• Proceedings of the PSK Conference
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• 2003.04a
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• pp.197.2-198
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• 2003

Activation of the apoptosis program by an increased production of beta-amyloid peptides (A${\beta}$) has been implicated in the neuronal cell death of Alzheimer's disease. Bcl-2 is a well demonstrated anti-apoptotic protein, however, the mechanism of anti-apoptotic action of Bcl-2 in A${\beta}$-induced apoptosis of neuronal cells is not fully understood. (omitted)

• Journal of Ginseng Research
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• v.34 no.2
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• pp.138-144
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• 2010

Ginseng (Panax ginseng C.A. Meyer) has been shown to have anti-stress effects in animal studies. However, most studies have only managed to detect altered levels of biomarkers or enzymes in blood or tissue, and the actual molecular mechanisms by which ginseng exerts these effects remain unknown. In this study, the anti-oxidative effect of Korean red ginseng (KRG) was examined in human SK-N-SH neuroblastoma cells. Incubation of SK-N-SH cells with the oxidative stressor hydrogen peroxide resulted in significant induction of cell death. In contrast, pre-treatment of cells with KRG decreased cell death significantly. To elucidate underlying mechanisms by which KRG inhibited cell death, the expression of apoptosis-related proteins was examined by Western blot analysis. KRG pre-treatment decreased the expression of the pro-apoptotic gene caspase-3, whereas it increased expression of the anti-apoptotic gene Bcl-2. Consistent with this, immunoblot analysis showed that pre-treatment of the SK-N-SH cells with KRG inhibited expression of the pro-inflammatory gene cyclooxygenase 2 (COX-2). RT-PCR analysis revealed that the repression of COX-2 expression by KRG pre-treatment occurred at the mRNA level. Taken together, our data indicate that KRG can protect against oxidative stress-induced neuronal cell death by repressing genes that mediate apoptosis and inflammation.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.112-112
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• 2001

Oxidative stress plays an important role in the pathological process of neurodegenerative diseases. Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants, some of which may be neurotoxic. Our previous studies showed that 2,2',5,5'-TetracWorobiphenyl (PCB 52) induced apoptotic death in human neuronal SK-N-MC cells, which was demonstrated on gel electrophoresis by visualization of the proteolytic cleavages of $\beta$-catenin and poly (ADP-ribose) polymerase (PARP) and of the production of characteristic ladder patterns of DNA fragmentation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1459-1466
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• 2006

The water extract of Hwansodan has been traditionally used for treatment of ischemic brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of Hwansodan rescues cells from neurodegenerative disease. PC12 pheochromocytoma cells have been used extensively as a model for studying the cellular and molecular mechanisms of neuronal cell damages. Under deprivation of growth factor and ischemic injury, PC12 cells spontaneously undergoes apoptotic cell death. Serum and glucose deprivation markedly decreased the viability of PC12 cells, which was characterized with apparent apoptotic features such as membrane blebbing as well as fragmentation of genomic DNA and nuclei. However, the aqueous extract of Hwansodan significantly reduced serum and glucose deprivation-induced cell death and apoptotic characteristics through reduction of intracellular peroxide generation. Pretreatment of Hwansodan also ingibited the activation of caspase-3, in turn, degradation of ICAD/DFF45 was completely abolished in serum and glucose deprivated cells. Furthermore, pretreatment of Hwansodan obviously increased heme oxygenase 1 (HO-1) expression in PC12 cells. Taken together, the data suggest that the protective effects of Hwansodan against serum and glucose deprivation induced oxidative injuries may be achieved through the scavenging of reactive oxygene species accompanying with HO-1 induction.

• Nutrition Research and Practice
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• v.4 no.6
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• pp.455-461
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• 2010

