP - 11 DP - 2003 Jun 1 TI - Brain-derived neurotrophic factor protection of cortical neurons from serum withdrawal-induced apoptosis is inhibited by cAMP. PG - 4420-7 AB - Programmed cell death plays an important role both during the development of the CNS and in its homeostasis throughout adulthood. A complex balance between cell death- and survival-inducing signals determines the fate of individual neurons. Intracellular cAMP is thought to regulate neuronal survival, and previous studies have shown that the survival of retinal ganglion cells by brain-derived neurotrophic factor (BDNF) is dependent on cAMP. Here we report the surprising observation that cAMP attenuates the ability of BDNF to rescue cortical neurons from apoptosis after serum deprivation, a process mediated via the phosphatidylinositol 3 (PI3)-kinase signal transduction cascade. Depolarization by KCl, which increases cAMP in cortical neurons, also attenuates BDNF protection against serum withdrawal. Our data indicate that cAMP antagonizes neurotrophin protection from serum withdrawal by inhibiting the PI3-kinase signal transduction cascade. This study indicates that cAMP may inhibit some forms of neurotrophin-mediated neuronal survival and suggests that a number of PI3-kinase-regulated processes in neurons may be inhibited by cAMP. FAU - Poser, Steven AU - Poser S AD - Department of Pharmacology, University of Washington, Seattle, Washington 98195-7280, USA. FAU - Impey, Soren AU - Impey S FAU - Xia, Zhengui AU - Xia Z FAU - Storm, Daniel R AU - Storm DR LA - eng GR - R01 DC004158/DC/NIDCD NIH HHS/United States GR - R01 NS020498/NS/NINDS NIH HHS/United States GR - DC 04158/DC/NIDCD NIH HHS/United States GR - NS 20498/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Blood Proteins) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Neuroprotective Agents) RN - 660YQ98I10 (Potassium Chloride) RN - E0399OZS9N (Cyclic AMP) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Blood Proteins/pharmacology MH - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/*pharmacology MH - Cell Survival/drug effects MH - Cells, Cultured MH - Cerebral Cortex/cytology MH - Cyclic AMP/metabolism/*pharmacology MH - Cyclic AMP-Dependent Protein Kinases/metabolism MH - Mitogen-Activated Protein Kinases/metabolism MH - Neurons/cytology/*drug effects/metabolism MH - Neuroprotective Agents/antagonists & inhibitors/*pharmacology MH - Phosphatidylinositol 3-Kinases/metabolism MH - Potassium Chloride/pharmacology MH - Rats MH - Signal Transduction/drug effects MH - Transfection PMC - PMC6740814 EDAT- 2003/06/14 05:00 MHDA- 2003/07/02 05:00 PMCR- 2003/12/01 CRDT- 2003/06/14 05:00 PHST- 2003/06/14 05:00 [pubmed] PHST- 2003/07/02 05:00 [medline] PHST- 2003/06/14 05:00 [entrez] PHST- 2003/12/01 00:00 [pmc-release] AID - 23/11/4420 [pii] AID - 10.1523/JNEUROSCI.23-11-04420.2003 [doi] PST - ppublish SO - J Neurosci. 2003 Jun 1;23(11):4420-7. doi: 10.1523/JNEUROSCI.23-11-04420.2003.