• Title/Summary/Keyword: Glutamate-induced toxicity

Search Result 42, Processing Time 0.026 seconds

Effects of Curcumin, the Active Ingredient of Turmeric(Curcuma longa), on Regulation of Glutamate-induced Toxicity and Activation of the Mitogen-activated Protein Kinase Phosphatase-1 (MKP-1) in HT22 Neuronal Cell

  • Lee, Sang-Hyun;Yun, Young-Gab
    • Natural Product Sciences
    • /
    • v.15 no.1
    • /
    • pp.32-36
    • /
    • 2009
  • Glutamate causes neurotoxicity through formation of reactive oxygen species and activation of mitogen-activated protein kinase (MAPK) pathways. MAPK phosphatase-1 (MKP-1) is one of the phosphatases responsible for dephosphorylation/deactivation of three MAPK families: the extracellular signal-regulated kinase-1/2 (ERK-1/2), the c-Jun N-terminal kinase-1/2 (JNK-1/2), and the p38 MAPK. In this report, the potential involvement of MKP-1 in neuroprotective effects of curcumin, the active ingredient of turmeric (Curcuma longa), was examined using HT22 cells. Glutamate caused cell death and activation of ERK-1/2 but not p38 MAPK or JNK-1/2. Blockage of ERK-1/2 by its inhibitor protected HT22 cells against glutamate-induced toxicity. Curcumin attenuated glutamate-induced cell death and ERK-1/2 activation. Interestingly, curcumin induced MKP-1 activation. In HT22 cells transiently transfected with small interfering RNA against MKP-1, curcumin failed to inhibit glutamate-induced ERK-1/2 activation and to protect HT22 cells from glutamate-induced toxicity. These results suggest that curcumin can attenuate glutamate-induced neurotoxicity by activating MKP-1 which acts as the negative regulator of ERK-1/2. This novel pathway may contribute to and explain at least one of the neuroprotective actions of curcumin.

Effect of Sopung-tang on Glutamate-Induced Apoptosis in C6 Glial Cells (소풍탕(疎風湯)이 Glutamate에 의한 C6 Glial Cell의 Apoptosis에 미치는 영향)

  • Jeong, Seung-Won;Choi, Chul-Won;Kim, Bong-Sang;Moon, Byung-Soon
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.22 no.6
    • /
    • pp.1423-1430
    • /
    • 2008
  • The water extract of Sopung-tang(SPT) has been traditionally used for treatment of psycologic disease and brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of SPT rescues cells from these disease. Therefore, this study was designed to investigate the effect of SPT on the glutamate-induced toxicity of rat C6 glial cells. SPT have protective effects in glutamate-induced toxicity, which was revealed as apoptosis characterized by chromatic condensation and fragmentation and the loss of mitochondrial membrane potential in C6 glial cells. Also, SPT have inhibited the active form of caspase-3 and PARP and significantly protected the apoptotic phenomena by glutamate toxicity in C6 glial cells. However, SPT significantly recovered the depletion of GSH and inhibited the generation of ROS by glutamate in C6 glial cells. In addition, both SPT and antioxidants such as GSH and NAC protected the glutamate-induced cytotoxicity in C6 glial cells, indicating that SPT possibly have antioxidative effect. Specially, SPT were showed transcriptional factor significantly increased the activation of NF-${\kappa}B$ using the analysis of NF-${\kappa}B$ luciferase reporter system in C6 glial cells. These NF-${\kappa}B$ activation protected cells from glutamate-induced toxicity to generate the heme oxygenase-1(HO-1). Taken together, we suggest that SPT have protective effects in glutamate-induced toxicity via a antioxidative mechanism.

