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ABSTRACT: In the brain, Na+/H+ exchanger-1 (NHE-1) activation has a significant impact on ischemic injury, and, in recent studies, NHE-1 inhibition has been found to protect neurons from ischemic injury. This protective effect has been ascribed to the prevention of apoptosis, but neuronal cell death following ischemia is a consequence of both necrotic and apoptotic cell death. Here, we evaluated the ability of the potent NHE-1 inhibitor cariporide to prevent necrotic cell death in an in vitro model of excitotoxic neuronal death. Cariporide (100 nM) was found to reduce both glutamate-induced necrotic and apoptotic neuronal cell death. Ca2+ concentrations were observed to peak twice in cytosol and mitochondria in cultured neuronal cells after glutamate exposure, and cariporide was found to reduce the second Ca2+ concentration increase, but not the first. Furthermore, glutamate-mediated mitochondrial death pathways involving loss of mitochondrial membrane potential and reactive oxygen species (ROS) accumulation were found to be attenuated by cariporide. In addition, cariporide effectively prevented necrosis following exposure to glutamate and ameliorated the mitochondrial Ca2+ and ROS production increases implicated in necrotic cell death. These results suggest that NHE-1 participates in the necrotic cell death process and that its inhibition offers a means of preventing both necrosis and apoptosis.
Journal of Neuroscience Research 04/2012; 90(4):860-9. · 2.74 Impact Factor
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ABSTRACT: Grape seed extract (GSE) is a potent antioxidant. We examined the effect of GSE on oxidative stress-induced cell death in a transformed retinal ganglion cell line, RGC-5.
Staurosporine-differentiated RGC-5 (ssdRGC-5) cells obtained by treating RGC-5 cells with 1 µM staurosporine were incubated with GSE for 2 h and then exposed to buthionine sulfoximine plus glutamate (B/G) for 24 h. Cell death was detected using the LIVE/DEAD viability assay and the type of cell death was evaluated using fluorescein isothiocyanate-conjugated Annexin-V/propidium iodide staining. To investigate the mechanism underlying cell death, we determined the caspase-3 activity and level of reactive oxygen species (ROS) formation.
Treatment of ssdRGC-5 cells with B/G increased intracellular ROS and induced apoptosis (not necrosis) with increasing caspase-3 activity. GSE rescued the ssdRGC-5 cells from oxidative stress-induced cell death by inhibiting both intracellular ROS production and caspase-3 activation.
GSE had a neuroprotective effect against oxidative stress-induced apoptotic death in ssdRGC-5 cells.
Current eye research 04/2012; 37(4):339-44. · 1.51 Impact Factor
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ABSTRACT: Acrylamide is formed during cooking processes and is present in many foods. Accumulating evidence suggests that AA is carcinogenic, but the underlying mechanism remains unclear. Here, we investigated the carcinogenesis mechanisms of AA. AA increased the COX-2 expression. Two major transcription factors, AP-1 and NF-κB, were activated by AA treatment. AA induced the ERK phosphorylation, and this was abolished by the treatment of U0126, a pharmacological inhibitor of MEK, an upstream kinase of ERK. AA-induced expression and promoter activity of COX-2 were suppressed by U0126. U0126 treatment attenuated AA-induced transactivation of AP-1 and NF-κB, suggesting that the MEK/ERK signaling pathway regulates COX-2 expression. In addition, myricetin, a natural inhibitor of the MEK/ERK signal pathway, reduced AA-induced activation of the COX-2 promoter as well as activation of AP-1 and NF-κB. Collectively, these results suggest that the ability of AA to up-regulate COX-2 expression through the MEK/ERK signaling pathway underlies AA carcinogenicity.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 03/2011; 49(6):1249-54. · 2.99 Impact Factor
