Recombinant human erythropoietin reduces aggregation of mutant Cu/Zn-binding superoxide dismutase (SOD1) in NSC-34 cells

Cho, Goang Won; Kim, Ga Young; Baek, Soojeong; Heejaung, Kim; Kim, Taikon; Kim, Hee Jin; Kim, Seung Hyun

doi:10.1016/j.neulet.2011.09.008

Cited by 11 publications

(9 citation statements)

References 20 publications

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“…A similar effect was observed in a recent study using NSC-34 neuronal cells over-expressing the SOD1 G093A gene [34]. An in vivo study using adult SOD1 G93A mice showed that the number of BrdU-pulse labeled cells was significantly decreased in the forebrain regions [35].…”

Section: Discussionsupporting

confidence: 85%

Male-Specific Differences in Proliferation, Neurogenesis, and Sensitivity to Oxidative Stress in Neural Progenitor Cells Derived from a Rat Model of ALS

Strykowski

Meyer

et al. 2012

PLoS ONE

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Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor dysfunction and the loss of large motor neurons in the spinal cord and brain stem. A clear genetic link to point mutations in the superoxide dismutase 1 (SOD1) gene has been shown in a small group of familial ALS patients. The exact etiology of ALS is still uncertain, but males have consistently been shown to be at a higher risk for the disease than females. Here we present male-specific effects of the mutant SOD1 transgene on proliferation, neurogenesis, and sensitivity to oxidative stress in rat neural progenitor cells (rNPCs). E14 pups were bred using SOD1G93A transgenic male rats and wild-type female rats. The spinal cord and cortex tissues were collected, genotyped by PCR using primers for the SOD1G93A transgene or the male-specific Sry gene, and cultured as neurospheres. The number of dividing cells was higher in male rNPCs compared to female rNPCs. However, SOD1G93A over-expression significantly reduced cell proliferation in male cells but not female cells. Similarly, male rNPCs produced more neurons compared to female rNPCs, but SOD1G93A over-expression significantly reduced the number of neurons produced in male cells. Finally we asked whether sex and SOD1G93A transgenes affected sensitivity to oxidative stress. There was no sex-based difference in cell viability after treatment with hydrogen peroxide or 3-morpholinosydnonimine, a free radical-generating agent. However, increased cytotoxicity by SOD1G93A over-expression occurred, especially in male rNPCs. These results provide essential information on how the mutant SOD1 gene and sexual dimorphism are involved in ALS disease progression.

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Section: Discussionsupporting

confidence: 85%

Male-Specific Differences in Proliferation, Neurogenesis, and Sensitivity to Oxidative Stress in Neural Progenitor Cells Derived from a Rat Model of ALS

Strykowski

Meyer

et al. 2012

PLoS ONE

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“…Cells were seeded at a concentration of 5 × 10 4 cells/ml and maintained at 37°C in a humidified atmosphere of 5% CO 2 . After 48 h in proliferation medium, differentiation was induced by changing medium for DMEM-F12 plus 1% of FBS-exosome depleted, 1% of non-essential amino acids (NEAA), 1% of Penicillin/Streptomycin and 0.5 mg/ml of G418, as indicated by Cho et al (2011). Cells were maintained in culture with differentiation medium for 4 days in vitro (DIV) to induce SOD1 accumulation (Vaz et al, 2015).…”

Section: Methodsmentioning

confidence: 99%

Exosomes from NSC-34 Cells Transfected with hSOD1-G93A Are Enriched in miR-124 and Drive Alterations in Microglia Phenotype