Ethanol Extract from Asparagus Cochinchinensis Attenuates Glutamate-Induced Oxidative Toxicity in HT22 Hippocampal Cells (HT22 해마세포의 oxidative toxicity에 대한 천문동 유래 에탄올추출물의 보호 효과)

  • Pak, Malk Eun;Choi, Byung Tae
    • Journal of Life Science
    • /
    • v.26 no.12
    • /
    • pp.1458-1465
    • /
    • 2016
  • We investigated the neuroprotective effect of an ethanol extract from Asparagus cochinchinensis (AC) against glutamate-induced toxicity in the HT22 hippocampal cell, which is an ideal in vitro model for oxidative stress. The neuroprotective effects of AC in HT22 cells were evaluated by analyzing cell viability, lactate dehydrogenase (LDH), flow cytometry for cell death types, reactive oxygen species (ROS), mitochondria membrane potential (MMP), and Western blot assays. In the cell death analysis, AC treatment resulted in significantly attenuated glutamate-induced loss of cell viability with a decrease in LDH release. AC treatment also reduced glutamate-induced apoptotic cell death. In the ROS and MMP analysis, AC treatment inhibited the elevation of intracellular ROS induced by glutamate exposure and the disruption of MMP. In oxidative stress-related proteins analysis, AC treatment inhibited the expression of poly ADP ribose polymerase and heme oxygenase-1 by glutamate. These results indicate that AC exerts a significant neuroprotective effect against glutamate-induced hippocampal damage by decreasing ROS production and stabilizing MMP. Thus, AC potentially provides a new strategy for the treatment of oxidative stress-related diseases.

Effects of Gwibitang on Glutamate-induced Death in Rat Neonatal Astrocytes (귀비탕이 Glutamate에 의한 성상세포의 손상에 미치는 영향)

  • 전희준;박세욱;이인;문병순
    • The Journal of Korean Medicine
    • /
    • v.25 no.2
    • /
    • pp.184-193
    • /
    • 2004
  • Objectives: This study was designed to investigate effects of Gwibitang on the glutamate-induced toxicity of primary rat neonatal astrocytes. Methods and Results: Gwibitang significantly recovered the glutamate-induced apoptosis and inhibited the generation of $H_2O_2$ in astrocytes. In addition, both Gwibitang and antioxidants such as GSH reduced the glutamate-induced cytotoxicity in astrocytes, indicating that Gwibitang possibly had an antioxidative effect. Moreover, Gwibitang also inhibited the glutamate-induced degradation of Bcl-2 protein and poly(ADP)-ribose polymerase (PARP) in astrocytes. Conclusions: We suggest that Gwibitang has protective effects on glutamate-induced cytotoxicity via an antioxidative mechanism.

  • PDF

Experimental Study on the Effect of L-Glutamate to Acute Myocardial Toxicity by Doxorubicin (Doxorubicin 에 의한 급성 심근독성과 L-Glutamate 의 효과에 관한 실험적 연구)

  • Park, Seong-Dal;Kim, Song-Myeong;Jeong, Hwang-Gyu
    • Journal of Chest Surgery
    • /
    • v.22 no.3
    • /
    • pp.436-447
    • /
    • 1989
  • The effect of Glutamate to myocardial toxicity induced by doxorubicin was studied with 20 male rats. 20 rats divided into 4 subgroups, 1st group was taken for normal control group without any treatment, 2nd group was injected with only doxorubicin, 3rd group was injected with L-glutamate and doxorubicin, and 4thd group was injected with only L-glutamate [all injections were done intraperitoneally]. Observations were made to each group on their gross findings, body weight, and electrocardiography, complete blood count and serum level of creatine phosphokinase. The results were as follows; l. In 1st group, we found no changes. 2. In 2nd group, there were many changes which were loss of body weight, dehydration, loss of body hair, diarrhea and death, in addition, elevation of CPK-MB isoenzyme and changes in EKG due to myocardial damage, leukopenia, thrombocytopenia were also found. 3. In 3rd group, there were more toxic effects containing 2 death cases, compared to 2nd group. 4. In 4th group, we found no specific changes except weight gain. These results suggest that L-glutamate which is intermediate of Krebs cycle may worsen the doxorubicin-induced myocardial toxicity.