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ABSTRACT: The present study was performed to evaluate the effects of two different phenolic antioxidants, resveratrol (3,5,4'-trihydroxystilbene) and butylated hydroxyanisole (BHA), on the hydrogen peroxide (H2O2)-induced inhibition of gap-junction intercellular communication (GJIC) in WB-F344 rat liver epithelial cells (WB-F344). Resveratrol is a naturally occurring polyphenolic antioxidant; on the other hand, BHA is a synthetic phenolic compound. We found that only resveratrol protects WB-F344 cells from H2O2-induced inhibition of GJIC, and BHA has no effect. The extracellular-signal-regulated protein kinase 1/2 (ERK1/2)-connexin 43 (Cx43) signaling pathway is crucial for the regulation of GJIC in rat liver epithelial cells, and resveratrol, but not BHA, blocked the H2O2-induced phosphorylation of Cx43, a critical regulator of GJIC, and ERK1/2 in WB-F344 cells. Resveratrol appears to attenuate the H2O2-mediated ERK1/2-Cx43 signaling pathway and consequently reverses H2O2-mediated inhibition of GJIC. DPPH and ABTS radical-scavenging assays revealed that the protective effect of resveratrol on the H2O2-mediated inhibition of GJIC was not mediated through its free radical-scavenging activity.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 09/2009; 671(1-2):40-4. · 2.85 Impact Factor
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ABSTRACT: Cocoa, a good source of dietary antioxidative polyphenols, exhibited anticarcinogenic activity in animal models, but the molecular mechanisms of the chemopreventive potential of cocoa remain unclear. Inhibition of gap-junction intercellular communication (GJIC) is strongly related to tumorigenesis. Cocoa polyphenol extracts (CPE) dose dependently attenuated hydrogen peroxide (H(2)O(2))-induced inhibition of GJIC in rat liver epithelial (RLE) cells. CPE inhibited the H(2)O(2)-induced phosphorylation and internalization of connexin 43, which is a regulating protein of GJIC in RLE cells. The H(2)O(2)-induced accumulation of reactive oxygen species and activation of extracellular signal-regulated kinase were inhibited by CPE treatment. However, CPE did not block H(2)O(2)-induced phosphorylation of p38 mitogen-activated protein kinase. An ex vivo kinase assay demonstrated that CPE inhibited the H(2)O(2)-induced mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) 1 activity in RLE cell lysates. Ex vivo pull-down assay data revealed that CPE directly bound with MEK1 to inhibit MEK1 activity. These results indicate that CPE protects against the H(2)O(2)-induced inhibition of GJIC through antioxidant activity and direct inhibition of MEK activity, which may contribute to its chemopreventive potential.
The Journal of nutritional biochemistry 08/2009; 21(8):680-6. · 4.29 Impact Factor
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Bo Kyung Lee,
Dong Ha Lee,
Sok Park,
Sung Lyea Park,
Jae-Seok Yoon,
Min Goo Lee,
Sunkyung Lee,
Kyu Yang Yi,
Sung Eun Yoo,
Kyung Hee Lee,
You-Sun Kim,
Soo Hwan Lee,
Eun Joo Baik,
Chang-Hyun Moon,
Yi-Sook Jung
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ABSTRACT: We investigated the effects of a novel Na(+)/H(+) exchanger-1 (NHE-1) inhibitor KR-33028 on glutamate excitotoxicity in cultured neuron cells in vitro and cerebral infarct in vivo by comparing its potency with that of zoniporide, a well-known, highly potent NHE-1 inhibitor. KR-33028 inhibited NHE-1 activation in a concentration-dependent manner (IC(50)=2.2 nM), with 18-fold greater potency than that of zoniporide (IC(50)=40.7 nM). KR-33028 significantly attenuated glutamate-induced LDH release with approximately 100 times lower EC(25) than that of zoniporide in cortical neurons in vitro (EC(25) of 0.007 and 0.81 microM, respectively), suggesting its 100-fold greater potency than zoniporide in producing anti-necrotic effect. In addition, the EC(50) of KR-33028 for anti-apoptotic effect was 100 times lower than that of zoniporide shown by TUNEL positivity (0.005 and 0.62 microM, respectively) and caspase-3 activity (0.01 and 2.64 microM, respectively). Furthermore, the EC(50) value of KR-33028 against glutamate-induced intracellular Ca(2+) overload was also 100 times lower than that of zoniporide (EC(50) of 0.004 and 0.65 microM, respectively). In the in vivo cerebral infarct model (60 min middle cerebral artery occlusion followed by 24 h reperfusion), KR-33028 reduced infarct size in a dose-dependent manner. Its ED(25) value, however, was quite similar to that of zoniporide (ED(25) of 0.072 and 0.097 mg/kg, respectively). Hence these results suggest that the novel NHE-1 inhibitor, KR-33028, could be an efficient therapeutic tool to protect neuronal cells against ischemic injury.
