title: Curcumin Protects Neurons from Glutamate-Induced Excitotoxicity by Membrane Anchored AKAP79-PKA Interaction Network.
abstract: Now stimulation of AMPA receptor as well as its downstream pathways is considered as potential central mediators in antidepressant mechanisms. As a signal integrator which binds to AMPA receptor, A-kinase anchoring protein 79-(AKAP79-) PKA complex is regarded as a potential drug target to exert neuroprotective effects. A well-tolerated and multitarget drug curcumin has been confirmed to exert antidepressant-like effects. To explore whether AKAP79-PKA complex is involved in curcumin-mediated antiexcitotoxicity, we detected calcium signaling, subcellular location of AKAP79-PKA complex, phosphorylation of glutamate receptor, and ERK and AKT cascades. In this study, we found that curcumin protected neurons from glutamate insult by reducing Ca(2+) influx and blocking the translocation of AKAP79 from cytomembrane to cytoplasm. In parallel, curcumin enhanced the phosphorylation of AMPA receptor and its downstream pathways in PKA-dependent manner. If we pretreated cells with PKA anchoring inhibitor Ht31 to disassociate PKA from AKAP79, no neuroprotective effects were observed. In conclusion, our results show that AKAP79-anchored PKA facilitated the signal relay from AMPA receptor to AKT and ERK cascades, which may be crucial for curcumin-mediated antiexcitotoxicity.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China ; Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China ; Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: An
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China ; Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Tie
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China ; Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China ; Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Li