Neuroprotective mechanisms of dieckol against glutamate toxicity through reactive oxygen species scavenging and nuclear factor-like 2/heme oxygenase-1 pathway

Cui, Yanji,Amarsanaa, Khulan,Lee, Ji Hyung,Rhim, Jong-Kook,Kwon, Jung Mi,Kim, Seong-Ho,Park, Joo Min,Jung, Sung-Cherl,Eun, Su-Yong The Korean Society of Pharmacology 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.2

Glutamate toxicity-mediated mitochondrial dysfunction and neuronal cell death are involved in the pathogenesis of several neurodegenerative diseases as well as acute brain ischemia/stroke. In this study, we investigated the neuroprotective mechanism of dieckol (DEK), one of the phlorotannins isolated from the marine brown alga Ecklonia cava, against glutamate toxicity. Primary cortical neurons ($100{\mu}M$, 24 h) and HT22 neurons (5 mM, 12 h) were stimulated with glutamate to induce glutamate toxic condition. The results demonstrated that DEK treatment significantly increased cell viability in a dose-dependent manner ($1-50{\mu}M$) and recovered morphological deterioration in glutamate-stimulated neurons. In addition, DEK strongly attenuated intracellular reactive oxygen species (ROS) levels, mitochondrial overload of $Ca^{2+}$ and ROS, mitochondrial membrane potential (${\Delta}{\Psi}_m$) disruption, adenine triphosphate depletion. DEK showed free radical scavenging activity in the cell-free system. Furthermore, DEK enhanced protein expression of heme oxygenase-1 (HO-1), an important anti-oxidant enzyme, via the nuclear translocation of nuclear factor-like 2 (Nrf2). Taken together, we conclude that DEK exerts neuroprotective activities against glutamate toxicity through its direct free radical scavenging property and the Nrf-2/HO-1 pathway activation.

