Korean Red Ginseng Inhibits Amyloid-β-Induced Apoptosis and Nucling Expression in Human Neuronal Cells

Pharmacology ◽  
2020 ◽  
Vol 105 (9-10) ◽  
pp. 586-597 ◽  
Author(s):  
Suyun Choi ◽  
Joo Weon Lim ◽  
Hyeyoung Kim
Keyword(s):  
Mitochondrial Dysfunction ◽  
Neuronal Apoptosis ◽  
Neuronal Cells ◽  
Neuronal Cell Death ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Dependent Manner ◽  
Red Ginseng ◽  
Korean Red Ginseng ◽  
Human Neuronal Cells

<b><i>Introduction:</i></b> The accumulation of amyloid-β (Aβ) plaque in the brain is a characteristic feature of Alzheimer’s disease (AD) and the cause of fatal oxidative damage to neuronal cells. Korean red ginseng (RG) is used extensively in traditional medicine and is known to have anti-oxidative and anti-inflammatory properties. <b><i>Objective:</i></b> This study aims to investigate whether Korean RG extract inhibits Aβ-induced neuronal apoptosis. <b><i>Methods:</i></b> Human neuronal cells (SH-SY5Y cells) were stimulated with Aβ (5 μmol/L) and treated with RG dissolved in phosphate-buffered saline (0.2, 2, 20 μg/mL). <b><i>Results:</i></b> RG suppressed the reduction of cell viability and the increase in apoptotic factors (Bax/Bcl-2 ratio and caspase-3 activity) in Aβ-treated cells. RG suppressed Aβ-induced increases in intracellular and mitochondrial reactive oxygen species (ROS) levels and mitochondrial dysfunction (determined by low mitochondrial membrane potential and oxygen consumption rate) in a dose-dependent manner. RG inhibited nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) activation and expression of the pro-apoptotic gene Nucling in Aβ-treated cells. <b><i>Conclusion:</i></b> RG confers protection against neuronal apoptosis by reducing ROS levels and suppressing mitochondrial dysfunction and NF-κB activation, which results in suppression of NF-κB-mediated activation of Nucling expression in Aβ-treated cells. Supplementation with RG may be beneficial for preventing Aβ-induced neuronal cell death associated with AD.

Lipocalin-type prostaglandin D synthase protects against oxidative stress-induced neuronal cell death

2012 ◽  
Vol 443 (1) ◽  
pp. 75-84 ◽  
Author(s):  
Ayano Fukuhara ◽  
Mao Yamada ◽  
Ko Fujimori ◽  
Yuya Miyamoto ◽  
Toshihide Kusumoto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neuroblastoma Cell ◽  
Neuronal Cells ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Dependent Manner ◽  
Functional Protein ◽  
Prostaglandin D Synthase ◽  
Induced Apoptosis

L-PGDS [lipocalin-type PGD (prostaglandin D) synthase] is a dual-functional protein, acting as a PGD2-producing enzyme and a lipid transporter. L-PGDS is a member of the lipocalin superfamily and can bind a wide variety of lipophilic molecules. In the present study we demonstrate the protective effect of L-PGDS on H2O2-induced apoptosis in neuroblastoma cell line SH-SY5Y. L-PGDS expression was increased in H2O2-treated neuronal cells, and the L-PGDS level was highly associated with H2O2-induced apoptosis, indicating that L-PGDS protected the neuronal cells against H2O2-mediated cell death. A cell viability assay revealed that L-PGDS protected against H2O2-induced cell death in a concentration-dependent manner. Furthermore, the titration of free thiols in H2O2-treated L-PGDS revealed that H2O2 reacted with the thiol of Cys65 of L-PGDS. The MALDI–TOF (matrix-assisted laser-desorption ionization–time-of-flight)-MS spectrum of H2O2-treated L-PGDS showed a 32 Da increase in the mass relative to that of the untreated protein, showing that the thiol was oxidized to sulfinic acid. The binding affinities of oxidized L-PGDS for lipophilic molecules were comparable with those of untreated L-PGDS. Taken together, these results demonstrate that L-PGDS protected against neuronal cell death by scavenging reactive oxygen species without losing its ligand-binding function. The novel function of L-PGDS could be useful for the suppression of oxidative stress-mediated neurodegenerative diseases.

