Objective: We investigated expression of eEF1A2 and Prdx1 in differentiated SH-SY5Y cells in searching for possible new targets for Parkinson’s disease treatment.

Background: Parkinson’s disease (PD) is a progressive disorder of the nervous system. Development of disease-modifying drugs has been a remarkable advancement in recent years, based on proteins involved in the pathogenesis. Eukaryotic translation elongation factor 1 alpha 2 (eEF1A2) is one of the two isoforms of elongation factor eEF1A. eEF1A2 has a very restricted pattern of expression and they are found in neurons, cardiomyocytes and myotubes, while eEF1A1 extensively expresses. A previous study showed that exposure of SH-SY5Y cells to MPP+ significantly increased the expression of eEF1A2 in accordance with the PI3K/Akt/mTOR signaling proteins. Moreover, the investigation in yeast two-hybrid system showed eEF1A2 interacts with peroxiredoxin type 1 (Prdx1) but not with eEF1A1 to defense stress conditions. Prdx1 is a typical 2-Cys peroxiredoxin, ubiquitously expressed in all mammalian cells, and plays role in cell protection by reducing reactive oxygen species. Its expression in mouse dopaminergic neurons of the substantia nigra is very low, suggesting that Prdx1 may affect neuronal sensitivity to oxidative stress and may contribute to the development of PD.

Methods: We induced SH-SY5Y cells differentiation with 10 µM retinoic acid for 3, 5, 7 and 10 days. Tyrosine hydroxyl expression was measured by Western blotting to ensure the dopaminergic phenotype. Gene and protein expression of eEF1A2 and Prdx1 were investigated by real time PCR and western blot analysis, respectively. The localizations of eEF1A2 and Prdx1 were visualized by immunofluorescence.

Results: The real time PCR and western blot analysis showed that differentiated cells had a significant increase of eEF1A2 mRNA and protein expression (p<0.05), compared to undifferentiated cells. Conversely, Prdx1 protein was progressively decreased during differentiation. These results were consistent with the immunofluorescent study.

Conclusions: eEF1A2 and Prdx1 have a reverse expression during neuronal differentiation. Further investigation on manipulation of these two protein expression in cellular and animal models of PD may shed light for development of PD therapeutic strategies.

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. Goemaere J, Knoops B. Peroxiredoxin distribution in the mouse brain with emphasis on neuronal populations affected in neurodegenerative disorders. J Comp Neurol. 2012 Feb 1;520(2):258-80.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/eef1a2-and-prdx1-as-possible-new-targets-for-parkinsons-disease-therapeutics/