還元型 glutathione이 急性 에타놀 中毒 흰쥐의 肝 및 血液 數種代謝에 미치는 效果

曺晧哲,姜錫憲 慶北大學校 醫科大學 1981 慶北醫大誌 Vol.22 No.1

에타놀 急性 中毒때의 肝 및 血液의 代謝過程과 GSH의 投與가 에타놀 中毒에 미치는 效果의 一端을 알고자, 흰쥐를 材料로 하여 50%에타놀을 體重 100gm當 1.5㎖씩 經口的으로 單回投與하여 急性 에타놀 中毒을 일으켰고(EOH群), 그 前 3日間 每日 體重 100gm 當 5mg의 GSH溶液을 腹腔內로 注射한 後, 中毒을 일으킨 群(GSH+EOH 群)및 GSH만을 投與한 群(GSH群)에서 各各 24時間까지 經時的으로 Hct値, 에타놀 血中濃度, 肝蛋白量 및 GSH와 GSSG量, 그리고 血中 GSH 및 GSSG量을 測定하여 正常群과 比較하여 다음의 結果를 얻었다. 에타놀 血中濃度는 正常値인 145.0±12.0mg% (平均±標準誤差以下同)에 比하여 GSH群에서는 全實驗時間에 差異가 없었으나, EOH群 및 GSH+EOH에서는 1時間에서 各各 712.0±19.0mg% 및 668.0±16.Omg%로서 有意한 增加를 나타내었고 24時間까지 漸次 낮아지는 傾向을 보이나 正常値에 比해서는 모두 有意하게 높은 값을 나타내었다. 그리고 EOH群과 GSH+EOH群을 比較하면 各 實驗時間에서 서로 거의 差異를 나타내지 않았으나 GSH+EOH群이 若干 낮은듯한 傾向을 보였다. Hct値는 正常의 45.1±1.77%에 比하여 GSH群에서는 全實驗 時間에서 差異를 나타내지 않았으나 EOH群에서는 모두 正常値보다 높은 값을 나타내었고, 特히 6時間에서 最高値인 59.1±2.15%의 有意한 값을 나타낸 後 24時間까지 漸次 낮아져서 正常値에 가까와지는 傾向을 나타내었다. GSH+EOH群에서도 全體的인 傾向은 EOH群과 同一하였으나 EOH群보다는 若干 낮은 傾向을 나타내었다. 血中 GSH는 正常値인 6.85±0.4μ㏖/㎖에 比하여 GSH群은 實驗初期에는 높은 값을 나타내었다가 漸次 24時間까지는 正常値에 가까와지는 傾向 을 나타내는 反面, EOH群은 有意하게 낮은 값을 나타내었다가 24時間에서는 正常에 가까와지는 傾向을 나타내었고, GSH+EOH群에서는 EOH群보다는 높고 正常에 가까운 値를 나타 내었다. 血中 GSSG는 正常値 11.90±1.04μ㏖/㎖에 比하여 GSH群은 1~3時間에서는 높은 값을 나타내었다가 24時間에서는 正常値에 가까와졌고, EOH群 및 GSH+EOH群에서도 全實驗을 通하여 正常値보다는 높은 값을 나타내었으나, GSH+EOH群에 比해서는 EOH群이 全般的으로 낮은 값을 나타내는 傾向이었다. 肝蛋白量은 正常의 225.7±8.54mg/gm에 比해서 EOH群이나 GSH+EOH群에서는 모두 有意하게 높은 값을 나타내었고, EOH群이 GSH+EOH群보다 若干 낮은 傾向을 나타내었다. 肝 GSH는 正常의 9.20±0.72μ㏖/gm에 比하여 GSH群에서는 큰 差異가 없으나 EOH群에서는 有意하게 낮고, 特히 6時間에서 가장 낮은 값을 나타내었다. GSH+EOH群에서는 正常値보다는 大體로 낮은 값을 나타내었다. 肝 GSSG는 正常値인 5.21±0.48μ㏖/gm에 比하여 GSH群은 큰 差異가 없고, EOH群 및 GSH+EOH群에서는 正常보다 높은 傾向을 나타내었고 EOH群은 6 및 12時間에 가장 높은 값을, 그리고 GSH+EOH群은 1 및 3時間에 가장 높은 값을 나타내었다가 24時間에서는 正常値에 가까와졌다. 以上의 結果를 綜合할 때 GSH의 投與가 急性 에타놀 中毒에 있어 그 中毒狀能를 恢復함에 있어 相當히 有效하다고 恩料된다. Reduced glutathione (GSH) has been reported to be effective in some hepatic disorders and also in protecting the body against a certain toxic agents including ionizing radiation. However, little is known whether GSH is also effective in acute ethanol intoxication. In the present study, an effort was directed to clarify the possible effectiveness of GSH in the state of excessive ethanol ingestion to the point of acute intoxication. The protein, GSH and GSSG (oxidized glutathione) levels of the liver, and the GSH and GSSG levels of the blood as well as hematocrit (Hct) and blood ehtanol concentration were chosen as the parameters of the hepatic or blood metabolism. The healthy and fully matured albino rats of either sex were used, and 1.5㎖ of 50% ethanol per 100gm of body weigilt was given by oral intubation to produce the acute ethanol intoxication (EOH group). GSH in the dose of 5mg per 100gm body weight for three days was intraperitoneally injected either alone (GSH group) or prior to the ethanol intoxication (GSH+EOH group) which was initiated immediately after the last injection of GSH. The rat was sacrificed at 1, 3, 6, 12 and 24 hours in all the group by cutting the carotid arteries and the blood sample was obtained. The liver was immediately excised and placed into an ice-cold saline until ready for use. The protein of the liver was measured by the method of Lowry, et at, GSH level of the liver and blood by Ellman's method and GSSG by the electrolytic reduction method described by Dohan and Woodward. Hematocrit was determined by the conventional microhematocrit method using Adams microhematocrit centrifuge and reader, and the blood ethanol concentration was measured by the method of William, et al. The results obtained were compared with the normal and summarized as follows. The blood ethanol concentration in both EOH and GSH+EOH groups reached the highest level of 712.0±10.9mg% and 668.0±16.Omg%, respectively, at one hr and gradually declined until 24 hrs after the ethanol ingestion, but all the experimental hour showed a significant increase from the normal value of 145.0±12.Omg%. Between GSH+EOH group and EOH group, the former showed a slightly lowered value than the latter, though the difference was not significant. The highest Hct values were obtained at 6th hr and significantly elevated values continued throughtout the experiment in both EOH and GSH+EOH group, but GSH+EOH group showed a lower level of Hct comparing with EOH group. The blood GSH level in GSH group showed elevated value in the first part of the experiment followed by a gradual decline to the normal value of 6.85±0.40μmo1/㎖ at 24 hrs. EOH group, however, showed significantly lower value throughout the experiment with a recovery to the normal virtue at 24th hr. In GSH+EOH group, all the value was higher than in EOH group. The blood GSSG level in GSH group showed higher values at 1-3 hrs with a tendency of recovering to the normal value of 11.90±1.04μmo1/㎖ at 24th hr. Both EOH and GSH+EOH groups showed elevated values throughout the experiment, but GSH+EOH group showed a tendency of higher value than EOH group. The liver protein levels in both EOH and GSH+EOH groups showed significantly elevated values throughout the experiment with a tendency of higher value in GSH+EOH group comparing with EOH group. The liver GSH level in EOH group was significantly decreased comparing with the normal value of 9.2±0.72μmo1/㎖ with the lowest value at 6th hr. In GSH+EOH group, the liver GSH level was generally higher than in EOH group. The liver GSSG level in EOH group showed the highest value at 6 and 12 hrs while GSH+EOH group showed the highest value at 1 and 3 hrs with a tendency of recovering to the normal value of 5.21±0.48μmol/㎖ at 24 hrs. From the above, it may be concluded that the administration of GSH is effective to a certain degree in acute ethanol intoxication.