scholarly journals Caffeine Potentiates Ethanol-Induced Neurotoxicity Through mTOR/p70S6K/4E-BP1 Inhibition in SH-SY5Y Cells

2020 ◽  
Vol 39 (2) ◽  
pp. 131-140
Author(s):  
Pongsak Sangaunchom ◽  
Permphan Dharmasaroja
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Neuronal Cells ◽  
Neuronal Cell Death ◽  
Neuroblastoma Cells ◽  
Neuronal Cell ◽  
Apoptotic Cell Death ◽  
Dependent Manner ◽  
Ethanol Pretreatment ◽  
Marked Cell

Caffeine is a popular psychostimulant, which is frequently consumed with ethanol. However, the effects of caffeine on neuronal cells constantly exposed to ethanol have not been investigated. Apoptosis and oxidative stress occurring in ethanol-induced neurotoxicity were previously associated with decreased phosphorylation of the mTOR/p70S6K/4E-BP1 signaling proteins. Evidence also suggested that caffeine inhibits the mTOR pathway. In this study, human SH-SY5Y neuroblastoma cells were exposed to caffeine after pretreatment for 24 hours with ethanol. Results indicated that both ethanol and caffeine caused neuronal cell death in a dose- and time-dependent manner. Exposure to 20-mM caffeine for 24 hours magnified reduced cell viability and enhanced apoptotic cell death induced by 200 mM of ethanol pretreatment. The phosphorylation of mTOR, p70S6K, and 4E-BP1 markedly decreased in cells exposed to caffeine after ethanol pretreatment, associated with a decrease of the mitochondrial membrane potential (ΔΨm). These findings suggested that caffeine treatment after neuronal cells were exposed to ethanol resulted in marked cell damages, mediated through enhanced inhibition of mTOR/p70S6K/4E-BP1 signaling leading to impaired ΔΨm and, eventually, apoptotic cell death.

scholarly journals Human Immunodeficiency Virus Type 1 Vpr Induces Apoptosis in Human Neuronal Cells

2000 ◽  
Vol 74 (20) ◽  
pp. 9717-9726 ◽  
Author(s):  
Charvi A. Patel ◽  
Muhammad Mukhtar ◽  
Roger J. Pomerantz
Keyword(s):  
Cell Line ◽  
Neuronal Apoptosis ◽  
Neuronal Cells ◽  
Caspase 8 ◽  
Dependent Manner ◽  
Human Neurons ◽  
Induced Apoptosis ◽  
Human Neuronal Cells ◽  
Nt2 Cells ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) causes AIDS dementia complex (ADC) in certain infected individuals. Recent studies have suggested that patients with ADC have an increased incidence of neuronal apoptosis leading to neuronal dropout. Of note, a higher level of the HIV-1 accessory protein Vpr has been detected in the cerebrospinal fluid of AIDS patients with neurological disorders. Moreover, extracellular Vpr has been shown to form ion channels, leading to cell death of cultured rat hippocampal neurons. Based on these previous findings, we first investigated the apoptotic effects of the HIV-1 Vpr protein on the human neuronal precursor NT2 cell line at a range of concentrations. These studies demonstrated that apoptosis induced by both Vpr and the envelope glycoprotein, gp120, occurred in a dose-dependent manner compared to protein treatment with HIV-1 integrase, maltose binding protein (MBP), and MBP-Vpr in the undifferentiated NT2 cells. For mature, differentiated neurons, apoptosis was also induced in a dose-dependent manner by both Vpr and gp120 at concentrations ranging from 1 to 100 ng/ml, as demonstrated by both the terminal deoxynucleotidyltransferase (Tdt)-mediated dUTP-biotin nick end labeling and Annexin V assays for apoptotic cell death. In order to clarify the intracellular pathways and molecular mechanisms involved in Vpr- and gp120-induced apoptosis in the NT2 cell line and differentiated mature human neurons, we then examined the cellular lysates for caspase-8 activity in these studies. Vpr and gp120 treatments exhibited a potent increase in activation of caspase-8 in both mature neurons and undifferentiated NT2 cells. This suggests that Vpr may be exerting selective cytotoxicity in a neuronal precursor cell line and in mature human neurons through the activation of caspase-8. These data represent a characterization of Vpr-induced apoptosis in human neuronal cells, and suggest that extracellular Vpr, along with other lentiviral proteins, may increase neuronal apoptosis in the CNS. Also, identification of the intracellular activation of caspase-8 in Vpr-induced apoptosis of human neuronal cells may lead to therapeutic approaches which can be used to combat HIV-1-induced neuronal apoptosis in AIDS patients with ADC.

