Emodin Protects SH-SY5Y Cells Against Zinc-Induced Synaptic Impairment and Oxidative Stress Through the ERK1/2 Pathway

Chen, Qian; Lai, Chencen; Fa, Chen; Ding, Yuanting; Zhou, Yiyuan; Su, Shengfa; Ni, Ruiqing; Tang, Zhi

doi:10.3389/fphar.2022.821521

Cited by 10 publications

(8 citation statements)

References 60 publications

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“…For this reason, EVs are implicated in diseases strictly linked to oxidative stress, for instance neurodegenerative disorders ( Fowler and Hill, 2019 ; Meldolesi, 2021 ; Qi et al, 2021 ). Human neuroblastoma SH-SY5Y cell line, widely used as a model to investigate neurodegeneration and oxidative stress ( Martínez et al, 2020 ; Greco et al, 2021 ; Chen et al, 2022 ), has been chosen to perform a comparative morphological and quantitative analysis of membrane budding and isolated microvesicles-like vesicles (MVs), in physiological conditions (control) or under oxidative stress (H2O2-induced), by electron microscopy (EM) and atomic force microscopy (AFM). The main goal of this work was to define a new method to study EVs morphological features and their alterations under stress conditions, evaluating the efficacy of the system compared to conventional methods.…”

Section: Introductionmentioning

confidence: 99%

High-resolution atomic force microscopy as a tool for topographical mapping of surface budding

Sbarigia

Tacconi²,

Mura³

et al. 2022

Front. Cell Dev. Biol.

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Extracellular vesicles (EVs) are membranous nanoparticles secreted by almost all cell types. Reflecting the physiopathological state of the parental cell, EVs circulate in all body fluids, reaching distant cell targets and delivering different bioactive cargoes. As biological carriers, EVs influence their microenvironment altering cellular responses, being considered promising biomarkers for both physiological and pathological conditions. EVs are heterogeneous in terms of size and composition, depending on cell type and exposure to stimuli, and different methods have been developed to characterize their morphological, biophysical, and biochemical features. Among them, electron microscopy (EM) is the main technique used, however, the lack of standardized protocols makes it difficult to characterize EVs with a good reproducibility, thus using multiple approaches may represent a way to obtain more precise information. Furthermore, the relationship between architecture and function, not only in a molecular, but also in a cellular level, is gaining growing emphasis, characterizing morphometric parameters may represent a distinct, but effective approach to study the physiopathological state of the cell. Atomic force microscopy (AFM), may represent a promising method to study in detail EVs dynamics throughout the cell surface and its variations related to the physiological state, overcoming the limits of EM, and providing more reliable information. In this study, human neuroblastoma SH-SY5Y cell line, a cellular model to investigate neurodegeneration and oxidative stress, has been used to perform a comparative morphological and quantitative analysis of membrane budding and isolated large vesicles-enriched (microvesicles-like vesicles; MVs) fraction from control or oxidative stressed cells. Our main goal was to build up a methodology to characterize EVs morphology and spatial distribution over the cell surface in different physiological conditions, and to evaluate the efficacy of AFM against conventional EM. Interestingly, both microscopy techniques were effective for this analysis, but AFM allowed to reveal a differential profiling of plasma membrane budding between the physiological and the stress condition, indicating a potential relationship between mechanical characteristics and functional role. The results obtained may provide interesting perspectives for the use of AFM to study EVs, validating a morphometric approach to understand the pathophysiological state of the cell related to EVs trafficking.

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Section: Introductionmentioning

confidence: 99%

High-resolution atomic force microscopy as a tool for topographical mapping of surface budding

Sbarigia

Tacconi²,

Mura³

et al. 2022

Front. Cell Dev. Biol.

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“…Quercetin have demonstrated the effect on other cellular types in addition to neurons; such as alleviateing Aβ-associated oligodendrocyte progenitor cell senescence and cognitive deficits in APP/PS1 model of AD amyloidosis (Zhang et al, 2019), involved in microglia associated reduction of the accumulation of Aβ plaques and inflammation in AD model mice (Sabogal-Guaqueta et al, 2015;Wang et al, 2022). Further studies are needed to employ a co-culture model with neurons, astrocytes and microglia to study the effect of quercetin.…”

Section: Discussionmentioning

confidence: 99%

“…Cell viability was measured by a cell counting kit-8 (CCK-8) (MedChemExpress LLC, China) according to the manufacturer’s instructions. A total of 5×10 3 cells were seeded into 96-well plates (Chen et al, 2022; Tang et al, 2021). After being treated, 10 μl of CCK-8 reagent and 100 μl of medium were added to each well, and incubated for 1 h at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

