• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.123.2-123.2
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• 2003

The cellular mechanisms by which excess exposure to the excitatory neurotransmitter glutamate can produce neuronal injury are unknown. In this study, we found that glutamate induced cell death at IC (50) of 100 microM on the cultured human SH-SY5Y neuroblastoma cells. It has been hypothesized that glutamate excitotoxicity is related with the elevation of calcium (Ca) levels. To determine the dependence of glutamate neurotoxicity on Ca environment, extracellular (EDTA) and intracellular (BAPTA/AM) chelator were used. (omitted)

• 한국미생물·생명공학회지
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• 제14권6호
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• pp.501-503
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• 1986

• 미생물학회지
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• 제30권6호
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• pp.558-563
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• 1992

녹색황세균인 Chlorobium limicola f.thiosulfaphilum NCIB 8327 의 성장은 암모늄, glutamine, glutamate 와 질소가스를 각각의 질소원으로 사용하여 배양한 것 중에서 질소가스를 제외하고는 거의 일정하였고, 황화수소만 있을 경우보다 티오황산을 첨가하였을 때 좀 더 잘자랐고, 아세트산을 더 첨가하였을 때 매우 잘 자랐다. 4가지 서로 다른 질소원으로 키운 세포들 중에서 glutamine synthetase 의 specific activity 는 glutamate 를 질소원으로 키운 세포의 파쇠액에서 최고 높았지만, glutamate synthase 의 경우는 거의 일정하였다. Glutamate 에서 키운 세포의 파쇠액 중에서 반응액의 암모늄의 농도가 높아진 경우, Glutamine synthetase 의 활성은 낮아지고, glutamate synthase 의 활성은 일정하며, glutamate dehydrogenase 의 활성은 높아졌다. 암모늄의 농도를 달리하여 키운 세포의 파쇄액들 중에서 반응액의 암모늄이온의 농도가 높아짐에 따라 높은 농도의 암모늄이온에서 키운 세포의 파쇄액에서의 glutamine synthetase 의 활성이 비교적 덜 불활성화 되엇다. Glutamine synthetase 는 methionine sulfoximine 의 농도라 높아짐에 다라 더 빨리 불활성화되었다. Glutamine synthetase 는 methionine sulfoximine 의 농도가 높아짐에 따라 더 빨리 불활성화되었다. Glutamine synthetase 는 빛에 있을 경우 활성이 증가하였고, 어두운 곳에서는 활성이 점차 낮아졌다. 온정한 세포에서의 수소발생은 빛에 의존하였고, 첨가된 암모늄 이온에 의해 저해되지만, netguibube sulfoximine 에 의해 곧바로 회복되었다. 수소발생이 빛에 의존하고, 암모늄이온에 의해 쉽게 저해되었다. Methionine sulfoximine 에 의해 빠르게 회복되는 것으로 보아, 본 균주는 nitrogenase 에 의해 수소밸생이 일어나며 glutamine synthetase 의 간접적인 조절을 받는 것으로 추정된다.

• Toxicological Research
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• 제18권4호
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• pp.355-362
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• 2002

