Neuroprotection of brain-derived neurotrophic factor against hypoxic injury in vitro requires activation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase.
Intrauterine asphyxia is one of the major contributors for perinatal death, mental and physical disorders of surviving children. Brain-derived neurotrophic factor (BDNF) provides a promising solution to hypoxic injury due to its survival-promoting effects. In an attempt to identify possible molecular mechanisms underlying the neuroprotective role of BDNF, we studied extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI-3-K) and p38 mitogen-activated protein kinase (MAPK) pathways. We demonstrated that BDNF protected cortical neurons against hypoxic injury in vitro via activation of both the ERK and PI-3-K pathways but not the p38 MAPK pathway. We also showed that both hypoxic stimuli and exogenous BDNF treatment phosphorylated the cyclic AMP response element-binding protein (CREB) and that CREB phosphorylation induced by BDNF was mediated via the ERK pathway in cultured cortical neurons.
Sun
Xiaomei
X
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, PR China.
Zhou
Hui
H
Luo
Xiaoli
X
Li
Shengfu
S
Yu
Dan
D
Hua
Jiping
J
Mu
Dezhi
D
Mao
Meng
M
D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005311:Fetal Hypoxia / Q000201:enzymology* / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D051381:Rats
D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D048052:Mitogen-Activated Protein Kinase 3