Quercetin reduces APP expression, oxidative stress and mitochondrial dysfunction in the N2a/APPswe cells via ERK1/2 and AKT pathways

Tang

Guo

Peng

et al. 2022

Preprint

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Abnormal amyloid-β (Aβ) abnormal accumulation and oxidative stress play important roles in Alzheimer′ disease (AD). Quercetin has been reported to possess antioxidant and anti-inflammatory properties, and thus of therapeutic interests for neurodegenerative disorders. In the present study, we aimed to characterize the mechanisms by which quercetin exerts neuroprotective effects in murine neuroblastoma N2a cells stably expressing human Swedishh mutant amyloid precursor protein (APP). Quercetin treatment exhibited low cytoxicity, attenuated APP expression and APP-induced oxidative neurotoxicity in N2a/APP cells. We found that quercetin effected via the down-regulation of phospho-extracellular signal regulated protein kinase (p-ERK1/2) pathway and up-regulation of phospho-protein kinase B (p-AKT) pathway in N2a/APP cells. In addition, quercetin ameliorated the elevated levels of reactive oxygen species using DCFH-DA flow-cytometry in N2a/APP cells, lipid peroxidation using (4-HNE), and DNA oxidation (8-OHdG assays). Quercetin ameliorated the loss of mitochondrial membrane potential using JC-1 fluorescence assay in N2a/APP cells in a dose-dependent mannor. In conclusion, we domenstrated the neuroprotective effects of quercetin against the APP expression induced oxidative neurotoxicity, impairment of mitochondrial function and oxidative stress through inactivation of the ERK1/2 signaling pathway and activation of AKT signaling pathways.

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“…Cell viability was measured using a cell counting kit-8 (CCK-8) (MedChemExpress, USA) as previously described [36, 37]. In brief, a total of 5×10 3 cells were seeded into 96-well plates.…”

Section: Methodsmentioning

confidence: 99%

Myricetin protected against Aβ oligomer-induced synaptic impairment, mitochondrial function and oxidative stress in SH-SY5Y cells via ERK1/2/GSK-3β pathways

Wang

Tang

Deng

et al. 2023

Preprint

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Alzheimers disease is characterized by abnormal β-amyloid (Aβ) plaque accumulation, tau hyperphosphorylation, reactive oxidative stress, mitochondrial dysfunction and synaptic loss. Myricetin, a dietary flavonoid, has been shown to have neuroprotective effects in vitro and in vivo. Here, we aimed to elucidate the mechanism and pathways involved in myricetin protective effect on the toxicity induced by the Aβ42 oligomer. Neuronal SH-SY5Y cells were pretreated with myricetin before incubation with Aβ42 oligomer. The levels of pre- and post-synaptic proteins, mitochondrial division and fusion proteins, glycogen synthase kinase-3β (GSK-β) and extracellular regulated kinase (ERK) 1/2 were assessed by Western blotting. Flow cytometry assays for mitochondrial membrane potential (JC1) and reactive oxidative stress, as well immunofluorescence staining for lipid peroxidation (4-HNE) and DNA oxidation (8-OHdG), were performed. We found that myricetin prevented Aβ42 oligomer-induced tau phosphorylation and the reduction in pre/postsynaptic proteins. In addition, myricetin reduced reactive oxygen species generation, lipid peroxidation, and DNA oxidation induced by the Aβ42 oligomer. Moreover, myricetin prevented the Aβ42 oligomer-induced reduction in mitochondrial fusion proteins (mitofusin-1, mitofusin-2), fission protein (dynamin-related protein 1) phosphorylation, and mitochondrial membrane potential via the associated GSK-3β and ERK 1/2 signaling pathways. In conclusion, this study provides new insight into the neuroprotective mechanism of myricetin against Aβ42 oligomer-induced toxicity.

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Emodin Protects SH-SY5Y Cells Against Zinc-Induced Synaptic Impairment and Oxidative Stress Through the ERK1/2 Pathway

Cited by 10 publications

References 60 publications

High-resolution atomic force microscopy as a tool for topographical mapping of surface budding

High-resolution atomic force microscopy as a tool for topographical mapping of surface budding

Quercetin reduces APP expression, oxidative stress and mitochondrial dysfunction in the N2a/APPswe cells via ERK1/2 and AKT pathways

Myricetin protected against Aβ oligomer-induced synaptic impairment, mitochondrial function and oxidative stress in SH-SY5Y cells via ERK1/2/GSK-3β pathways

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