Phosphorylation of Akt is involved in protocatechuic acid-induced neurotrophic activity

AbstractObjective: 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 A2A receptor antagonist) and LY294002 (a PI3K inhibitor), but not by K252a (a TrkA receptor antagonist), GO6976 (a protein kinase C inhibitor) and PD98059 (a MEK inhibitor). PCA enhanced the phosphorylation of Akt, which could be blocked by LY294002.Conclusion: The PI3K/Akt signali...