Overexpression of alpha-synuclein promotes both cell proliferation and cell toxicity in human SH-SY5Y neuroblastoma cells

Rodríguez-Losada, Noéla; Rosa, Javier de la; Larriva, M. S. Arenas de; Wendelbo, Rune; Aguirre, José; Castresana, Javier S.; Ballaz, Santiago

doi:10.1016/j.jare.2020.01.009

Cited by 30 publications

(29 citation statements)

References 85 publications

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“…Indeed, our data confirm that most GOd diminished α-syn protein levels ( Figure 8 ), a protein induced by oxidative stress and involved in PD (Menges et al, 2017 ; Musgrove et al, 2019 ). Data that has been corroborated recently in studies with neuroblastoma SH5Y5 whose clones express a-Syn treated with Rot (Rodríguez-Losada et al, 2020 ). In our study, we find that PRGO-film diminished α-synuclein levels in DA cells exposed to Rot, whereas FRGO-film did not.…”

Section: Discussionmentioning

confidence: 53%

“…SN4741 cells were seeded at a concentration of 2.4 × 10 3 cells/cm 2 for 7 days for all the conditions. Then, the control and GOd treated cells were treated with 1.2 μM Rot in 0.1% DMSO for 24 h as previously described (Rodríguez-Losada et al, 2020 ). α-synuclein levels were measured by Western blot using a monoclonal α-synuclein antibody that identified a band of around 18 KDa and was a predicted to identify a band of 14.5 KDa (clone syn S211, Thermo-Fisher), polyclonal cFos antibody involved in identified with a band around 50 KDa and predicted band of 62 KDa (Cell Signaling).…”

Section: Methodsmentioning

confidence: 99%

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Graphene Oxide and Reduced Derivatives, as Powder or Film Scaffolds, Differentially Promote Dopaminergic Neuron Differentiation and Survival

et al. 2020

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Emerging scaffold structures made of carbon nanomaterials, such as graphene oxide (GO) have shown efficient bioconjugation with common biomolecules. Previous studies described that GO promotes the differentiation of neural stem cells and may be useful for neural regeneration. In this study, we examined the capacity of GO, full reduced (FRGO), and partially reduced (PRGO) powder and film to support survival, proliferation, differentiation, maturation, and bioenergetic function of a dopaminergic (DA) cell line derived from the mouse substantia nigra (SN4741). Our results show that the morphology of the film and the species of graphene (GO, PRGO, or FRGO) influences the behavior and function of these neurons. In general, we found better biocompatibility of the film species than that of the powder. Analysis of cell viability and cytotoxicity showed good cell survival, a lack of cell death in all GO forms and its derivatives, a decreased proliferation, and increased differentiation over time. Neuronal maturation of SN4741 in all GO forms, and its derivatives were assessed by increased protein levels of tyrosine hydroxylase (TH), dopamine transporter (DAT), the glutamate inward rectifying potassium channel 2 (GIRK2), and of synaptic proteins, such as synaptobrevin and synaptophysin. Notably, PRGO-film increased the levels of Tuj1 and the expression of transcription factors specific for midbrain DA neurons, such as Pitx3, Lmx1a, and Lmx1b. Bioenergetics and mitochondrial dysfunction were evaluated by measuring oxygen consumption modified by distinct GO species and were different between powder and film for the same GO species. Our results indicate that PRGO-film was the best GO species at maintaining mitochondrial function compared to control. Finally, different GO forms, and particularly PRGO-film was also found to prevent the loss of DA cells and the decrease of the α-synuclein (α-syn) in a molecular environment where oxidative stress has been induced to model Parkinson's disease. In conclusion, PRGO-film is the most efficient graphene species at promoting DA differentiation and preventing DA cell loss, thus becoming a suitable scaffold to test new drugs or develop constructs for Parkinson's disease cell replacement therapy.

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Section: Discussionmentioning

confidence: 53%

Section: Methodsmentioning

confidence: 99%

Graphene Oxide and Reduced Derivatives, as Powder or Film Scaffolds, Differentially Promote Dopaminergic Neuron Differentiation and Survival

et al. 2020

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“…Indeed, our data confirm that most GOd diminished α-syn protein levels (Figure 8), a protein induced by oxidative stress and involved in PD (Menges et al, 2017;Musgrove et al, 2019). Data that has been corroborated recently in studies with neuroblastoma SH5Y5 whose clones express a-Syn treated with Rot (Rodríguez-Losada et al, 2020). In our study, we find that PRGO-film diminished α-synuclein levels in DA cells exposed to Rot, whereas FRGO-film did not.…”

Section: Discussionsupporting

confidence: 90%

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“…Downregulation of SNCA correlated with decreased overall survival. In the most recent experimental studies with the human neuroblastoma SH-SY5Y cell line, it has been proved that the effect of increased expression of SNCA depends on its stage [ 163 ]. SNCA overexpression resulted in inducing increased cell vulnerability to oxidative stress.…”

Section: Cancer and α-Synucleinmentioning

confidence: 99%

The Links between Parkinson’s Disease and Cancer

et al. 2020

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Epidemiologic studies indicate a decreased incidence of most cancer types in Parkinson’s disease (PD) patients. However, some neoplasms are associated with a higher risk of occurrence in PD patients. Both pathologies share some common biological pathways. Although the etiologies of PD and cancer are multifactorial, some factors associated with PD, such as α-synuclein aggregation; mutations of PINK1, PARKIN, and DJ-1; mitochondrial dysfunction; and oxidative stress can also be involved in cancer proliferation or cancer suppression. The main protein associated with PD, i.e., α-synuclein, can be involved in some types of neoplastic formations. On the other hand, however, its downregulation has been found in the other cancers. PINK1 can act as oncogenic or a tumor suppressor. PARKIN dysfunction may lead to some cancers’ growth, and its expression may be associated with some tumors’ suppression. DJ-1 mutation is involved in PD pathogenesis, but its increased expression was found in some neoplasms, such as melanoma or breast, lung, colorectal, uterine, hepatocellular, and nasopharyngeal cancers. Both mitochondrial dysfunction and oxidative stress are involved in PD and cancer development. The aim of this review is to summarize the possible associations between PD and carcinogenesis.

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Overexpression of alpha-synuclein promotes both cell proliferation and cell toxicity in human SH-SY5Y neuroblastoma cells

Cited by 30 publications

References 85 publications

Graphene Oxide and Reduced Derivatives, as Powder or Film Scaffolds, Differentially Promote Dopaminergic Neuron Differentiation and Survival

Graphene Oxide and Reduced Derivatives, as Powder or Film Scaffolds, Differentially Promote Dopaminergic Neuron Differentiation and Survival

Image_4.TIF

The Links between Parkinson’s Disease and Cancer

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