  • PDF

Quercetin ameliorates glutamate toxicity-induced neuronal cell death by controlling calcium-binding protein parvalbumin

  • Kang, Ju-Bin;Park, Dong-Ju;Shah, Murad-Ali;Koh, Phil-Ok
    • Journal of Veterinary Science
    • /
    • v.23 no.2
    • /
    • pp.26.1-26.12
    • /
    • 2022
  • Background: Glutamate is the main excitatory neurotransmitter. Excessive glutamate causes excitatory toxicity and increases intracellular calcium, leading to neuronal death. Parvalbumin is a calcium-binding protein that regulates calcium homeostasis. Quercetin is a polyphenol found in plant and has neuroprotective effects against neurodegenerative diseases. Objectives: We investigated whether quercetin regulates apoptosis by modulating parvalbumin expression in glutamate induced neuronal damage. Methods: Glutamate was treated in hippocampal-derived cell line, and quercetin or vehicle was treated 1 h before glutamate exposure. Cells were collected for experimental procedure 24 h after glutamate treatment and intracellular calcium concentration and parvalbumin expression were examined. Parvalbumin small interfering RNA (siRNA) transfection was performed to detect the relation between parvalbumin and apoptosis. Results: Glutamate reduced cell viability and increased intracellular calcium concentration, while quercetin preserved calcium concentration and neuronal damage. Moreover, glutamate reduced parvalbumin expression and quercetin alleviated this reduction. Glutamate increased caspase-3 expression, and quercetin attenuated this increase in both parvalbumin siRNA transfected and non-transfected cells. The alleviative effect of quercetin was statistically significant in non-transfected cells. Moreover, glutamate decreased bcl-2 and increased bax expressions, while quercetin alleviated these changes. The alleviative effect of quercetin in bcl-2 family protein expression was more remarkable in non-transfected cells. Conclusions: These results demonstrate that parvalbumin contributes to the maintainace of intracellular calcium concentration and the prevention of apoptosis, and quercetin modulates parvalbumin expression in glutamate-exposed cells. Thus, these findings suggest that quercetin performs neuroprotective function against glutamate toxicity by regulating parvalbumin expression.

Effects of Gwibitang on Glutamate-induced Apoptosis in C6 Glial Cells (귀비탕이 Glutamate에 의한 C6 Glial Cell의 Apoptosis에 미치는 영향)

  • 강익현;이인;한상혁;문병순
    • The Journal of Korean Medicine
    • /
    • v.22 no.4
    • /
    • pp.45-57
    • /
    • 2001
  • Objectives : The water extract of Gwibitang (GBT) has been traditionally used for treatment of psychologic disease and brain damage in Oriental Medicine, This study was designed to investigate the effect of GBT on the glutamate-induced toxicity of rat C6 glial cells. Methods : The cultured cells were pretreated with GBT and exposed to glutamate, The cell damage was assessed by using MTT assay and Hoechst, IC-l staining, Results : GBT had protective effects in glutamate-induced cytotoxicity, which was revealed as apoptosis characterized by chromatic condensation and the loss of mitochondrial membrane potential in C6 glial cells. However, GBT and glutamate had no effect in the activation of caspase family cysteine proteases including caspase-3, -8 and -9 proteasesin C6 glial ce]]s, GBT significantly recovered the depletion of GSH and inhibited the generation of $H_2O_2$ by glutamate in C6 glial cells. In addition, both GBT and antioxidants such as GSH and NAC protected the glutamate-induced cytotoxicity in C6 glial cells, indicating that GBT possibly has antioxidative effect. Moreover, GBT also inhibited the glutamate-induced degradation of $IkB{\alpha}$ in C6 glial cells, This result suggest that GBT has some inhibitory effects on the transcriptional activation of $NF-_{k}B$. Conclusions : GBT has protective effects in glutamate-induced cytotoxicity via an antioxidative mechanism.