Separate gauge orbit quantivation of massive Yang-Mills gauge theory

박철수,유광호 대불대학교 1996 論文集 Vol.2 No.2

양-밀스 커넥션의 게이지 변환에 대한 자유도를 커넥션 공간의 프린시팔번들 구조에 따라 매개변수화 하였다. 이 매개변수를 사용하여 질량을 가진 양-밀스 게이지 이론의 일반적인 모형에 대한 양자화 가능성을 밝혔다.

低開發國 一次産品市況의 變遷에 관한 고찰

金浩哲 東國大學校 1974 論文集 Vol.13 No.-

The first product markets in the underdeveloped countries can be affected by their own conditions, but the most important element to be considered is the industrial fluctuation in the developed countries; a recession neglizible for the developed countries can deal a serious blow on the under developed countries. furthermore, the restriction of import on the product tightened in 1950's and 1960's caused the recessions in the underdeveloped countries. 1. The Market condition of the first product in 1950's and 1960's a. the long-term trend the causes for the worsening condition of the first product market in 1950's and 1960's are; a) import coefficient; America, which is low in import coefficient, became the center of world economy in 20th century and failed to make a development in harymony with the countries who supply the first product. b) the development of the substitutes; such as synthetic rubber and fibers played an important role in worsening the market condition of the first product. c) an error in the strategy of development; the worsening of the international market condition of the first product could be prevented by the use of the product for the domestic economic development. but the underdeveloped countries did not developed the economic field related with the first product. d) the increase in the worldwide supply ability; after the World War Ⅱ the supply ability of the first product increased not only in the underdeveloped countries but also in the developed countries such as America. b. the short-term trend caused by the fluctuation in the developed countreis. It is only natural for the underdeveloped countries supplying the first product to be affected by the fluctuation in the developed countreis but the question is the price of the first product is relatively low compared with the industrial product in the developed countries even in a boom period. a) the recession in 1957-58; during this period decrease in the industrial output in America is only 2%, and the price of the industrial product in ther-developed countries fell about 1%, while that of the first product in the underdeveloped countries did 6%. b) the recession in 1967; in March through August 1967, the prices of the first product feel sharply; copper 47%, rubber 29%, sugar 27%. 2. The Market condition of the first product in 1970's. a. the recession in 1970-71 (which caused the so-called stagflation) the index of the export prices in the developed countries in the first quarter of 1974 shows 3.6% rise compared with the previous year, while that of the import prices 2.7% rise. b. the excessive boom With President Nixon's New Economic policy of August 15, 1971, economy of America began the rising along with the other countries, America experienced the boom of more than 20 months, recording 15.2% of the rate of the nominal growth and 8% of the rate of the real growth in the first quarter of 1973. with the improvement of the market condition of the first product at home and the underdeveloped countries. c. the worldwide resource problem and the second stagflation With the worldwide economic development, the demand for the first product increased sharply, but as the resources, especially the important ones such as iron and energy, are limited in quantity, the resource shortage became one of the most difficult problem the world faces now, and the world economy experienced another stagflation in 1973 as the Arab used oil as weaponry and many countries tried to check the excessive boom. Prices of agricultural products all over the world are rising because of the bad harvest owing to the abnormal and unseasonable weather in many years. However the rise of the prices first product is helpful to the underdeveloped countries, in spite of the worldwide stagflation.

