Phosphorylation of Akt is involved in protocatechuic acid-induced neurotrophic activity.
OBJECTIVE
To investigate the mechanisms underlying protocatechuic acid (PCA)-induced neurotrophic effects on cultured cortical neurons.


METHODS
The mRNA expression of microtubule-associated protein 2 (MAP2) and brain-derived neurotrophic factor (BDNF) were measured  by real-time quantitative PCR (qPCR). Subsequently, antagonists were used to study the signaling pathways activated by PCA and western blotting was used to detect the phosphorylation level of kinase-related protein.


RESULTS
The mRNA expression of MAP2 and BDNF were upregulated in  neurons treated with PCA compared with vehicle control. PCA-induced neurite outgrowth and neuronal survival in cultured cortical neurons were significantly inhibited by ZM241385 (an A(2A) receptor antagonist) and LY294002 (a PI3K inhibitor), but not by K252a (a TrkA receptor antagonist),  GÖ6976 (a protein kinase C inhibitor) and PD98059 (a MEK inhibitor). PCA enhanced the phosphorylation of Akt, which could be blocked by LY294002.


CONCLUSIONS
The PI3K/Akt signaling pathway might play an important role in the neurotrophic activity of PCA.
Ganzhou People's Hospital, Ganzhou, China.
Xiao-Yan
XY
Xue
Min-Jing
MJ
Liao
Lian-Feng
LF
Lin
Zheng
Z
Zhang
Xiao-Wen
XW
Zhou
Xing
X
Zhou
Huan-Min
HM
Luo
D000818:Animals; D000831:Animals, Newborn; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D062385:Hydroxybenzoates / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009474:Neurons / Q000187:drug effects*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
D016588:Anticarcinogenic Agents; D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D062385:Hydroxybenzoates; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; C009091:protocatechuic acid; D051058:Oncogene Protein v-akt