• Korean Journal of Veterinary Research
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• v.54 no.1
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• pp.1-6
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• 2014

Parkinson's disease is known to exhibit progressive degeneration of the dopaminergic neurons in the substantia nigra via inhibition of glutathione metabolism. It is well known that 6-Hydroxydopamine (6-OHDA) induces Parkinson's disease-like symptoms, while resveratrol (3,5,4'-trihydroxystilbene) has been shown to have anti-inflammatory and antioxidant effects. In the present study, we investigated the neuroprotective effects of resveratrol, a phytoalexin found in grapes and various plants, on 6-OHDA-induced cell damage to the SH-SY5Y human neuroblastoma cell line. Resveratrol (5 and 10 ${\mu}M$) inhibited 6-OHDA (60 ${\mu}M$)-induced cytotoxicity in SH-SY5Y cells and induced a reduction of the number of apoptotic nuclei caused by 6-OHDA treatment. Additionally, the total apoptotic rate of cells treated with both resveratrol (10 ${\mu}M$) and 6-OHDA (60 ${\mu}M$) was less than that of 6-OHDA treated cells. Resveratrol also dose-dependently (1, 5 and 10 ${\mu}M$) scavenged reactive oxygen species (ROS) induced by 6-OHDA in SH-SY5Y cells and prevented depletion of glutathione in response to the 6-OHDA-induced cytotoxicity in the glutathione assay. Overall, these results indicate that resveratrol exerts a neuroprotective effect against 6-OHDA-induced cytotoxicity of SH-SY5Y cells by scavenging ROS and preserving glutathione.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.6
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• pp.281-286
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• 2002

To understand the cytotoxic mechanism of $MPP^+,$ we examined the involvement of ceramide in $MPP^+-induced$ cytotoxicity to human neuroblastoma SH-SY5Y cells. When SH-SY5Y cells were exposed to $MPP^+,\;MPP^+$ induced dose-dependent cytotoxicity accompanied by 2-fold elevation of intracellular ceramide levels in SH-SY5Y cells. Three methods were used to test the hypothesis that the elevated intracellular ceramide is related to $MPP^+-induced$ cytotoxicity: $C_2-ceramide$ was directly applied to cells, sphingomyelinase (SMase) was exogenously added, and oleoylethanolamine (OE) was used to inhibit degradation of ceramide. Furthermore, inhibition of ceramide-activated protein phosphatase (CAPP), the effector of ceramide, using okadaic acid (OA) attenuated cell death but treatment of fumonisin $B_1,$ the ceramide synthase inhibitor, did not alter the cytotoxic effect of $MPP^+.$ Based on these, we suggest that the elevation of intracellular ceramide is one of the important mediators in $MPP^+-induced$ cell death.

• Molecules and Cells
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• v.39 no.2
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• pp.119-128
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• 2016

Angelica polymorpha Maxim root extract (APRE) is a popular herbal medicine used for treating stomachache, abdominal pain, stomach ulcers, and rheumatism; however the effect of APRE on cancer cells has not yet been explored. Here, we examined APRE cytotoxicity seen on target neuroblastoma cells (NB) using cell viability assays, DAPI visualization of fragmented DNA, and Western blotting analysis of candidate signaling pathways involved in proliferation and apoptosis. We demonstrated that APRE reduced cell viability in NB to a greater extent than in fibroblast cells. In addition, we found that APRE could inhibit the three classes of MAPK proteins and could also down-regulate the PI3K/AKT/GSK-$3{\beta}$ activity all being relevant for proliferation and survival. APRE could also up-regulate Bax expression and down-regulate Bcl-2 and Mcl-1. With APRE treatment, depolarization of mitochondria membrane potential and activation of caspase-3 was demonstrated in the SH-SY5Y cells. We could not found increased activity of death receptor and caspase-8 as markers of the extrinsic apoptosis pathway for the APRE treated cells. In presence of a caspase-3 siRNA and a pan-caspase inhibitor, APRE could not reduce the viability of NB cells to a significant degree. So we predicted that with APRE, the intrinsic pathway was solely responsible for inducing apoptosis as we also showed that the non-caspase autophagy pathway or ER stress-ROS mediated pathways were not involved. These findings demonstrate that an intrinsic mitochondria-mediated apoptosis pathway mediates the apoptotic effects of APRE on SH-SY5Y cells, and that APRE shows promise as a novel agent for neuroblastoma therapy.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2021.04a
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• pp.58-58
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• 2021

Although hypoxic/ischemic injury is thought to contribute to the incidence of Alzheimer disease (AD), the molecular mechanism that determines the relationship between hypoxia-induced β-amyloid (Aβ) generation and development of AD is not yet known. In this study, we investigated the protective effects of Acorus gramineus Soland. (AGS) on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced A β production in SH-SY5Y human neuroblastoma cells. Pretreatment of these cells with AGS significantly attenuated OGD/R-induced production of reactive oxygen species (ROS) and elevation of levels of malondialdehyde, nitrite (NO), prostaglandin E2 (PGE2), cytokines (TNF-α, IL-1β and IL-6) and glutathione, as well as superoxide dismutase activity. AGS also reduced OGD/R-induced expression of the apoptotic protein caspase-3, the apoptosis regulator Bcl-2, and the autophagy protein becn-1. Finally, AGS reduced OGD/R-induced Aβ production and cleavage of amyloid precursor protein, by inhibiting secretase activity and suppressing the autophagic pathway. Although supporting data from in vivo studies are required, our results indicate that AGS may prevent neuronal cell damage from OGD/R-induced toxicity.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.5
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• pp.163-169
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• 2007