Brain research 12/2008; 1248:22-30. · 2.46 Impact Factor
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ABSTRACT: The red tide of dinoflagellate, Cochlodinium polykrikoides has frequently occurred in coastal waters, causing severe damage to fisheries. In the present study, the algicidal bacterium Alteromonas sp. A14 isolated from the southern coast of Korea was applied to a red tide of C. polykrikoides in a laboratory experiment. In the experiment, the abundance of the strain A14 was monitored using fluorescence in situ hybridization. Inoculation of the A14 at a final cell density of 9.0 x 10(5) cells/ml caused a significant decrease in C. polykrikoides abundance from 1,830 to 700 cells/ml during 2 days, while abundances of harmless diatoms rapidly increased from 3 days. Abundances of both A14 and other bacteria increased to 1 day. After 1 day, with flagellate abundance increased, bacterial abundance decreased. Finally, algicidal bacterial abundance decreased to 3.5 x 10(4) cells/ml. In the biological control of harmful algal blooms, in addition to decrease in target algal abundance and not occurrence of other harmful blooms, decrease in abundance of utilized organism is also important. This study emphasizes the importance of monitoring the inoculated bacterium when applying bacterium to natural seawater.
The Journal of Microbiology 07/2008; 46(3):274-82. · 1.10 Impact Factor
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ABSTRACT: Propyl gallate and its metabolite, gallic acid, are widely used as antioxidants in the food industry, but they have been shown to exhibit liver toxicity and enhance carcinogenesis. In the present study, we investigated the possible undesirable effects of propyl gallate and gallic acid on gap junctional intercellular communication (GJIC), inhibition of which is closely linked to carcinogenesis. Gallic acid and propyl gallate exhibited dose-dependent free-radical-scavenging activities as determined by 1,1-diphenyl-2-picrylhydrazyl- or 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)-radical-scavenging assays, and the free-radical-scavenging activity of gallic acid was stronger than that of propyl gallate. However, using WB-F344 rat liver epithelial cells, gallic acid inhibited GJIC in a dose-dependent manner, while propyl gallate had no significant effect compared with untreated controls. The gallic-acid-induced inhibition of GJIC was reversible, with a recovery of nearly 65% after 120 min. Gallic acid induced the phosphorylation of connexin 43 (Cx43) and phosphorylation of extracellular-signal-regulated kinase1/2 (ERK1/2). The gallic-acid-induced inhibition of GJIC was attenuated by treatment with mitogen-activated protein kinase kinase inhibitors (U0126 and PD098059). U0126 blocked the gallic-acid-induced phosphorylation of Cx43 and ERK1/2, indicating that the gallic-acid-induced inhibition of GJIC is mediated by phosphorylation of Cx43 via activation of ERK1/2. In addition, gallic-acid-induced inhibition of GJIC was protected by ascorbic acid and quercetin, which might represent a simple example of the different effects of natural antioxidants in carcinogenesis.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 03/2008; 638(1-2):175-83. · 2.85 Impact Factor
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ABSTRACT: The purpose of this study was to characterize the putative anxiolytic-like effects of the aqueous extract of hooks with stem of Uncaria rhynchophylla using the elevated plus maze (EPM) and the hole-board apparatus in rats and mice. Control rats were treated with an equal volume of saline, and positive control rats with buspirone (1 mg/kg). Single or repeated treatments of the aqueous extract of Uncaria rhynchophylla (200 mg/kg/day, p.o.) for 7 days significantly increased the time-spent and entries into open arms of the EPM, and reduced the time-spent and entries into the closed arms versus saline controls (P<0.05). However, no changes in spontaneous locomotor activity or myorelaxant effects were observed versus saline controls. In the hole-board test, repeated treatment with the aqueous extract of Uncaria rhynchophylla (100 or 200 mg/kg/day, p.o.) significantly increased the number of head-dips (P<0.05). In addition, the anxiolytic-like effects of Uncaria rhynchophylla extract as assessed using the EPM test were abolished by WAY 100635 (0.3 mg/kg, i.p.), a 5-HT(1A) receptor antagonist. These results suggest that Uncaria rhynchophylla is an effective anxiolytic agent, and acts via the serotonergic nervous system.