scholarly journals A Newly Synthesized Rhamnoside Derivative Alleviates Alzheimer’s Amyloid-β-Induced Oxidative Stress, Mitochondrial Dysfunction, and Cell Senescence through Upregulating SIRT3

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Yi Li ◽  
Jing Lu ◽  
Xin Cao ◽  
Hongwei Zhao ◽  
Longfei Gao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Protein ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Cell Senescence ◽  
Metabolic Enzyme ◽  
Drug Candidate ◽  
Dependent Manner ◽  
Long Term Treatment

Oxidative stress-induced mitochondrial dysfunction and cell senescence are considered critical contributors to Alzheimer’s disease (AD), and oxidant/antioxidant imbalance has been a therapeutic target in AD. SIRT3 is a mitochondrial protein regulating metabolic enzyme activity by deacetylation and its downregulation is associated with AD pathology. In the present study, we showed that a newly synthesized rhamnoside derivative PL171 inhibited the generation of reactive oxidant species (ROS) induced by amyloid-β42 oligomers (Aβ42O), major AD pathological proteins. Moreover, the reduction of mitochondrial membrane potential (MMP) and the impairment of mitochondrial oxygen consumption triggered by Aβ42O were also prevented by PL171. Further experiments demonstrated that PL171 reduced the acetylation of mitochondrial proteins, and particularly the acetylation of manganese superoxide dismutase (MnSOD) and oligomycin-sensitivity-conferring protein (OSCP), two mitochondrial SIRT3 substrates, was suppressed by PL171. Mechanism studies revealed that PL171 upregulated SIRT3 and its upstream peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) under basal and Aβ42O-treated conditions. The inhibition of SIRT3 activity could eliminate the protective effects of PL171. Further, long-term treatment with Aβ42O increased the number of senescent neuronal cell, which was also alleviated by PL171 in a SIRT3-dependent manner. Taken together, our results indicated that PL171 rescued Aβ42O-induced oxidative stress, mitochondrial dysfunction, and cell senescence via upregulating SIRT3 and might be a potential drug candidate against AD.

Oxidative Stress: Major Threat in Traumatic Brain Injury

2018 ◽  
Vol 17 (9) ◽  
pp. 689-695 ◽  
Author(s):  
Nidhi Khatri ◽  
Manisha Thakur ◽  
Vikas Pareek ◽  
Sandeep Kumar ◽  
Sunil Sharma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mitochondrial Dysfunction ◽  
Calcium Influx ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Physical Assault ◽  
Mortality And Morbidity ◽  
Primary Injury

Background & Objective: Traumatic Brain Injury (TBI) is one of the major causes of mortality and morbidity worldwide. It represents mild, moderate and severe effects of physical assault to brain which may cause sequential, primary or secondary ramifications. Primary injury can be due to the first physical hit, blow or jolt to one of the brain compartments. The primary injury is then followed by secondary injury which leads to biochemical, cellular, and physiological changes like blood brain barrier disruption, inflammation, excitotoxicity, necrosis, apoptosis, mitochondrial dysfunction and generation of oxidative stress. Apart from this, there is also an immediate increase in glutamate at the synapses following severe TBI. Excessive glutamate at synapses in turn activates corresponding NMDA and AMPA receptors that facilitate excessive calcium influx into the neuronal cells. This leads to the generation of oxidative stress which further leads to mitochondrial dysfunction, lipid peroxidation and oxidation of proteins and DNA. As a consequence, neuronal cell death takes place and ultimately people start facing some serious disabilies. Conclusion: In the present review we provide extensive overview of the role of reactive oxygen species (ROS)-induced oxidative stress and its fatal effects on brain after TBI.

