Inhibition of the antioxidant enzyme PRDX1 activity promotes MPP+-induced death in differentiated SH-SY5Y cells and may impair its colocalization with eEF1A2

Wirakiat, Wimon; Prommahom, Athinan; Dharmasaroja, Permphan

doi:10.1016/j.lfs.2020.118227

Cited by 11 publications

(6 citation statements)

References 44 publications

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“…Our results showed an increase in pyramidal-shaped cell bodies and the extension of neurite processes of retinoic acid-treated SH-SY5Y cells, together with increased fluorescence intensity of TH, suggesting differentiation of the cells into neuronal cells. This neuronal differentiation was associated with an increase in the eEF1A2 protein, as shown in the fluorescent staining, which is similar to our previous observations on the protein blotting [ 20 , 25 , 26 ]. eEF1A2 is highly expressed in postmitotic cells, and studies showed that eEF1A2 might be required for neuronal differentiation of SH-SY5Y cells [ 26 ].…”

Section: Discussionsupporting

confidence: 90%

eEF1A2 siRNA Suppresses MPP+-Induced Activation of Akt and mTOR and Potentiates Caspase-3 Activation in a Parkinson’s Disease Model

Khwanraj

Prommahom

Dharmasaroja

2023

The Scientific World Journal

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The tissue-specific protein eEF1A2 has been linked to the development of neurological disorders. The role of eEF1A2 in the pathogenesis of Parkinson’s disease (PD) has yet to be investigated. The aim of this study was to determine the potential neuroprotective effects of eEF1A2 in an MPP+ model of PD. Differentiated SH-SY5Y cells were transfected with eEF1A2 siRNA, followed by MPP+ exposure. The expression of p-Akt1 and p-mTORC1 was determined using Western blotting. The expression of p53, Bax, Bcl-2, and caspase-3 was evaluated using qRT-PCR. Cleaved caspase-3 levels and Annexin V/propidium iodide flow cytometry were used to determine apoptosis. The effects of PI3K inhibition were examined. The results showed that eEF1A2 siRNA significantly reduced the eEF1A2 expression induced by MPP+. MPP+ treatment activated Akt1 and mTORC1; however, eEF1A2 knockdown suppressed this activation. In eEF1A2-knockdown cells, MPP+ treatment increased the expression of p53 and caspase-3 mRNA levels as well as increased apoptotic cell death when compared to MPP+ treatment alone. In cells exposed to MPP+, upstream inhibition of the Akt/mTOR pathway, by either LY294002 or wortmannin, inhibited the phosphorylation of Akt1 and mTORC1. Both PI3K inhibitors increased eEF1A2 expression in cells, whether or not they were also treated with MPP+. In conclusion, eEF1A2 may function as a neuroprotective factor against MPP+, in part by regulating the Akt/mTOR pathway upstream.

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Section: Discussionsupporting

confidence: 90%

eEF1A2 siRNA Suppresses MPP+-Induced Activation of Akt and mTOR and Potentiates Caspase-3 Activation in a Parkinson’s Disease Model

Khwanraj

Prommahom

Dharmasaroja

2023

The Scientific World Journal

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“…Alternatively, our results showed that neuronal viability was increased while LDH release and neuronal apoptosis were decreased in OGD-treated neurons after EEF1A2 overexpression. EEF1A2 is associated with suppressed apoptosis [ 35 ]. Specifically, EEF1A2 overexpression promoted viability and inhibited apoptosis of spinal cord neurons.…”