Pathophysiological elevation of intracellular calcium concentration ($[Ca^{2+}]_1$) in the neuron has been considered as an important responsible factor in the neuronal cell damages. However the mechanism of increase of $[Ca^{2+}]_1$ and the relationship between $[Ca^{2+}]_1$ level and cytotocixity have not been fully demonstrated. In the present study, real-time alteration of $[Ca^{2+}]_1$and cellular response (cell damages) in the pheochromocytoma cells (PC12) stimulated by glutamate were investigated. Glutamate dose dependently decreased cell viability determined propidium iodide fluorescence method and morphology change. Conversely related with cell damages, glutamate dose dependently increased the level of［Ca$^{2+}$］$_{i}$ . To investigate the mechanism of glutamate-induced increase of $[Ca^{2+}]_1$,$[Ca^{2+}]_1$, was first measured in the cell cultured in calcium free media and in the presence of dantrolene, an inhibitor of calcium release from ryanodine receptor located in endoplasmic reticulum (ER). Similar to the increase$[Ca^{2+}]_1$ in the calcium-containing media, glutamate dose dependently increased $[Ca^{2+}]_1$ in the cell cultured in free calcium media. However pretreatment (2 hr) with 20~50 $\mu\textrm{M}$ dantrolene substantial lowered glutamate-induced increase of $[Ca^{2+}]_1$, suggesting that release of calcium from ER may be major sourse of increase of $[Ca^{2+}]_1$ in PC12 cells. Dantrolene-induced inhibition of $[Ca^{2+}]_1$ resulted in recovery of cytotoxicity by glutamate. Relevance of N-methy-D-aspartate (NMDA) receptor, a type of glutamte receptor on glutamate-induced incense of $[Ca^{2+}]_1$,$[Ca^{2+}]_1$ was also determined in the cells pretreated (2 hr) with NMDA receptor antagonist MK-80l. Glutamate-induced increase of $[Ca^{2+}]_1$ was reduced by MK-801 dose dependently. Furthermore, glutamate-induced cytotoxicity was also prevented by MK-80l. These results demonstrate that glutamte increase $[Ca^{2+}]_1$ dose dependently and thereby cause cytotoxicity. The increase of $[Ca^{2+}]_1$ may release from ER, especially through ryanodine receptor and/or through NMDA receptor Alteration of calcium homeostasis through disturbance of ER system and/or calcium influx through NMDA receptor could contribute glutamate-induced cell damages.s.

• Journal of Microbiology and Biotechnology
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• 제18권4호
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• pp.704-710
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• 2008

Glutamate availability in the argF-argR-proB${\Delta}$ strain of Corynebacterium glutamicum was increased by addition of glutamate to the cell or inactivation of the phosphoenolpyruvate carboxykinase activity and simultaneous overexpression of the pyruvate carboxylase activity to assess its effect on L-ornithine production. When glutamate was increased in an L-ornithine-producing strain, the production of L-ornithine was not changed. This unexpected result indicated that the intracellular concentration and supply of glutamate is not a rate-limiting step for the L-ornithine production in an L-ornithine-producing strain of C. glutamicum. In contrast, overexpression of the L-ornithine biosynthesis genes (argCJBD) resulted in approximately 30% increase of L-ornithine production, from 12.73 to 16.49 mg/g (dry cell weight). These results implied that downstream reactions converting glutamate to L-ornithine, but not the availability of glutamate, is the rate-limiting step for elevating L-ornithine production in the argF-argR-proB${\Delta}$ strain of C. glutamicum.

• 한국미생물·생명공학회지
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• 제17권6호
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• pp.552-555
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• 1989

Corynebacterium glutamicum의 NADPH-specific glutamate dehydrogenase를 이용하여 NADPH, NH$_4$Cl, $\alpha$-ketoglutarate의 기질에 대한 kinetics를 고찰하였다. 이들의 kinetic constants를 측정함으로서 정반응에로의 효소반응 기작은 첫번째 효소와 반응하는 기질이 NADPH 임을 확인할 수 있었다. Glutamate dehydrogenase 활성의 조절을 위한 metabolites의 효과를 고찰하여 본 결과 malate와 citrate 만이 효소에 억제 효과를 나타내었으며, potassium chloride는 효소활성에 가장 많은 영향을 주었다.