et al. 2017

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Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disorder affecting motor neurons (MNs). Evidences indicate that ALS is a non-cell autonomous disease in which glial cells participate in both disease onset and progression. Exosomal transfer of mutant copper-zinc superoxide dismutase 1 (mSOD1) from cell-to-cell was suggested to contribute to disease dissemination. Data from our group and others showed that exosomes from activated cells contain inflammatory-related microRNAs (inflamma-miRNAs) that recapitulate the donor cell. While glia-derived exosomes and their effects in neurons have been addressed by several studies, only a few investigated the influence of motor neuron (MN)-derived exosomes in other cell function, the aim of the present study. We assessed a set of inflamma-miRs in NSC-34 MN-like cells transfected with mutant SOD1(G93A) and extended the study into their derived exosomes (mSOD1 exosomes). Then, the effects produced by mSOD1 exosomes in the activation and polarization of the recipient N9 microglial cells were investigated. Exosomes in coculture with N9 microglia and NSC-34 cells [either transfected with either wild-type (wt) human SOD1 or mutant SOD1(G93A)] showed to be transferred into N9 cells. Increased miR-124 expression was found in mSOD1 NSC-34 cells and in their derived exosomes. Incubation of mSOD1 exosomes with N9 cells determined a sustained 50% reduction in the cell phagocytic ability. It also caused a persistent NF-kB activation and an acute generation of NO, MMP-2, and MMP-9 activation, as well as upregulation of IL-1β, TNF-α, MHC-II, and iNOS gene expression, suggestive of induced M1 polarization. Marked elevation of IL-10, Arginase 1, TREM2, RAGE, and TLR4 mRNA levels, together with increased miR-124, miR-146a, and miR-155, at 24 h incubation, suggest the switch to mixed M1 and M2 subpopulations in the exosome-treated N9 microglial cells. Exosomes from mSOD1 NSC-34 MNs also enhanced the number of senescent-like positive N9 cells. Data suggest that miR-124 is translocated from the mSOD1 MNs to exosomes, which determine early and late phenotypic alterations in the recipient N9-microglial cells. In conclusion, modulation of the inflammatory-associated miR-124, in mSOD1 NSC-34 MNs, with potential benefits in the cargo of their exosomes may reveal a promising therapeutic strategy in halting microglia activation and associated effects in MN degeneration.

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“…All media were purchased from GIBCO (GIBCO, USA). We stably overexpressed wild and mutant G93A superoxide dismutase 1 (SO D 1, NM_000454) in NSC-34 cell lines that were selected using 100 μg/mL geneticin [40]. Exogenous 22(S)-, 24-,25-, and 27-OHC (Sigma, USA) was dissolved in ethanol [41].…”

Section: Methodsmentioning

confidence: 99%

25-Hydroxycholesterol is involved in the pathogenesis of amyotrophic lateral sclerosis

et al. 2017

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This study aimed to evaluate the levels of three major hydroxycholesterols (24-, 25-, and 27-hydroxycholesterols) in the serum and cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS), as well as to show their role in the pathogenesis of ALS experimental models. The level of 25-hydroxycholesterol were higher in untreated ALS patients (n = 30) than in controls without ALS (n = 33) and ALS patients treated with riluzole (n = 9) both in their serum and CSF. The level of 25-hydroxycholesterol in the serum of ALS patients were significantly associated with their disease severity and rate of progression. In the motor neuron-like cell line (NSC34) with the human mutant G93A superoxide dismutase 1 gene (mSOD1-G93A), 25-hydroxycholesterol induced motor neuronal death/ apoptosis via glycogen synthase kinase-3β and liver X receptor pathways; riluzole treatment attenuated these effects. The expressions of enzymes that synthesize 25-hydroxycholesterol were significantly increased in the brains of early symptomatic mSOD1G93A mice. Our data, obtained from patients with ALS, a cellular model of ALS, and an animal model of ALS, suggests that 25-hydroxycholesterol could be actively involved in the pathogenesis of ALS, mostly in the early symptomatic disease stage, by mediating neuronal apoptosis.

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Recombinant human erythropoietin reduces aggregation of mutant Cu/Zn-binding superoxide dismutase (SOD1) in NSC-34 cells

Cited by 11 publications

References 20 publications

Male-Specific Differences in Proliferation, Neurogenesis, and Sensitivity to Oxidative Stress in Neural Progenitor Cells Derived from a Rat Model of ALS

Male-Specific Differences in Proliferation, Neurogenesis, and Sensitivity to Oxidative Stress in Neural Progenitor Cells Derived from a Rat Model of ALS

Exosomes from NSC-34 Cells Transfected with hSOD1-G93A Are Enriched in miR-124 and Drive Alterations in Microglia Phenotype

25-Hydroxycholesterol is involved in the pathogenesis of amyotrophic lateral sclerosis

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