Section: Discussionmentioning

confidence: 99%

METTL14 promotes apoptosis of spinal cord neurons by inducing EEF1A2 m6A methylation in spinal cord injury

et al. 2022

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Spinal cord injury (SCI) is a devastating traumatic condition. METTL14-mediated m6A modification is associated with SCI. This study was intended to investigate the functional mechanism of RNA methyltransferase METTL14 in spinal cord neuron apoptosis during SCI. The SCI rat model was established, followed by evaluation of pathological conditions, apoptosis, and viability of spinal cord neurons. The neuronal function of primary cultured spinal motoneurons of rats was assessed after hypoxia/reoxygenation treatment. Expressions of EEF1A2, Akt/mTOR pathway-related proteins, inflammatory cytokines, and apoptosis-related proteins were detected. EEF1A2 was weakly expressed and Akt/mTOR pathway was inhibited in SCI rat models. Hypoxia/Reoxygenation decreased the viability of spinal cord neurons, promoted LDH release and neuronal apoptosis. EEF1A2 overexpression promoted the viability of spinal cord neurons, inhibited neuronal apoptosis, and decreased inflammatory cytokine levels. Silencing METTL14 inhibited m6A modification of EEF1A2 and increased EEF1A2 expression while METTL14 overexpression showed reverse results. EEF1A2 overexpression promoted viability and inhibited apoptosis of spinal cord neurons and inflammation by activating the Akt/mTOR pathway. In conclusion, silencing METTL14 repressed apoptosis of spinal cord neurons and attenuated SCI by inhibiting m6A modification of EEF1A2 and activating the Akt/mTOR pathway.

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“…PRDX1 is a critical peroxidase enzyme that plays dominant roles in regulating ROS levels and downstream signaling pathways within cells (32). PRDX1 is involved in the pathology of various age-related diseases and cancers, including AD and Parkinson's disease (33). In the present study, it was shown that DHA but not lutein could up-regulate the expression of PRDX1 mRNA in PC12 cell.…”

Section: Discussionmentioning

confidence: 45%

Combination of Lutein and DHA Alleviate H<sub>2</sub>O<sub>2</sub> Induced Cytotoxicity in PC12 Cells by Regulating the MAPK Pathway

Zhang

Lian

et al. 2021

J Nutr Sci Vitaminol

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Docosahexaenoic acid (DHA) and lutein are important nutrients for brain health. Whether there were synergistic effects of DHA and lutein on the protection against neuronal cell damage induced by oxidative stress remained unclear. The present study was designed to investigate the synergistic effects of DHA and lutein against hydrogen peroxide (H2O2)-induced oxidative challenge in PC12 cells. PC12 cells were divided into different groups and received H2O2 (80 mM), lutein (20 mM)1H2O2 (80 mM), DHA (25 mM)1H2O2 (80 mM), and lutein (20 mM)1DHA (25 mM)1H2O2 (80 mM), respectively. The results indicated that pre-treatment of cells with lutein, DHA and DHA1lutein could significantly antagonize the H2O2-mediated growth inhibition and morphological changes in PC12 cells (p,0.05). Molecular-level studies indicated that the DHA1lutein combination can significantly inhibit the mRNA expression of AMAD10 and BAX. Furthermore, Western blot analysis demonstrated that DHA1lutein synergistically inhibits the phosphorylation of JNK1/2. The results of the present study suggest that DHA and lutein in combination may be utilized as potent anti-oxidative compounds, with potential preventative or palliative effects on age-related neurodegenerative diseases.

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Inhibition of the antioxidant enzyme PRDX1 activity promotes MPP+-induced death in differentiated SH-SY5Y cells and may impair its colocalization with eEF1A2

Cited by 11 publications

References 44 publications

eEF1A2 siRNA Suppresses MPP+-Induced Activation of Akt and mTOR and Potentiates Caspase-3 Activation in a Parkinson’s Disease Model

eEF1A2 siRNA Suppresses MPP+-Induced Activation of Akt and mTOR and Potentiates Caspase-3 Activation in a Parkinson’s Disease Model

METTL14 promotes apoptosis of spinal cord neurons by inducing EEF1A2 m6A methylation in spinal cord injury

Combination of Lutein and DHA Alleviate H<sub>2</sub>O<sub>2</sub> Induced Cytotoxicity in PC12 Cells by Regulating the MAPK Pathway

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