The tumor microenvironment, particularly sufficient nutrition and oxygen supply, is important for tumor cell survival. Nutrition deprivation causes cancer cell death. Since apoptosis is a major mechanism of neuronal loss, we explored neuronal apoptosis in various microenvironment conditions employing neuroblastoma (NB) cells. To investigate the effects of tumor malignancy and differentiation on apoptosis, the cells were exposed to poor microenvironments characterized as serum-free, low-glucose, and hypoxia. Incubation of the cells in serum-free and low-glucose environments significantly increased apoptosis in less malignant and more differentiated N-type IMR32 cells, whereas more malignant and less differentiated I-type BE(2)C cells were not affected by those treatments. In contrast, hypoxia (1 % $O_2$) did not affect apoptosis despite cell malignancy. It is suggested that DLK1 constitutes an important stem cell pathway for regulating self-renewal, clonogenicity, and tumorigenicity. This raises questions about the role of DLK1 in the cellular resistance of cancer cells under poor microenvironments, which cancer cells normally encounter. In the present study, DLK1 overexpression resulted in marked protection from apoptosis induced by nutrient deprivation. This in vitro model demonstrated that increasing severity of nutrition deprivation and knock-down of DLK1 caused greater apoptotic death, which could be a useful strategy for targeted therapies in fighting NB as well as for evaluating how nutrient deprived cells respond to therapeutic manipulation.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.4
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• pp.231-238
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• 2005

Neuronal apoptotic events, which result in cell death, are occurred in hypoxic/ischemic conditions. Estradiol is a female sex hormone with steroid structure known to provide neuroprotection through multiple mechanisms in the central nervous system. This study was aimed to investigate the signal transduction pathway of $CoCl_2$-induced neuronal cell death and the inhibitory effects of estradiol. Administration of $CoCl_2$ decreased cell viability in both a dose- and time-dependent manner in PC12 cells. $CoCl_2$-induced cell death produced genomic DNA fragmentation and morphologic changes such as cell shrinkage and condensed nuclei. It was found that $CoCl_2$-treated cells increased the reactive oxygen species (ROS) as well as caspase-8, -9 and -3 activities. However, pretreatment with estradiol before exposure to $CoCl_2$ prevented the reduction in cell viability reduction and attenuated DNA fragmentation and morphologic changes caused by $CoCl_2$. Furthermore, the $CoCl_2$-induced increases of ROS levels and caspases activities were attenuated by estradiol. Gene expression analysis revealed that estradiol blocked the underexpression of the Bcl-2 and ameliorated the increase in the release of cytochrome c from mitochondria into cytoplasm and Fas-ligand (Fas-L) upregulated by $CoCl_2$. These results suggest that $CoCl_2$ induce apoptosis in PC12 cells through both mitochondria- and death receptor-mediated cell death pathway. Estradiol was found to have a neuroprotective effect against $CoCl_2$-induced apoptosis through the inhibition of ROS production and by modulating apoptotic effectors associated with the mitochondria- and death-dependent pathway in PC12 cells.

• Exercise Science
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• v.21 no.3
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• pp.289-298
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• 2012

In the present study, we investigated the effect of treadmill exercise on apoptotic neuronal cell death in the retinas of streptozotocin-induced diabetic rats. Twenty-eight male Sprague-Dawley rats were used for this study. The animals were divided into four groups(n = 7 in each group):(1) control group, (2) exercise group, (3) diabetes-induced group, (4) diabetes-induced and exercise group. Diabetes mellitus(DM) was induced by intraperitoneal injection of streptozotocin. The rats in the exercise groups were forced to run on the treadmill for 30 minutes once a day, five times per a week, during 12 weeks. In this study, a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) assay and western blot for the expressions of caspase-3, cytochrome c, Bax, and Bcl-2 in the retinas were conducted for the detection of apoptotic retinal cell death. The present results showed that the number of TUNEL-positive cells was increased in the retinas of the diabetic rats, whereas treadmill exercise suppressed this number. The expressions of pro-apoptotic factors caspase-3, cytochrome c, and Bax were enhanced and the expressions of anti-apoptotic factor Bcl-2 was decreased in the retinas of the diabetic rats. In contrast, treadmill exercise suppressed the expressions of caspase-3, cytochrome c, and Bax and increased the expression of Bcl-2. The present study demonstrated that treadmill exercise suppressed diabetes-induced apoptotic neuronal cell death in the retinas. Based on the present results, treadmill exercise may be effective therapeutic strategy for the alleviating complications of diabetes patients.