  • PDF

Inhibitory Effects of Xiaoshuan Zaizao Wan on Excitotoxic and Oxidative Neuronal Damage Induced in Primary Cultured Rat Cortical Cells (일차 배양한 흰쥐 대뇌피질세포의 흥분성 및 산화적 신경세포손상에 대한 소전재조환의 억제효과)

  • 조정숙
    • YAKHAK HOEJI
    • /
    • v.47 no.6
    • /
    • pp.369-375
    • /
    • 2003
  • Xiaoshuan Zaizao Wan (XZW) has been used in China to improve hemiplegia, deviation of eye and mouth, and dysphasia due to cerebral thrombosis. To characterize pharmacological actions of XZW, we evaluated its effects on neuronal cell damage induced in primary cultured rat cortical cells by various oxidative insults, glutamate or N-methyl-D-aspartate (NMDA), and $\beta$-amyloid fragment ($A_{\beta(25-35)}$). XZW was found to inhibit the oxidative neuronal damage induced by $H_2O_2$, xanthine/xanthine oxidase, or $Fe^{2+}$/ascorbic acid. It also attenuated the excitotoxic damage induced by glutamate or NMDA. The NMDA-induced neurotoxicity was more effectively inhibited than the glutamate-induced toxicity. In addition, we found that XZW protected neurons against the $A_{\beta(25-35)}$-induced toxicity. Moreover; XZW exhibited dramatic inhibition of lipid peroxidation in rat brain homogenates and mild 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity. Taken together; these results demonstrate that XZW exerts neuroprotective effects against oxidative, excitotoxic, or $A_{\beta(25-35)}$-induced neuronal damage. These findings may provide pharmacological basis for its clinical usage treating the sequelae caused by cerebral thrombosis. Furthermore, XZW may exert beneficial effects on Alzheimer's disease and other oxidative stress-related neurodegenerative disorders.

Cytoprotective Constituents of Alpinia katsumadai Seeds Against Glutamate-Induced Oxidative Injury in HT22 Cells

  • Jeong, Gil-Saeng;Li, Bin;Lee, Dong-Sung;Byun, Erisa;Kang, Dae-Gill;Lee, Ho-Sub;Kim, Youn-Chul
    • Natural Product Sciences
    • /
    • v.13 no.3
    • /
    • pp.268-271
    • /
    • 2007
  • Glutamate-induced oxidative injury contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as epilepsy and ischemia. Bioassay-guided fractionation of the MeOH extract of the seeds of Alpinia katsumadai Hayata (Zingiberaceae) furnished three phenolic compounds, alpinetin (1), pinocembrin (2), and (+)-catechin (3). Compounds 2 and 3 showed the potent neuroprotective effects on glutamate-induced neurotoxicity and reactive oxygen species (ROS) generation in the mouse hippocampal HT22 cells. In addition, Compounds 2 and 3 showed significant DPPH free radical scavenging effect. These results suggest that compounds 2 and 3 could be the effective candidates for the treatment of ROS-related neurological diseases.

Rhus verniciflua Stokes Attenuates Glutamate-induced Neurotoxicity in Primary Cultures of Rat Cortical Cells

  • Jeong, Eun-Ju;Sung, Sang-Hyun;Kim, Jin-Woong;Kim, Seung-Hyun;Kim, Young-Choong
    • Natural Product Sciences
    • /
    • v.14 no.3
    • /
    • pp.156-160
    • /
    • 2008
  • The methanolic extract of Rhus verniciflua Stokes (RVS-T) and its fractions (RVS-H, RVS-C, RVS-E and RVS-B) showed significant neuroprotective activity against glutamate-induced toxicity in primary cultures of rat cortical cells. RVS-B, which showed the most potent neuroprotective activity, was further fractionated to yield RVS-B5. Treatment of cortical cells with the RVS-T, RVS-B and RVS-B5 reduced the cellular ROS level and restored the reduced activities of glutathione reductase and SOD induced by glutamate. Although, the activity of glutathione peroxidase was not virtually changed by glutamate, RVS-B5 increased the glutathione peroxidase activity. In addition, these three tested fractions significantly restored the content of GSH which was decreased by glutamate insult in our cultures. Taken together, it could be postulated that RVS extract, in particular its fraction RVS-B5, protected neuronal cells against glutamate-induced neurotoxicity through acting on the antioxidative defense system.