• Natural Product Sciences
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• 제18권1호
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• pp.26-31
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• 2012

Actinidia arguta (Actinidiaceae) has been reported to have several pharmacological effects such as anti-inflammatory, anti-allergic, and anti-oxidant activities. The present study investigated the protective activity of an ethanol extract from the leaf and stem of A. arguta against glutamate-induced neurotoxicity using cultured rat cortical neurons. Exposure of cultured cortical neurons to $500{\mu}M$ glutamate for 12 h triggered neuronal cell death. A. arguta inhibited glutamate-induced neuronal death and apoptosis, which were measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining, respectively. The increase of pro-apoptotic proteins, Bax and c-caspase-3, in glutamate-treated neurons was significantly inhibited by treatment with A. arguta. A. arguta also inhibited $500{\mu}M$ glutamate-induced elevation of intracellular calcium concentration ($[Ca^{2+}]_i$) and reactive oxygen species (ROS) generation, which were measured by fluorescent dyes, Fluo-4 AM and $H_2DCF$-DA, respectively. These results suggest that A. arguta may prevent glutamate-induced apoptotic neuronal death by inhibiting $[Ca^{2+}]_i$ elevation and ROS generation and, therefore, may have a therapeutic role for the prevention of neurodegeneration in cerebral ischemic diseases.

• 동의생리병리학회지
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• 제26권4호
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• pp.475-482
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• 2012

This study was designed to elucidate the mechanism of the cytoprotective effect of the Palmul-tang (PMT) on glutamate induced cytotoxicity in rat C6 glial cells. We determined the increase of cell viability by PMT on glutamate-induced death of C6 glial cell. On some experiments, glutamate induced cell death to be an apoptotic phenomena characterized by G1 arrest in cell cycle, chromatin condensation, DNA fragmentation in C6 glial cells. However, pre-treatment of PMT inhibited characteristic apoptotic phenomena. One of the main mediator of glutamate-induced cytotoxicity was known to generation of reactive oxigen species. In this study, PMT attenuated generation of reactive oxigen species by glutamate through down-regulation of NOX1 expression in C6 glial cells. Furthermore, PMT regulated Bcl2 families and caspase proteins, which contribute the cell survival or death. This study suggests that PMT may be candidate for both of therapeutic and protective prescription.

• The Korean Journal of Physiology
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• 제26권1호
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• pp.89-97
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• 1992

In hypoxic tissue conditions, pyruvate can not enter the Krebs cycle and lactic acid, produced from pyruvate, accumulates to induce lactic acidosis. Pyruvate, However, can also be converted to alanine by glutamate pyruvate transaminase, that could be enhanced by glutamate. Therefore, it would be a fundamental measure to treat the lactic acidosis in tissue hypoxic conditions when one can convert the accumulated lactic acid, through pyruvate, to alanine. To test the above hypothesis, we induced a lactic acidosis in cats and the effect of glutamate on recovery of acid base state and removal of the lactic acid from blood were assessed and the results were compared with those of bicarbonate administration, which is one of the most frequently used conventional measure for correction of the acid base state during lactic acidosis. The results were that glutamate and combined glutamate bicarbonate solutions not only restored the acid base status completely from the lactic acidosis in an hour or two, but also restored the blood level of lactate partially. We concluded that administration of glutamate solution to convert pyruvate into alanine is effective in preventing lactic acid accumulation and treating lactic acidosis.

• KSBB Journal
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• 제29권1호
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• pp.67-71
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• 2014

Planaria were recently reported to be a simple and sensitive model to investigate the mechanistic aspect of seizure and to screen potential anticonvulsants. Using planarian model, we analyzed the pharmacological effect of ukgansan (UGS), an oriental herbal medicine containing seven medicinal herbs, on the planarian locomotor velocity (pLMV) and glutamate-induced seizure-like activity (pSLA). To test whether D. japonica is suitable for studying anti-seizure agents, we investigated the effect of glutamate on pLMV and pSLA in D. japonica. In the present study we first confirmed that pSLA in D. japonica was induced by L-glutamate. Glutamate significantly produced pSLA in a dose dependent manner, but did not affect pLMV. These glutamate-induced paroxysms were decreased by antiepileptic drug, topiramate. A similar inhibitory effect on glutamate-induced pSLA was observed after the treatment of UGS. The present results suggest that UGS and its active constituents possess useful substance inhibiting seizure in planarian and that D. japonica provides a convenient model to search active herbs containing anti-seizure activity.