Dexamethasone Enhances Oxidative Stress-Induced Cell Death in Murine Neural Stem Cells

Alzheimer’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.

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Microarray Analyses Support a Role for Nurr1 in Resistance to Oxidative Stress and Neuronal Differentiation in Neural Stem Cells

Stem Cells ◽

10.1634/stemcells.2006-0238 ◽

2007 ◽

Vol 25 (2) ◽

pp. 511-519 ◽

Cited By ~ 23

Author(s):

Kyle M. Sousa ◽

Helena Mira ◽

Anita C. Hall ◽

Lottie Jansson-Sjöstrand ◽

Moriaki Kusakabe ◽

...

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Neural Stem Cells ◽

Neuronal Differentiation ◽

Microarray Analyses

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Effects of aluminum on the reduction of neural stem cells, proliferating cells, and differentiating neuroblasts in the dentate gyrus of D-galactose-treated mice via increasing oxidative stress

Journal of Veterinary Science ◽

10.4142/jvs.2016.17.2.127 ◽

2016 ◽

Vol 17 (2) ◽

pp. 127 ◽

Cited By ~ 2

Author(s):

Sung Min Nam ◽

Jong Whi Kim ◽

Dae Young Yoo ◽

Woosuk Kim ◽

Hyo Young Jung ◽

...

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Neural Stem Cells ◽

Dentate Gyrus ◽

Proliferating Cells

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Sensitive-stage embryo irradiation affects embryonic neuroblasts and adult motor function

Molecular & Cellular Toxicology ◽

10.1007/s13273-021-00212-y ◽

2022 ◽

Author(s):

Ram Wagle ◽

Young-Han Song

Keyword(s):

Stem Cells ◽

Cell Death ◽

Neural Stem Cells ◽

Motor Function ◽

Radiation Sensitivity ◽

Embryonic Lethality ◽

Apoptotic Cells ◽

Childhood Malignancies ◽

Sensitive Stage ◽

Stage Embryo

Abstract Background Cranial radiation therapy for treating childhood malignancies in the central nervous system or accidental radiation exposure may result in neurological side effects in surviving adults. As tissue homeostasis is maintained by stem cells, understanding the effect of radiation on neural stem cells will provide clues for managing the neurological effects. Drosophila embryos were used as a model system whose sensitivity to irradiation-induced cell death changes from the sensitive to resistant stage during development. Objective Drosophila embryos at the radiation-sensitive stage were irradiated at various doses and the radiation sensitivity was tested regarding the appearance of apoptotic cells in the embryos and the embryonic lethality. Cell fates of the neural stem cells called neuroblasts (NBs) and adult motor function after irradiation were also investigated. Result Irradiation of Drosophila embryos at the radiation-sensitive stage resulted in a dose-dependent increase in the number of embryos containing apoptotic cells 75 min after treatment starting at 3 Gy. Embryonic lethality assayed by hatch rate was induced by 1 Gy irradiation, which did not induce cell death. Notably, no apoptosis was detected in NBs up to 2 h after irradiation at doses as high as 40 Gy. At 3 h after irradiation, as low as 3 Gy, the number of NBs marked by Dpn and Klu was decreased by an unidentified mechanism regardless of the cell death status of the embryo. Furthermore, embryonic irradiation at 3 Gy, but not 1 Gy, resulted in locomotor defects in surviving adults. Conclusion Embryonic NBs survived irradiation at doses as high as 40 Gy, while cells in other parts of the embryos underwent apoptosis at doses higher than 3 Gy within 2 h after treatment. Three hours after exposure to a minimum dose of 3 Gy, the number of NBs marked by Dpn and Klu decreased, and the surviving adults exhibited defects in locomotor ability.

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Modulation of calcium-induced cell death in human neural stem cells by the novel peptidylarginine deiminase–AIF pathway

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ◽

10.1016/j.bbamcr.2014.02.018 ◽

2014 ◽

Vol 1843 (6) ◽

pp. 1162-1171 ◽

Cited By ~ 25

Author(s):

Kin Pong U ◽

Venkataraman Subramanian ◽

Antony P. Nicholas ◽

Paul R. Thompson ◽

Patrizia Ferretti

Keyword(s):

Stem Cells ◽

Cell Death ◽

Neural Stem Cells ◽

The Novel ◽

Peptidylarginine Deiminase ◽

Human Neural Stem Cells

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Adipose-Derived Mesenchymal Stem Cells Migrate and Rescue RPE in the Setting of Oxidative Stress

Stem Cells International ◽

10.1155/2018/9682856 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Aya Barzelay ◽

Shira Weisthal Algor ◽

Anat Niztan ◽

Sebastian Katz ◽

Moshe Benhamou ◽

...

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Cell Death ◽

Mesenchymal Stem Cells ◽

Conditioned Medium ◽

Early Passage ◽

Systemic Injection ◽

Rpe Cells

Oxidative stress leads to the degeneration of retinal pigment epithelial (RPE) and photoreceptor cells. We evaluated the potential of adipose-derived mesenchymal stem cells (ASCs) as a therapeutic tool by studying the migration capacity of ASCs in vitro and their protective effect against RPE cell death under oxidative stress in vitro and in vivo. ASCs exhibited enhanced migration when exposed to conditioned medium of oxidative stressed RPE cells obtained by hydrogen peroxide. Migration-related axis SDF-1/CXCR4 was studied, and upregulation of SDF-1 in stressed RPE and of CXCR4 in ASCs was detected. Moreover, ASCs’ conditioned medium prevented H2O2-induced cell death of RPE cells. Early passage ASCs had high expression level of HGF, low VEGF levels, and unmodulated IL-1β levels, compared to late passage ASCs. Thus, early passage ASCs show the potential to migrate towards damaged RPE cells and protect them in a paracrine manner from cell death induced by oxidative stress. In vivo, mice received systemic injection of NaIO3, and 72 h later, ASCs were transplanted in the subretinal space. Seven days after ASC transplantation, the eyes were enucleated fixed and frozen for immunohistochemical analysis. Under such conditions, ASC-treated mice showed preservation of nuclear layers in the outer nuclear layer and stronger staining of RPE and photoreceptor layer, compared to PBS-treated mice. Taken together, our results indicate that ASCs are able to home in on damaged RPE cells and protect against damage to the RPE and PR layers caused by oxidative stress. These data imply the potential that ASCs have in regenerating RPE under oxidative stress, providing the basis for a therapeutic approach to retinal degeneration diseases related to oxidative stress that could help save the eyesight of millions of people worldwide.

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