scholarly journals Effects of S-2474, a novel nonsteroidal anti-inflammatory drug, on amyloid β protein-induced neuronal cell death

2001 ◽  
Vol 134 (3) ◽  
pp. 673-681 ◽  
Author(s):  
Tatsurou Yagami ◽  
Keiichi Ueda ◽  
Kenji Asakura ◽  
Toshiyuki Sakaeda ◽  
Takayuki Kuroda ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell Death ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Amyloid Β Protein ◽  
Inflammatory Drug ◽  
Β Protein ◽  
Anti Inflammatory

scholarly journals ATF4 promotes angiogenesis and neuronal cell death and confers ferroptosis in a xCT-dependent manner

Oncogene ◽  
2017 ◽  
Vol 36 (40) ◽  
pp. 5593-5608 ◽  
Author(s):  
D Chen ◽  
Z Fan ◽  
M Rauh ◽  
M Buchfelder ◽  
I Y Eyupoglu ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Dependent Manner

scholarly journals Mesenchymal Stem Cells (MSCs) Coculture Protects [Ca2+]i Orchestrated Oxidant Mediated Damage in Differentiated Neurons In Vitro

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 250 ◽  
Author(s):  
Adel Alhazzani ◽  
Prasanna Rajagopalan ◽  
Zaher Albarqi ◽  
Anantharam Devaraj ◽  
Mohamed Hessian Mohamed ◽  
...  
Keyword(s):  
Cell Death ◽  
Transforming Growth Factor ◽  
Neuronal Cells ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Apoptotic Cells ◽  
Sequence Of Events ◽  
Cox 2 ◽  
Anti Inflammatory

Cell-therapy modalities using mesenchymal stem (MSCs) in experimental strokes are being investigated due to the role of MSCs in neuroprotection and regeneration. It is necessary to know the sequence of events that occur during stress and how MSCs complement the rescue of neuronal cell death mediated by [Ca2+]i and reactive oxygen species (ROS). In the current study, SH-SY5Y-differentiated neuronal cells were subjected to in vitro cerebral ischemia-like stress and were experimentally rescued from cell death using an MSCs/neuronal cell coculture model. Neuronal cell death was characterized by the induction of proinflammatory tumor necrosis factor (TNF)-α, interleukin (IL)-1β and -12, up to 35-fold with corresponding downregulation of anti-inflammatory cytokine transforming growth factor (TGF)-β, IL-6 and -10 by approximately 1 to 7 fold. Increased intracellular calcium [Ca2+]i and ROS clearly reaffirmed oxidative stress-mediated apoptosis, while upregulation of nuclear factor NF-B and cyclo-oxygenase (COX)-2 expressions, along with ~41% accumulation of early and late phase apoptotic cells, confirmed ischemic stress-mediated cell death. Stressed neuronal cells were rescued from death when cocultured with MSCs via increased expression of anti-inflammatory cytokines (TGF-β, 17%; IL-6, 4%; and IL-10, 13%), significantly downregulated NF-B and proinflammatory COX-2 expression. Further accumulation of early and late apoptotic cells was diminished to 23%, while corresponding cell death decreased from 40% to 17%. Low superoxide dismutase 1 (SOD1) expression at the mRNA level was rescued by MSCs coculture, while no significant changes were observed with catalase (CAT) and glutathione peroxidase (GPx). Interestingly, increased serotonin release into the culture supernatant was proportionate to the elevated [Ca2+]i and corresponding ROS, which were later rescued by the MSCs coculture to near normalcy. Taken together, all of these results primarily support MSCs-mediated modulation of stressed neuronal cell survival in vitro.

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