Journal of Ethnopharmacology 12/2006; 108(2):193-7. · 3.01 Impact Factor
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Hye-Seong Park, Bo Kyung Lee,
Sok Park,
Seung U Kim,
Soo Hwan Lee,
Eun Joo Baik,
Sunkyung Lee,
Kyu Yang Yi,
Sung Eun Yoo,
Chang-Hyun Moon,
Yi-Sook Jung
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ABSTRACT: We investigated the effects of an Na(+)/H(+) exchanger inhibitor, sabiporide, on excitotoxicity in cultured neuronal cells and in vivo. Sabiporide attenuated glutamate- or NMDA (N-methyl-d-aspartic acid)-induced neuronal cell death. Sabiporide also reduced glutamate or NMDA-induced increase in [Ca(2+)](i). In in vivo brain ischemia model, sabiporide produced protective effects, decreasing the infarct size and edema volume. Our results suggest that sabiporide elicits neuroprotective effect both in vitro and in vivo.
Brain Research 12/2005; 1061(1):67-71. · 2.73 Impact Factor
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ABSTRACT: We investigated the role of individual protein kinase C (PKC) isoforms during kainate toxicity in cortical neurons. Treatment with 50 microM kainate induced isoform-specific activation of PKC-delta according to the translocation from the soluble to the particulate fraction, while it caused remarkable decreases in PKC alpha, beta, epsilon and zeta in both fractions. Kainate-induced neuronal death was significantly increased by pharmacological inhibition of PKC-delta with rottlerin, suggesting a protective role of PKC-delta against kainate toxicity. A PKC activator phorbol 12-myristate 13-acetate remarkably attenuated the kainate-induced neuronal death. Although phorbol 12-myristate 13-acetate activates PKC-epsilon and PKC-delta, the protective effect of phorbol 12-myristate 13-acetate was almost completely abolished by rottlerin, but not by epsilonV1-2. These results suggest that activation of PKC-delta attenuates the kainate-induced cell death of cortical neurons.
Neuroreport 06/2005; 16(7):741-4. · 1.66 Impact Factor
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ABSTRACT: Myristicin, 1-allyl-3,4-methylenedioxy-5-methoxybenzene, is a naturally occurring alkenylbenzene compound found in the nutmeg. The present study was conducted to assess the cytotoxic and apoptotic effects of myristicin on the human neuroblastoma SK-N-SH cells. We found that a dose-dependent reduction in cell viability occurs at myristicin concentration > or =0.5 mM in SK-N-SH cells. Apoptotic cell death was confirmed using DNA fragmentation, terminal deoxyribonucelotidyl transferase-mediated dUTP nick end labeling and by 4,6-diamidino-2-phenylindole staining. Microscopy was used to observe apoptotic cell morphology. Western blotting was used to investigate the protein expression of known apoptotic mediators including cytochrome c, caspase-3, and PARP. The apoptosis triggered by myristicin was accompanied by an accumulation of cytochrome c and by the activation of caspase-3. The results obtained suggest that myristicin induces cytotoxicity in human neuroblastoma SK-N-SH cells by an apoptotic mechanism. This myristicin-induced apoptosis provides further insight of the molecular mechanisms of myristicin toxicity.
Toxicology Letters 05/2005; 157(1):49-56. · 3.23 Impact Factor
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ABSTRACT: The purpose of the this study was to characterize the putative anxiolytic-like effects of the aqueous extract of Albizzia julibrissin stem bark using the elevated plus maze (EPM) in rats. The water extract of Albizzia julibrissin was orally administered at 10, 50, 100 or 200 mg/kg to adult male SD rats, 1 h before behavioral evaluation in an EPM, respectively. Control rats were treated with an equal volume of saline, and positive control rats buspirone (1 mg/kg). Single or repeated treatment (for 7 days) of the water extract of Albizzia julibrissin (at 100 or 200 mg/kg) significantly increased time-spent and arm entries into the open arms of the EPM, and decreased time-spent and arm entries in the closed arms of the EPM versus saline controls (P < 0.05). However, no changes in the locomotor activity and myorelaxant effect were seen in any group versus the saline control. In addition, the anxiolytic-like effects of Albizzia julibrissin extract were abolished by pindolol (10 mg/kg, i.p), a 5-HT(1A/1B) receptor antagonist. These results suggest that Albizzia julibrissin might proved to be an effective anxiolytic agent, and that it acts via the serotonergic nervous system.
