Dataset Information

Global analysis of ginsenoside Rg1 protective effects in β-amyloid-treated neuronal cells.

ABSTRACT:

Background

A number of reports have described the protective effects of ginsenoside Rg1 (Rg1) in Alzheimer's disease (AD). However, the protective mechanisms of Rg1 in AD remain elusive.

Methods

To investigate the potential mechanisms of Rg1 in β-amyloid peptide-treated SH-SY5Y cells, a comparative proteomic analysis was performed using stable isotope labeling with amino acids in cell culture combined with nano-LC-MS/MS.

Results

We identified a total of 1,149 proteins in three independent experiments. Forty-nine proteins were significantly altered by Rg1 after exposure of the cells to β-amyloid peptides. The protein interaction network analysis showed that these altered proteins were clustered in ribosomal proteins, mitochondria, the actin cytoskeleton, and splicing proteins. Among these proteins, mitochondrial proteins containing HSD17B10, AARS2, TOMM40, VDAC1, COX5A, and NDUFA4 were associated with mitochondrial dysfunction in the pathogenesis of AD.

Conclusion

Our results suggest that mitochondrial proteins may be related to the protective mechanisms of Rg1 in AD.

SUBMITTER: Shim JS

PROVIDER: S-EPMC5628347 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Publications

Global analysis of ginsenoside Rg1 protective effects in β-amyloid-treated neuronal cells.

Shim Ji Seon JS Song Min-Young MY Yim Sung-Vin SV Lee Seung-Eun SE Park Kang-Sik KS

Journal of ginseng research 20161208 4

<h4>Background</h4>A number of reports have described the protective effects of ginsenoside Rg1 (Rg1) in Alzheimer's disease (AD). However, the protective mechanisms of Rg1 in AD remain elusive.<h4>Methods</h4>To investigate the potential mechanisms of Rg1 in β-amyloid peptide-treated SH-SY5Y cells, a comparative proteomic analysis was performed using stable isotope labeling with amino acids in cell culture combined with nano-LC-MS/MS.<h4>Results</h4>We identified a total of 1,149 proteins in th ...[more]

PMID: 29021705

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Project description:Depression is considered a neuropsychiatric disease associated with various neuronal changes within specific brain regions. We previously reported that ginsenoside-Rg1, a potential neuroprotective agent extracted from ginseng, significantly alleviated depressive-like disorders induced by chronic stress in rats. However, the mechanisms by which ginsenoside-Rg1 exerts its neuroprotective effects in depression remain largely uncharacterized. In the present study we confirm that ginsenoside-Rg1 significantly prevented the antidepressant-like effects in a rat model of chronic unpredictable mild stress (CUMS) and report on some of the underlying mechanisms associated with this effect. Specifically, we found that chronic pretreatment with ginsenoside-Rg1 prior to stress exposure significantly suppressed inflammatory pathway activity via alleviating the overexpression of proinflammatory cytokines and the activation of microglia and astrocytes. These effects were accompanied with an attenuation of dendritic spine and synaptic deficits as associated with an upregulation of synaptic-related proteins in the ventral medial prefrontal cortex (vmPFC). In addition, ginsenoside-Rg1 inhibited neuronal apoptosis induced by CUMS exposure, increased Bcl-2 expression and decreased cleaved Caspase-3 and Caspase-9 expression within the vmPFC region. Furthermore, ginsenoside-Rg1 could increase the nuclear factor erythroid 2-related factor (Nrf2) expression and inhibit p38 mitogen-activated protein kinase (p-p38 MAPK) and nuclear factor κB (NF-κB) p65 subunit activation within the vmPFC. Taken together, these results suggest that the neuroprotective effects of ginsenoside-Rg1, which may assume the antidepressant-like effect in this animal model of depression, appears to result from amelioration of a CUMS-dependent neuronal deterioration within the vmPFC. Moreover, they also provide support for the therapeutic potential of ginsenoside-Rg1 in the treatment of stress-related mental disorders.

