Phosphorylation of cAMP response element-binding protein in hippocampal neurons as a protective response after exposure to glutamate in vitro and ischemia in vivo

被引:238
作者
Mabuchi, T
Kitagawa, K
Kuwabara, K
Takasawa, K
Ohtsuki, T
Xia, ZG
Storm, D
Yanagihara, T
Hori, M
Matsumoto, M
机构
[1] Osaka Univ, Grad Sch Med, Dept Internal Med & Therapeut A8, Div Strokol, Suita, Osaka 5650871, Japan
[2] Osaka Univ, Grad Sch Med, Dept Clin Neurosci, Suita, Osaka 5650871, Japan
[3] Univ Washington, Dept Environm Hlth, Seattle, WA 98195 USA
[4] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA
关键词
CREB; ischemia; BCL-2; beta-galactosidase; glutamate; CRE-decoy oligonucleotide;
D O I
10.1523/JNEUROSCI.21-23-09204.2001
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Although accumulating evidence indicates that cAMP response element-binding protein (CREB) phosphorylation mediates not only synaptic plasticity but also survival of certain neurons, it remains uncertain whether CREB phosphorylation induced after metabolic insult leads to CRE-mediated gene transcription and is involved in cell survival or not. In the present study, we clarified that (1) CREB phosphorylation and ischemic tolerance induced after preconditioning ischemia in the hippocampal neurons was abolished by MK801 administration in gerbil global ischemia model, (2) CREB phosphorylation induced after exposure to glutamate in cultured neurons was inhibited by removal of extracellular calcium, by MK801 and by an inhibitor of calcium-calmodulin-dependent protein kinase (CaMK) II and IV, (3) inhibitor of CaMK II-IV or CRE-decoy oligonucleotide suppressed upregulation of BCL-2 expression and accelerated neuronal damage after exposure to glutamate, and (4) CREB phosphorylation induced in the hippocampal neurons after ischemia and in cultured neurons after exposure to glutamate was followed by CRE-mediated gene transcription in transgenic mice with a CRE-LacZ reporter. Our results suggest that CREB phosphorylation in neurons after ischemia and exposure to glutamate is induced by NMDA receptor-gated calcium influx and subsequent activation of CaMK II-IV and that CREB phosphorylation after metabolic stress might show a neuroprotective response through CRE-mediated gene induction.
引用
收藏
页码:9204 / 9213
页数:10
相关论文
共 43 条
[31]   Developmentally regulated NMDA receptor-dependent dephosphorylation of cAMP response element-binding protein (CREB) in hippocampal neurons [J].
Sala, C ;
Rudolph-Correia, S ;
Sheng, M .
JOURNAL OF NEUROSCIENCE, 2000, 20 (10) :3529-3536
[32]  
Schulz S, 1999, J NEUROSCI, V19, P5683
[33]   Calcium/calmodulin-dependent protein kinase type IV (CaMKIV) inhibits apoptosis induced by potassium deprivation in cerebellar granule neurons [J].
Sée, V ;
Boutiller, AL ;
Bito, H ;
Loeffler, JP .
FASEB JOURNAL, 2001, 15 (01) :134-144
[34]  
Sgambato V, 1998, J NEUROSCI, V18, P8814
[35]   MEMBRANE DEPOLARIZATION AND CALCIUM INDUCE C-FOS TRANSCRIPTION VIA PHOSPHORYLATION OF TRANSCRIPTION FACTOR CREB [J].
SHENG, M ;
MCFADDEN, G ;
GREENBERG, ME .
NEURON, 1990, 4 (04) :571-582
[36]   Identification of a signaling pathway involved in calcium regulation of BDNF expression [J].
Shieh, PB ;
Hu, SC ;
Bobb, K ;
Timmusk, T ;
Ghosh, A .
NEURON, 1998, 20 (04) :727-740
[37]   Temporal profile of CREB phosphorylation after focal ischemia in rat brain [J].
Tanaka, K ;
Nogawa, S ;
Nagata, E ;
Suzuki, S ;
Dembo, T ;
Kosakai, A ;
Fukuuchi, Y .
NEUROREPORT, 1999, 10 (11) :2245-2250
[38]  
Vanhoutte P, 1999, MOL CELL BIOL, V19, P136
[39]  
Walton M, 1999, J NEUROCHEM, V73, P1836
[40]   The role of the cyclic AMP-responsive element binding protein (CREB) in hypoxic-ischemic brain damage and repair [J].
Walton, M ;
Sirimanne, E ;
Williams, C ;
Gluckman, P ;
Dragunow, M .
MOLECULAR BRAIN RESEARCH, 1996, 43 (1-2) :21-29