Life Sciences 10/2004; 75(23):2787-95. · 2.53 Impact Factor
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ABSTRACT: We investigated which isoforms of PKCs can be modulated and what their roles are during l-buthionine-S,R-sulfoximine (BSO)-induced neuronal death. We observed the isoform specific translocation of PKC-epsilon from the soluble fraction to the particulate in cortical neurons treated with 10 mM BSO. The translocation of PKC-epsilon by BSO was blocked by antioxidant trolox, suggesting the PKC-epsilon as a downstream of reactive oxygen species (ROS) elevated by BSO. Trolox inhibited the ROS elevation and the neuronal death in BSO-treated cortical cells. The BSO-induced neuronal death was remarkably inhibited by both the pharmacological inhibition of PKC-epsilon with epsilonV1-2 and the functional blockade for PKC-epsilon through overexpression of PKC-epsilon V1 region, suggesting the detrimental role of PKC-epsilon. These results suggest that PKC-epsilon is the major PKC isoform involved in the pathways triggered by ROS, leading to neuronal death in BSO-treated cortical neurons.
Biochemical and Biophysical Research Communications 08/2004; 320(3):789-94. · 2.48 Impact Factor
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Wireless Communications and Mobile Computing. 01/2004; 4:233-245.
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ABSTRACT: The IETF mobile IPv6 (MIPv6) enables correspondent nodes (CNs) to directly send packets to a mobile node (MN) using care-of address of the MN. For this service, however, MNs always have to inform CNs and the home agent (HA) of its new location at each movement. To reduce this control signaling, the existing hierarchical scheme built on top of the MIPv6 separates micro-mobility from macro-mobility and exploit an MN's locality. However, the hierarchical scheme does not achieve real optimization of packet routing. Packets from CN to MN are delivered through an intermediate mobility agent. It brings needless delay on packet delivery and imposes heavy loads on the intermediate mobility agent. In this paper, we propose a new hierarchical scheme that enables any CNs to send packets to an MN without helps of the intermediate mobility agent using a subnet residence time in the profile. This proposal can reduce delay in packet delivery and optimize packet delivery routing. Furthermore, it can alleviate heavy loads on the intermediate mobility agent.
Vehicular Technology Conference, 2003. VTC 2003-Spring. The 57th IEEE Semiannual; 05/2003
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ABSTRACT: Many dynamic location update schemes such as time-based, movement-based, and distance-based; have been studied in the location management of mobile communication. Also there are many studies that improve these schemes adaptively using mobile nodes' call and mobility patterns. These schemes usually use the prediction-based algorithms for mobile nodes' mobility patterns. However those need complicated computation such as heuristic algorithm. Those schemes' management cost are various for mobile nodes' diverse mobility patterns. In this paper we propose a novel approach in which the location management costs are rarely affected by mobile nodes' mobility patterns. The basic idea is to use the velocity of a mobile node, which is represented by the combination of two thresholds: time threshold T and distance threshold D. The update process is triggered by the change of mobile nodes' velocity, that is two thresholds. These values are adjusted by simple algorithm whenever a location update occurs. Also, we use stepwise paging scheme using the mobile nodes' velocity in order to reduce the paging cost. We compare our scheme with the distance-based scheme through numerical analysis. Finally, we show that our proposed scheme is better than the distance-based scheme with an optimal distance threshold value for most mobility patterns.
Wireless Communications and Networking, 2003. WCNC 2003. 2003 IEEE; 04/2003
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ABSTRACT: This paper introduces a predictive paging scheme, called the
movement direction paging scheme (MDP), which is based on the movement
direction of a mobile host in order to reduce the paging cost in
personal communication services (PCS). In the movement direction paging
scheme, the visiting location registers (VLR) store the history of
movement directions for a mobile host in its database. The history of
movement direction for a mobile host is stored with compact records
revised by the mapping and reduction function of the mobile switching
center (MSC). The future movement direction of a mobile host can be
predicted by using these records stored at the database of the VLR. The
proposed scheme of movement direction paging is combined with a
movement-based registration scheme and related to the basic velocity
paging scheme (BVP). Analytical models of the basic velocity paging
scheme and the paging scheme for performance evaluation are provided and
the results demonstrate the cost-effectiveness of the proposed scheme
under various parameters
Vehicular Technology Conference, 1999. VTC 1999 - Fall. IEEE VTS 50th; 02/1999
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Proceedings of the 17th IASTED International Conference on Applied Informatics, February 15-18, 1999, Innsbruck, Austria; 01/1999
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Proceedings of the International Conference on Parallel and Distributed Processing Techniques and Applications, PDPTA 1999, June 28 - Junlly 1, 1999, Las Vegas, Nevada, USA; 01/1999