• Food Science and Biotechnology
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• v.15 no.2
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• pp.244-247
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• 2006

Neuronal cell death significantly contributes to neuronal loss in neurological injury and disease. Typically, neuronal loss or destruction upon exposure to neurotoxins, oxidative stress, or DNA damage causes neurodegenerative diseases such as Alzheimer's disease. In this study, we attempted to determine whether ginsenoside Rg3 from red ginseng has a neuroprotective effect via an anti-apoptotic role induced by S-nitroso-N-acetylpenicillamine (SNAP) at the molecular level. We also investigated the antioxidant effect of Rg3 using a metal-catalyzed reaction with $Cu^{2+}/H_2O_2$. Our results showed that Rg3 ($40-100\;{\mu}g/mL$) protected SK-N-MC neuroblastoma cells under cytotoxic conditions and effectively protected DNA from fragmentation. In the signal pathway, caspase-3, and poly (ADP-ribose) polymerase (PARP) were kept at an inactivated status when pretreated with Rg3 in all ranges. In particular, the important upstream p-Akt signal pathway was increased in a dose-dependent manner, which indicates that Rg3 may contribute to cell survival. We also found that oxidative stress can be mitigated by Rg3. Therefore, we have concluded that Rg3 plays a certain role in neurodegenerative pathogenesis via an anti apoptotic, antioxidative effect.

• Korean Journal of Oriental Medicine
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• v.8 no.1
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• pp.109-126
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• 2002

The herbal extract (YMT_02) is a modified herbal extracts from Yukmijihwangtang (YMJ) to promote memory-enhancing. The YMJ extracts has been widely used as an anti-aging herbal medicine for hundred years in Asian countries. The purpose of this study is to; 1) quantitatively evaluate the memory-enhancing effect of YMT_02 by hehavior task, 2) identify candidate genes responsible for enhancing memory by cDNA microarray and 3) assess the anti-oxidant effect of YMT_02 on PC12 cell. Memory retention abilities are addressed by passive avoidance task with Sprague-Dawley (SD) male rat. Before the training session, the rats are subdivided into four groups and administrated with YMT_02, Ginkgo biloba, Soya lecithin and normal saline for 10 days. The retention test was performed. 24 hours after the training session. The retention time of the YMT_02 group was significantly (p<0.05) delayed $({\sim}100%)$, whereas Ginkgo biloba and Soya lecithin treatment delayed 20% and 10% respectively. The hippocampi of YMT_02 and control group were dissected and mRNA was further purified. After synthesizing cDNA using oligo-dT primer, the cDNA were applied and mRNA was further purified. After synthesizing cDNA using oligo-dT primer, the cDNA were applied to Incyte rat GEMTM 2 cDNA microarray. The microarray results show that prealbumin(transthyretin), phosphotidy lethanolamine N-methyltransferase, and PEP-19 are expressed abundantly in the YMT_02 treated group. Especially, PEP-19 is a neuron-specific protein, which inhibits apoptotic processes in neuronal cell. On the other hand, transcripts of RAB15, glutamate receptor subunit 2 and CDK 108 are abundant in control group. Besides, neuronal genes involved in neuronal death or neurodegeneration such as neuronal-pentraxin and spectrin are abundantly expressed in control group. Additionally, the YMT_02 shows an anti oxidative effect in the PC12 cell. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the memory-enhancing effect of herbal extracts YMT_02, for example, anti-apoptotic, anti-oxidative, and neuroprotective effects.

• The Korean Journal of Food And Nutrition
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• v.30 no.6
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• pp.1279-1285
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• 2017

$Amyloid-{\beta}$ protein ($A{\beta}$) is known to increase free radical production in neuronal cells, leading to cell death by oxidative stress. The purpose of this study was to evaluate the protective effects of $PineXol^{(R)}$ on $A{\beta}_{25-35}$ induced neuronal cell death. Rat pheochromocytoma (PC-12) cells were pre-treated with $100{\mu}g/mL$ of $PineXol^{(R)}$ for 2 h. The cells were exposed to single dose of $30{\mu}M$ $A{\beta}_{25-35}$ for 24 h. Cell death was assessed by a cell count kit-8 (CCK-8) assay, lactate and dehydrogenase (LDH) release assay. An Apoptotic process was analyzed by a protein expression of the Bcl-2 family using western blotting. Cell viability increased in PC-12 cells treated with both $A{\beta}_{25-35}$ and $PineXol^{(R)}$, compared to the control group. $PineXol^{(R)}$ induced a decrease of the Bcl-2 protein expression (p<0.05), while Bax and Sod1 increased (p<0.05), indicating attenuation of $A{\beta}_{25-35}$ induced apoptosis. These results suggest that $PineXol^{(R)}$ may be a good candidate for the prevention of Alzheimer's disease(AD).