Nebracetam Inhibited Hippocampus Neurons Injury Induced by AÃÂ²25-35 in MRTF-A-CArG Manner via ERK1/2 PathwayTingzi Yin, Xiaolu Cao, Wan Xiao, Ying Zhang, Shuqi Zhao and Xiamin Hu*
Department of Pharmacology, Medical College of Wuhan University of Science and Technology, Huangjiahu Road Wuhan, PR China 430065
- *Corresponding Author:
- Xiamin Hu
Department of Pharmacology, Medical College of Wuhan
University of Science and Technology, Wuhan, PR China
E-mail: [email protected]
Received date: December 30, 2015; Accepted date: January 02, 2016; Published date: January 11, 2016
Citation: Yin T, Cao X, Xiao W, Zhang Y, Zhao S, et al. (2016) Nebracetam Inhibited Hippocampus Neurons Injury Induced by Aß25-35 in MRTF-A-CArG Manner via ERK1/2 Pathway. Mol Biol 5:152. doi: 10.4172/2168-9547.1000152
Copyright: © 2016 Yin T, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Nebracetam has been recently proposed to have a neuroprotective action and cognitive enhancing effect being characteristic of a nootropic drug, while the mechanisms remained ambiguity. In this study, we investigated the protective effects of nebracetam on hippocampus neurons injury-induced by β-amyloid protein(Aβ25-35)and its mechanisms. Hippocampus neurons were treated with nebracetam (0.05 mM, 0.2 mM or 0.8 mM) or Aβ25-35 (20 uM/L). We found that Nebracetam significantly reduced apoptotic induced by Aβ25-35 and increase in the total number of dendritic spines and dendritic spine density in a dose-dependent manner. RT-PCR assay and Western blotting analysis revealed that nebracetam increased the expressions of myeloid cell leukemia-1 (Mcl-1), B-cell lymphoma-2 (Bcl-2) and activity regulated cytoskeleton associated protein (Arc) in Aβ25-35-treated hippocampus neurons. Cotreatment nebracetam with MRTF-A (Myocardin-related transcription factor-A) siRNA reversed Mcl-1, Bcl-2 and Arc mRNA and protein levels. What’s more, the luciferase assays indicated that the transcriptional activities of Mcl-1, Bcl-2 and Arc genes were significantly abolished by MRTF-A siRNA while it showed no changes on activities of mut Mcl- 1-promoter-luc, mut Bcl-2-promoter-luc and mut Arc-promoter-luc. Additionally, the up-regulation of Mcl-1, Bcl-2 and Arc protein expressions in nebracetam-treated group was inhibited by extracellular signal regulated protein kinase 1/2 (ERK1/2) inhibitor PH98059. These results demonstrated that nebracetam inhibited Aβ25-35-induced hippocampus neurons injury by enhancing the transactivity of Mcl-1, Bcl-2 and Arc, which may actively based in MRTF-A-CArGdependent manner by thwarting the ERK1/2 pathway.