韓國人의 飮酒樣態에 關한 硏究

曺晧哲,金政煇,李時炯 大韓神經精神醫學會 1975 신경정신의학 Vol.14 No.1

Alcohol has long been used by humankind for the various reasons, eg, emotional, ceremonial, and even as a tranquilizer etc. Thus drinking pattern of a certain group is well reflected on its cultural climate. It is very this reason that, in the field of social science, one avenue to understand the pattern of culture is via analyzing that of drinking. Unfortunately, however, not many studies have been done about so called "social drinker" camparing to the numerous studies done about "alcoholism". The authors attempted to study a general pattern of drinking among Korean male adult. Two thousands copies of questionnaire which consists of 35 items, were distributed to the college students and parents of school children randomly as follows: 1) To compare the geographical differences; city of Taegu and town of Sang-Joo were selected for study. 2) To compare the generational defferences; Fresh-man and sophomore classes at Kyungpook National University were selected. Some of the meaningful findings are as follows; 1) Two thirds of Korean male adult drink alcohol occasionally, to be defined as so called "social drinker", and a third might be called "regular drinker". 2) Majority drink alcohol for the purpose of more smooth interpersonal relation, rather than escape from reality. 3) Traditionally as it has been, still majority of Korean male are quite against female drinking. 4) Majority drink low concentrated alcohol in larger amount. 5) Majority drink outside of home which is quite different from our tradition, thus its considered modernization slowly has begun to effect drinking pattern also. 6) Student group drinks for the emotional reason and they are more permissive toward the female drinking.

Non-Kirchhoff Modeling of Radiation for Global Warming

박철수,유광호 대불대학교 2001 論文集 Vol.7 No.1

지구온난화에 대한 온실효과의 영향을 고려하기 위하여 키르히호프 법칙을 따르지 않는 단순 복사 모형을 만든다. 이 복사 모형에 따른 결과로써, 지구온난화의 주요 양상들을 적절하게 설명할 수 있다.

母子간에 생긴 Folie a Deux 一例의 力動的 考察

조호철 大韓神經精神醫學會 1975 신경정신의학 Vol.14 No.4

The author analized some dynamic processes of forming "Folie a Deux" in a case of schizophrenic mother and son. Contrary to the previous report in which cases are usually found in a socially isolated living environment, the presenting case came from a socially active large family in a big city. Again despite of the advise to separate the pair for treatment, this case was hospitalized at the same time ward and yet the favorable result had been obtained. The summary of this case study is presented along with discussion in the following sequence; Family background of mother, Marital dynamic of family in discussion along with process of transmission of delusion from mother to son and some comments on therapeutic approach. 1) Several members had been found to be psychotic, mostly affective in nature, in the maternal family tree and the early family environment was also such that affectively cold, distant and paranoidal potential in the mother would be easily understood. 2) Marital dynamic of this family was considered to be a typical one of schism in which the presenting pair was totally isolated from the rest of family, and this had become a contributing factor in forming a folie a deux along with son's weak ego boundary. 3) With an active therapeutic intervention, it was thought to be rather beneficial to treat two patients on the same ward.

메주종류를 달리하여 제조한 된장 숙성중의 향미특성 변화

이강권,이철호 한국산업식품공학회 2003 산업 식품공학 Vol.7 No.1

전통식 된장 및 Aspergillus oryzae koji와 Bacillus subtilis의 세균 koki를 이용한 된장을 제조하여 30℃에서 90일간 숙성하며, 숙성기간동안의 향미특성 차이를 측정하였다. 총 유리아미노산 량은 471.71~1708.47mg%로 숙성이 진행됨에 따라 증가하는 경향을 나타내었다. 일본식 된장은 arginine, proline, leucine 함량이 비교적 높아 타 된장과 다른 경향을 나타내었으나, 3종류 된장 시료 모두 glutamic acid, leucine이 공통적으로 많은 비율이 존재하였다. 유기산은 전통식 된장은 oxalic acid 와 citric acid가 검출되었고, 일본식 된장은 담금 직후부터 숙성 90일까지 oxalic acid, citric acid, malic acid가 검출되었는데, malic acid는 담금 직후 23.52mg%를 나타낸 후, 숙성 90일에는 202.18mg%로 약 10배정도 급격히 증가하였다. 혼합식 된장은 oxalic acid, mal 금초기 371.65~623.48 mg%에서 숙성 90일 이후 246.09~343.4 mg%로 감소하였으며, 모든 시료에서 glucose 와 galactose의 함량이 가장 높았다. 지방산 분석 결과 myristic, palmitic, stearic, oleic, linoleic, linolenic acid가 확인 되었다. 측정된 지방산 중 linoleic acid가 38.56~51.86%로서 가장 많은 비율을 나타내었고, oleic acid는 19.09~27.51%, palmitic acid는 7.37~10.89%, linolenic acid는 5.50~7.52~, myristic acid는 1% 미만이었다. 향기성분 분석 결과 alcohol류 10종, ester 류 19종, acid류 5종, aldehydes 류 9종, ketones류 5종, sulfur화합물 1종, hydrocarbon 류 16종, 기타 13종 등 총 78개의 화합물이 검출되었다. 전통식 된장에서 검출된 성분은 모두 60종이었으며, 일본식 된장은 61종, 혼합식 된장은 72종이었다. 3종류의 된장에서, 숙성 전기간 동안 검출된 성분은 ethanol, 2,3-butanedione, pentyl-acetate, 3-methyl-butanal, 2-methyl-1-butanol, 2-pentylfuran, 1-limonene, 2-metoxyphenol 등 8종이었다. Three types of Doenjang, using Korean menu (KM), Japanease koji(JK) and modified meju mix of A. oryzae meju and B. subtilis meju(MAB) were manufactured and salt aged for 90 days at 30℃. The major free amino acids of Doenjang were glutamic acid and leucine. Among the free amino acids in Doenjang, isoleucine was the most abundant component at the begiginning of aging period. Among the organic acids in JK Doenjang, malic acid increased remarkably during salt aging. It contained higher amounts of free sugars than the others. The total amount of free sugars in Doenjang decreased during salt aging. In fatty acid compositions of Doenjang, myristic, palmitic, stearic, oleic, linoleic, linolenic acid were analyzed, and the most abundant fatty acid was linoleic acid, 38.56∼51.86%. The volatile flavor compounds of Doenjang were analyzed and seventy eight compounds were identified. Ethanol was found to be one of the most abundant volatile flavor compound. In JK Doenjang, ethanol increased 400 times during fermentation. The number of volatile compounds detected immediately after salt aging of JK Doenjang were 28 and increased to 50 compounds after 60 days of salt aging. In MAB Doenjang, most of the volatile compounds were found after 30 days of salt aging. Eight volatile compounds such as ethanol, 2,3-butanedione, pentyl-acetate, 3-methyl-butanal, 2-methyl-1butanol, 2-pentylfuran, 1-limonene, 2-metoxyphenol were found in all samples with relatively abundant amount.

