Session Information
Date: Wednesday, June 7, 2017
Session Title: Parkinson's Disease: Genetics
Session Time: 1:15pm-2:45pm
Location: Exhibit Hall C
Objective: To assess the correlation of eEF1A2 and PI3K/Akt/mTOR expression and investigate the pro-survival role of eEF1A2 in NG108-15 rodent neuroglioma cells.
Background: Eukaryotic protein elongation factor 1 alpha 2 (eEF1A2) is one of the members of the eEF1A family, which plays a canonical role in protein synthesis during the elongation phase of protein translation. A non-canonical role in pro-survival has been shown in many cancers and neurodegenerative diseases. An increase of eEF1A2 expression causes cancer progression whereas a decrease of eEF1A2 has been linked to neuronal death in many neurodegenerative diseases. eEF1A2 is proposed to contribute protection against apoptotic cell death, likely through activation of the PI3K/Akt pathway. Akt is activated by various toxins and involved in cell survival and proliferation as well as exerting an anti-apoptotic effect. Previous evidence has also shown correlated expression of eEF1A2 with the PI3K/Akt/mTOR pathway in a cellular model of Parkinson’s disease.
Methods: We studied the expression of eEF1A2 in both undifferentiated and differentiated NG108-15 after treatment with the neuronal toxin MPP+. To study the pro-survival role of eEF1A2 we also checked the expression of PI3K/Akt/mTOR both before and after RNAi knockdown of eEF1A2 by using quantitative real time PCR and western blot analysis.
Results: There was a trend towards an increase of the expression of eEF1A2 after treatment with MPP+ in both undifferentiated and differentiated cells, when compared with control. Meanwhile, the expression of PI3K/Akt/mTOR proteins were increased in both differentiated and undifferentiated NG108-15 cells treated with MPP+, especially for the phosphorylated Akt protein. After eFE1A2 knockdown, the expression of PI3K/Akt/mTOR was significantly increased, but the ratio of p-Akt/total Akt was lesser than that of non eEF1A2 knockdown.
Conclusions: The present findings suggested that eEF1A2 may promote survival of NG108-15 cells through the PI3K/Akt/mTOR pathway by the enhanced expression of phosphorylated Akt in order to protect MPP+ neurotoxin induced cell death. Further investigation is required to confirm our findings, such as the expression of apoptosis and oxidative stress markers.
References:
- Khwanraj K, Madlah S, Grataitong K, Dharmasaroja P. Comparative mRNA Expression of eEF1A Isoforms and a PI3K/Akt/mTOR Pathway in a Cellular Model of Parkinson’s Disease. Parkinsons Dis. 2016; 2016: 8716016.
- Kamarudin MN, Mohd Raflee NA, Hussein SS, Lo JY, Supriady H, Abdul Kadir H. (R)-(+)-α-Lipoic acid protected NG108-15 cells against H2O2-induced cell death through PI3K-Akt/GSK-3β pathway and suppression of NF-κβ-cytokines. Drug Des Devel Ther. 2014; 8:1765-1780.
To cite this abstract in AMA style:
K. Khwanraj, P. Dharmasaroja, B. Morris. eEF1A2 promotes cell survival and protects against MPP+-induced apoptotic neuronal death through the PI3K/Akt/mTOR pathway [abstract]. Mov Disord. 2017; 32 (suppl 2). https://www.mdsabstracts.org/abstract/eef1a2-promotes-cell-survival-and-protects-against-mpp-induced-apoptotic-neuronal-death-through-the-pi3kaktmtor-pathway/. Accessed May 13, 2025.« Back to 2017 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/eef1a2-promotes-cell-survival-and-protects-against-mpp-induced-apoptotic-neuronal-death-through-the-pi3kaktmtor-pathway/