Effects of eEF1A2 knockdown on autophagy in an MPP+-induced cellular model of Parkinson's disease.

Athinan Prommahom, Permphan Dharmasaroja

Neuroscience research 2021 Mar

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1-Methyl-4-phenylpyridinium ion (MPP+) is widely used to induce a cellular model of Parkinson's disease (PD) in dopaminergic cell lines. Downregulation of the protein translation elongation factor 1 alpha (eEF1A) has been reported in the brain tissue of PD patients. eEF1A2, an isoform of eEF1A, is associated with lysosome biogenesis that involves the autophagy process. However, the role of eEF1A2 on autophagic activity in PD has not been elucidated. In this work, we investigated the role of eEF1A2 on autophagy using eEF1A2 siRNA knockdown in differentiated SH-SY5Y neuronal cells treated with MPP+. We found that eEF1A2 was upregulated in differentiated cells, which could be silenced by eEF1A2 siRNA. Significantly, cells treated with MPP+ after eEF1A2 knockdown showed a decreased number of LC3 puncta, decreased LC3-II/LC3-I ratio, and decreased phospho-Beclin-1, compared to the MPP+ alone group. These cells showed extensive areas of mitochondria damage, with a reduction of mitochondrial membrane potential, but reduced mitophagy as indicated by the reduced colocalization of LC3 puncta with damaged mitochondria. Cells with eEF1A2 siRNA plus MPP+ treatment aggravated α-synuclein accumulation but reduced colocalization with LC3. As a result, eEF1A2 knockdown decreased viability, increased apoptotic nuclei, increased caspase-3/7 activation and increased cleaved caspase-3 when cells were treated with MPP+. These results suggest that eEF1A2 is essential for dopaminergic neuron survival against MPP+, in part through autophagy regulation. Copyright © 2020 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

Citation

Athinan Prommahom, Permphan Dharmasaroja. Effects of eEF1A2 knockdown on autophagy in an MPP+-induced cellular model of Parkinson's disease. Neuroscience research. 2021 Mar;164:55-69