Dual Specificity Phosphatase 6 Protects Neural Stem Cells from β-Amyloid-Induced Cytotoxicity through ERK1/2 Inactivation
AbstractAlzheimer’s disease (AD) is a devastating neurodegenerative disease with limited treatment options and no cure. Beta-amyloid (Aβ) is a hallmark of AD that has potent neurotoxicity in neural stem cells (NSCs). Dual specificity phosphatase 6 (DUSP6) is a member of the mitogen-activated protein kinases (MAPKs), which is involved in regulating various physiological and pathological processes. Whether DUSP6 has a protective effect on Aβ-induced NSC injury remains to be explored. C17.2 neural stem cells were transfected with DUSP6-overexpressed plasmid. NSCs with or without DUSP6 overexpression were administrated with Aβ25–35 at various concentrations (i.e., 0, 2.5, 5 μM). DUSP6 expression after Aβ treatment was detected by Real-Time Polymerase Chain Reaction (RT-PCR) and Western blot and cell vitality was examined by the CCK8 assay. The oxidative stress (intracellular reactive oxygen species (ROS) and malondialdehyde (MDA)), endoplasmic reticulum stress (ER calcium level) and mitochondrial dysfunction (cytochrome c homeostasis) were tested. The expression of p-ERK1/2 and ERK1/2 were assayed by Western blot. Our results showed that Aβ decreased the expression of DUSP6 in a dose-dependent manner. The overexpression of DUSP6 increased the cell vitality of NSCs after Aβ treatment. Oxidative stress, ER stress, and mitochondrial dysfunction induced by Aβ could be restored by DUSP6 overexpression. Additionally, the Aβ-induced ERK1/2 activation was reversed. In summary, DUSP6 might have a neuroprotective effect on Aβ-induced cytotoxicity, probably via ERK1/2 activation. View Full-Text
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Liao, W.; Zheng, Y.; Fang, W.; Liao, S.; Xiong, Y.; Li, Y.; Xiao, S.; Zhang, X.; Liu, J. Dual Specificity Phosphatase 6 Protects Neural Stem Cells from β-Amyloid-Induced Cytotoxicity through ERK1/2 Inactivation. Biomolecules 2018, 8, 181.
Liao W, Zheng Y, Fang W, Liao S, Xiong Y, Li Y, Xiao S, Zhang X, Liu J. Dual Specificity Phosphatase 6 Protects Neural Stem Cells from β-Amyloid-Induced Cytotoxicity through ERK1/2 Inactivation. Biomolecules. 2018; 8(4):181.Chicago/Turabian Style
Liao, Wang; Zheng, Yuqiu; Fang, Wenli; Liao, Shaowei; Xiong, Ying; Li, Yi; Xiao, Songhua; Zhang, Xingcai; Liu, Jun. 2018. "Dual Specificity Phosphatase 6 Protects Neural Stem Cells from β-Amyloid-Induced Cytotoxicity through ERK1/2 Inactivation." Biomolecules 8, no. 4: 181.
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