The neurotoxicity of amyloid $\beta(A\beta)$ is associated with an increased production of reactive oxygen species and apoptosis, and it has been implicated in the development of Alzheimer's disease. While(-)-epigallocatechin-3-gallate(EGCG) suppresses $A\beta$-induced apoptosis, the mechanisms underlying this process have yet to be completely clarified. This study was designed to investigate whether EGCG plays a neuroprotective role by activating cell survival system such as protein kinase C(PKC), extracellular-signal-related kinase(ERK), c-Jun N-terminal kinase(JNK), and anti-apoptotic and pro-apoptotic genes in SH-SY5Y human neuroblastoma cells. One ${\mu}M\;A{\beta}_{1-42}$ decreased cell viability, which was correlated with increased DNA fragmentation evidenced by DAPI staining. Pre-treatment of SH-SY5Y neuroblastoma cells with EGCG($1{\mu}M$) significantly attenuated $A{\beta}_{1-42}$-induced cytotoxicity. Potential cell signaling candidates involved in this neuroprotective effects were further examined. EGCG restored the reduced PKC, ERK, and JNK activities caused by $A{\beta}_{1-42}$ toxicity. In addition, gene expression analysis revealed that EGCG prevented both the $A{\beta}_{1-42}$-induced expression of a pro-apoptotic gene mRNA, Bad and Bax, and the decrease of an anti-apoptotic gene mRNA, Bcl-2 and Bcl-xl. These results suggest that the neuroprotective mechanism of EGCG against $A{\beta}_{1-42}$-induced apoptotic cell death includes stimulation of PKC, ERK, and JNK, and modulation of cell survival and death genes.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2000.12a
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• pp.48-48
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• 2000

• Proceedings of the Zoological Society Korea Conference
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• 1996.10a
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• pp.147.1-147
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• 1996

No Abstract, See Full Text

• BMB Reports
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• v.46 no.5
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• pp.276-281
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• 2013

In this study, we aimed to compare the morphogenetic and neuronal characteristics between monolayer cells and spheroids. For this purpose, we established spheroid formation by growing SH-SY5Y cells on the hydrophobic surfaces of thermally-collapsed elastin-like polypeptide. After 4 days of culture, the relative proliferation of the cells within spheroids was approximately 92% of the values for monolayer cultures. As measured by quantitative assays for mRNA and protein expressions, the production of synaptophysin and neuronspecific enolase (NSE) as well as the contents of cell adhesion molecules (CAMs) and extracellular matrix (ECM) proteins are much higher in spheroids than in monolayer cells. Under the all-trans-retinoic acid (RA)-induced differentiation condition, spheroids extended neurites and further up-regulated the expression of synaptophysin, NSE, CAMs, and ECM proteins. Our data indicate that RA-differentiated SH-SY5Y neurospheroids are functionally matured neuronal architectures.

• Molecular & Cellular Toxicology
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• v.4 no.2
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• pp.164-169
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• 2008

Methylmercury (MeHg) is known to have devastating effects on the mammalian nervous system. In order to characterize the mechanism of MeHg-induced neurotoxicity, we investigated the analysis of transcriptional profiles on human 8k cDNA microarray by treatment of $1.4{\mu}M$ MeHg at 3, 12, 24 and 48h in human neuroblastoma SH-SY5Y cell line. Some of the identified genes by MeHg treatment were significant at early time points (3h), while that of others was at late time points (48h). The early response genes that may represent those involved directly in the MeHg response included pantothenate kinase 3, a kinase (PRKA) anchor protein (yotiao) 9, neurotrophic tyrosine kinase, receptor, type 2 gene, associated with NMDA receptor activity regulation or perturbations of central nervous system homeostasis. Also, when SH-SY5Y cells were subjected to a longer exposure (48h), a relative increase was noted in a gene, glutamine-fructose-6-phosphate transaminase 1, reported that overexpression of this gene may lead to the increased resistance to MeHg. To confirm the alteration of these genes in cultured neurons, we then applied real time-RT PCR with SYBR green. Thus, this result suggests that a neurotoxic effect of the MeHg might be ascribed that MeHg alters neuronal receptor regulation or homeostasis of neuronal cells in the early phase. However, in the late phase, it protects cells from neurotoxic effects of MeHg.

• Archives of Pharmacal Research
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• v.28 no.2
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• pp.216-219
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• 2005

Wogonin (5,7-dihydroxy-8-methoxyflavone) has been reported to exhibit a variety of biological properties including anti-inflammatory and neuroprotective functions. In this study, biological activities of diverse synthetic wogonin derivatives have been evaluated in two experimental cell culture models. Inhibitory activities of wogonin derivatives on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglial cells and on hydrogen peroxide ($H_{2}O_2$)-induced neuronal cell death in SH-SY5Y human neuroblastoma were examined. Wogonin derivatives such as WS2 and WS3 showed more potent suppressive activities on LPS-induced NO production and $H_{2}O_2$-induced cytotoxicity than wogonin itself. In addition, thiol substitution played a minor role in enhancing the activities of the derivatives. These findings may contribute to the development of novel anti-inflammatory and neuroprotective agents derived from wogonin.