title: Methyl 3,4-dihydroxybenzoate promote rat cortical neurons survival and neurite outgrowth through the adenosine A2a receptor/PI3K/Akt signaling pathway.
abstract: Methyl 3,4-dihydroxybenzoate (MDHB), a kind of phenolic acid compounds, has been reported to have antioxidant effects. Moreover, our previous study found that it could promote neurite outgrowth and brain-derived neurotrophic factor expression in cortical neurons of neonatal rats. In the present study, we focused on the mechanism of its neurotrophic effect; the results showed that MDHB-induced upregulation of neuronal survival and neurite outgrowth in cultured primary cortical neurons could be blocked by the adenosine A2a receptor inhibitor (ZM241385) and the phosphoinositide 3-kinase (PI3K) inhibitor (LY294002). Subsequently, we found that the upregulation of Akt phosphorylation by MDHB could be suppressed by A2a-R and PI3K-specific inhibitor, but not the Trk-R inhibitor. Furthermore, MDHB could activate Akt in a concentration-dependent manner. These results suggested that activation of the PI3K/Akt signaling pathway may be involved in the MDHB-induced neurotrophic effects and MDHB could be a candidate compound to develop drugs for neurodegenerative disease.
authors: aDepartment of Pharmacy, The First Affiliated Hospital of Jinan University bDepartment of Pharmacology, School of Medicine, Jinan University cPharmacy Department of Guangzhou Chest Hospital dInstitute of Brain Sciences, Jinan University, Guangzhou, China.
authors: Zheng
authors: Z
authors: Zhang
authors: Liang
authors: L
authors: Cai
authors: Xiaowen
authors: X
authors: Zhou
authors: Chaofen
authors: C
authors: Su
authors: Fei
authors: F
authors: Xiao
authors: Qin
authors: Q
authors: Gao
authors: Huanmin
authors: H
authors: Luo
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D062385:Hydroxybenzoates / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D062385:Hydroxybenzoates; D043705:Receptor, Adenosine A2A; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C000600341:methyl 3,4-dihydroxybenzoate