메주종류를 달리하여 제조한 된장 숙성중의 관능적 품질특성 변화

이강권,이현덕,이철호 한국산업식품공학회 2003 산업 식품공학 Vol.7 No.1

전통식 된장 및 Aspergillus oryzae koji와 Bacillus subtilis의 세균 koji를 이용한 된장을 제조하여 30℃에서 90일간 숙성하며, 숙성기간동안의 관능적 품질특성 차이를 측정하였다. 전통식 된장은 특히, 쓴맛이 타 된장에 비해 높은 값을 나타냈으며, 일본식 된장으 맛의 어우러짐 및 전반적인 맛의 품질에 있어, 타 된장에 비해 평가치가 높았다. 주성분 분석에 의하여 3종류의 된장의 특성을 구분할 수 있었는데, 전통식 된장은 관능적인 향기에서는 메주냄새의 특성이 강하게 발현되는 된장으로 구분 될 수 있었다. 일본식 된장은 관능적인 맛은 구수한맛, 단맛, 맛의 어우러짐, 전반적인 맛품질, 관능적인 향기에서는 전반적인 향품질의 특성이 강하게 발현되는 된장으로 나타났다. 그리고, 혼합식 된장은 관능적인 맛에서는 단맛, 구수한맛, 짠맛, 신맛, 외관에서는 갈색, 밝기, 관능적 향기에서는 구수한 냄새, 술냄새, 산패취, 짠냄새, 단냄새의 특성이 강하게 나타나는 된장의로 구분되어 질 수 있었다. 이 중 관능적인 맛의 특성은 일본식 된장과 혼합식 된장이 상관관계가 높게 나타났다. 따라서, 각기 다른 메주로 제조한 된장은 숙성에 따라 독특한 특성의 된장으로 진행되어 감을 알 수 있었다. Three types of Doenjang, using Korean menu (KM), Japanease koji (JK) and modified meju mix of A. oryzae meju and B. subtilis meju (MAB) were manufactured and salt aged for 90 days at 30℃. The changes of sensory characters of flavor components in Doenjang during 90 days were examined. All results were analyzed with statistics such as ANOVA and principal component analysis (PCA). In the PCA result of the three types of Doenjang, first two principal components could be explained by 90.73% of all taste and harmonized taste. MAB Doenjang was chiefly chiefly correlated with sweet taste, nutty taste, salty taste and sour taste and in odor compounds, first two principal components could be explained 86.58% of all components. JK Doenjang was highly correlated with odor acceptability and MAB Doenjang was correlated with sweet odor, nutty odor, alcoholic odor, racid odor and off odor. KM Doenjang was close related with meju odor.

The Effect of Korean Soysauce and Soypaste Making on Soybean Proteion Quality

Cherl-Ho Lee(이철호) 한국식품과학회 1976 한국식품과학회지 Vol.8 No.2