Abstract
6-Hydroxydopamine (6-OHDA), a metabolite of dopamine is known to induce dopaminergic cell toxicity which makes that a suitable agent inducing an experimental model of Parkinson’s disease (PD). Agmatine has been shown to protect against some cellular and animal PD models. This study was aimed to assess whether agmatine prevents 6-OHDA-induced SH-SY5Y cell death and if yes, then how it affects Akt/glycogen synthesis kinase-3β (GSK-3β) and extracellular signal-regulated kinases (ERK) signals. The cells were treated with different drugs, and their viability was examined via MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay and morphological observation. Western blot studies were done to assess cleaved caspase-3, Akt/GSK-3β, and ERK proteins. 6-OHDA-induced cell death and caspase-3 cleavage, while agmatine prevented those changes. 6-OHDA also decreased the amount of phosphorylated Akt (pAkt)/Akt while increased GSK-3β activity which was prevented by agmatine. Additionally, this toxin increased pERK/ERK ratio which was averted again by agmatine. The PI3/Akt inhibitor, LY294002, impeded the changes induced by agmatine, while ERK inhibitor (PD98059) did not disturb the effects of agmatine, and by itself, it preserved the cells against 6-OHDA toxicity. This study revealed that agmatine is protective in 6-OHDA model of PD and affects Akt/GSK-3β and ERK pathways.
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Change history
26 July 2018
The original version of this article unfortunately contained a mistake in the unit of agmatine doses. The agmatine doses were erroneously written in nanomolar in the published article. The correct effective doses of agmatine were 150 and 250 µM.
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Acknowledgments
This work was derived from the thesis of Esmat Amiri and supported by a Grant (No. 92-6735) from Shiraz University of Medical Sciences, Shiraz, Iran. The authors would like to appreciate Ms. Mehrnaz Gholami for her help in editing the manuscript.
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Amiri, E., Ghasemi, R. & Moosavi, M. Agmatine Protects Against 6-OHDA-Induced Apoptosis, and ERK and Akt/GSK Disruption in SH-SY5Y Cells. Cell Mol Neurobiol 36, 829–838 (2016). https://doi.org/10.1007/s10571-015-0266-7
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DOI: https://doi.org/10.1007/s10571-015-0266-7