Project description:Oxidative stress-induced cytoskeletal dysfunction of neurons has been implicated as a crucial cause of cell apoptosis or death in the central nervous system (CNS) diseases, such as neurodegenerative and psychiatric diseases. The application of neuroprotectants rescuing the neurons from cytoskeletal damage and apoptosis can be a potential treatment for these CNS diseases. Ginsenoside Rg1 (Rg1), one of the major active components of ginseng, has been reported possessing notable neuroprotective activities. However, there is rare report about its effect on cytoskeleton and its undergoing mechanism. The current study is to reveal the regulatory effects of Rg1 on cytoskeletal and morphological lesion in oxidative stress-induced neuronal apoptosis. The results demonstrated that pre-treatment with Rg1 (0.1-10 μM) attenuated hydrogen peroxide (H2O2)-induced neuronal apoptosis and oxidative stress through reducing the intracellular reactive oxygen species (ROS) production and methane dicarboxylic aldehyde (MDA) level. The Rg1 treatment also abolished H2O2-induced morphological changes, including cell rounding, membrane blebbing, neurite retraction and nuclei condensation, which were generated by myosin IIA-actin interaction. These effects were mediated via the down-regulation of caspase-3, ROCK1 (Rho-associated kinase1) activation and myosin light chain (MLC, Ser-19) phosphorylation. Furthermore, inhibiting myosin II activity with blebbistatin partly blocked the neuroprotective effects of Rg1. The computer-aided homology modelling revealed that Rg1 preferentially positioned in the actin binding cleft of myosin IIA and might block the binding of myosin IIA to actin filaments. Accordingly, the neuroprotective mechanism of Rg1 is related to the activity that inhibits myosin IIA-actin interaction and the caspase-3/ROCK1/MLC signaling pathway. These findings put some insights into the unique neuroprotective properties of Rg1 associated with the regulation of myosin IIA-actin cytoskeletal structure under oxidative stress and provide experimental evidence for Rg1 in CNS diseases.

Project description:BackgroundGinsenoside Rg1 was shown to exert ligand-independent activation of estrogen receptor (ER) via mitogen-activated protein kinase-mediated pathway. Our study aimed to delineate the mechanisms by which Rg1 activates the rapid ER signaling pathways.MethodsER-positive human breast cancer MCF-7 cells and ER-negative human embryonic kidney HEK293 cells were treated with Rg1 (10-12M, 10-8M), 17ß-estradiol (10-8M), or vehicle. Immunoprecipitation was conducted to investigate the interactions between signaling protein and ER in MCF-7 cells. To determine the roles of these signaling proteins in the actions of Rg1, small interfering RNA or their inhibitors were applied.ResultsRg1 rapidly induced ERα translocation to plasma membrane via caveolin-1 and the formation of signaling complex involving linker protein (Shc), insulin-like growth factor-I receptor, modulator of nongenomic activity of ER (MNAR), ERα, and cellular nonreceptor tyrosine kinase (c-Src) in MCF-7 cells. The induction of extracellular signal-regulated protein kinase and mitogen-activated protein kinase kinase (MEK) phosphorylation in MCF-7 cells by Rg1 was suppressed by cotreatment with small interfering RNA against these signaling proteins. The stimulatory effects of Rg1 on MEK phosphorylation in these cells were suppressed by both PP2 (Src kinase inhibitor) and AG1478 [epidermal growth factor receptor (EGFR) inhibitor]. In addition, Rg1-induced estrogenic activities, EGFR and MEK phosphorylation in MCF-7 cells were abolished by cotreatment with G15 (G protein-coupled estrogen receptor-1 antagonist). The increase in intracellular cyclic AMP accumulation, but not Ca mobilization, in MCF-7 cells by Rg1 could be abolished by G15.ConclusionGinsenoside Rg1 exerted estrogenic actions by rapidly inducing the formation of ER containing signalosome in MCF-7 cells. Additionally, Rg1 could activate EGFR and c-Src ER-independently and exert estrogenic effects via rapid activation of membrane-associated ER and G protein-coupled estrogen receptor.

Dataset Information

Global analysis of ginsenoside Rg1 protective effects in β-amyloid-treated neuronal cells.

Background

Methods

Results

Conclusion

Publications

Global analysis of ginsenoside Rg1 protective effects in β-amyloid-treated neuronal cells.

Similar Datasets

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