Brain Res Mol Brain Res 2003,
PMID: 14625085
Yamagishi, Satoru; Matsumoto, Tomoya; Yokomaku, Daisaku; Hatanaka, Hiroshi; Shimoke, Koji; Yamada, Masashi; Ikeuchi, Toshihiko
On cell maturation following culture in medium containing 26 mM potassium (high K+; HK), a change to medium containing 5 mM potassium (low K+; LK) rapidly induces apoptosis in rat cerebellar granule neurons. Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) have survival-promoting effects on the neurons via PI3-K. However, it remains unclear how they prevent the apoptosis in the pathway downstream of phosphatidylinositol-3 kinase (PI3-K). Recently, we have reported that PI3-K-ASK1 pathway is involved in signal-transduction to p38 MAPK (p38)-c-Jun pathway. Here we found that IGF-1 had a greater survival-promoting effect than BDNF, and activated PI3-K to a higher level and maintained the level for a longer time. BDNF and IGF-1 suppressed the activation of p38 and c-Jun, but not of c-Jun N-terminal kinase (JNK), caused by lowering the potassium concentration. The inhibitory effects of IGF-1 were much greater than those of BDNF. In addition, LY294002, a specific inhibitor of PI3-K, cancelled the inhibitory effects of BDNF and IGF-1. These results suggest that the greater inhibitory effects of IGF-1 than BDNF, on activation of p38 and c-Jun and apoptosis, are caused by the higher level of PI3-K activation during LK-induced apoptosis of cultured cerebellar granule neurons.
Diseases/Pathways annotated by Medline MESH: Potassium Deficiency
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Text Mining Data
MAPK — brain derived neurotrophic factor: "
Comparison of inhibitory
effects of
brain derived neurotrophic factor and insulin-like growth factor on low potassium induced apoptosis and activation of p38
MAPK and c-Jun in cultured cerebellar granule neurons
"
MAPK — insulin-like growth factor: "
Comparison of inhibitory effects of brain derived neurotrophic factor and insulin-like growth factor on low potassium induced apoptosis and activation of p38 MAPK and c-Jun in cultured cerebellar granule neurons
"
c-Jun — brain derived neurotrophic factor: "
Comparison of inhibitory effects of brain derived neurotrophic factor and insulin-like growth factor on low potassium induced apoptosis and activation of p38 MAPK and c-Jun in cultured cerebellar granule neurons
"
c-Jun — insulin-like growth factor: "
Comparison of inhibitory effects of brain derived neurotrophic factor and insulin-like growth factor on low potassium induced apoptosis and activation of p38 MAPK and c-Jun in cultured cerebellar granule neurons
"
PI3-K → IGF-1: "
Here we found that IGF-1 had a greater survival promoting effect than BDNF, and activated PI3-K to a higher level and maintained the level for a longer time
"
p38 ⊣ BDNF: "
BDNF and IGF-1 suppressed the activation of p38 and c-Jun, but not of c-Jun N-terminal kinase (JNK), caused by lowering the potassium concentration
"
p38 ⊣ IGF-1: "
BDNF and IGF-1 suppressed the activation of p38 and c-Jun, but not of c-Jun N-terminal kinase (JNK), caused by lowering the potassium concentration
"
c-Jun ⊣ BDNF: "
BDNF and IGF-1 suppressed the activation of p38 and c-Jun , but not of c-Jun N-terminal kinase (JNK), caused by lowering the potassium concentration
"
c-Jun N-terminal kinase (JNK) ⊣ IGF-1: "
BDNF and IGF-1 suppressed the activation of p38 and c-Jun, but not of c-Jun N-terminal kinase (JNK) , caused by lowering the potassium concentration
"
Manually curated Databases
No curated data.