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Functional Studies of Tyrosine 108 Residue in the Active Site of Human Glutathione S-Transferase P1-1

  • Park, Hee-Joong;Koh, Jong-Uk;Ahn, So-Youn;Kong, Kwang-Hoon
    • Bulletin of the Korean Chemical Society
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    • v.26 no.3
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    • pp.433-439
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    • 2005
  • To gain further insight on the relationship between structure and functions of glutathione S-transferase (GST), the three tyrosine 108 mutants, Y108A, Y108F, and Y108W, of human GST P1-1 were expressed in Escherichia coli and purified to electrophoretic homogeneity by affinity chromatography on immobilized GSH. The substitution of Tyr 108 with alanine resulted in significant decrease of the GSH-conjugation activity and the GSH peroxidase activity, but approximately 63% increase of steroid isomerase activity toward ${\Delta}^5$–[androstene 3,17-dione. On the other hand, the substitution of Tyr 108 with phenylalanine resulted in decreases of $k_{cat}\;and\;k_{cat}/K_m{^{EPNP}}$ by 2 orders of magnitude, suggesting that Tyr 108 residue of hGSTP1-1 are considered to be important for the catalysis and the binding of the epoxide substrates. The substitution of Tyr 108 with tryptophan resulted in significant decreases of the specific activities toward EPNP, cumene hydroperoxide and ${\Delta}^5$–ndrostene 3,17-dione, but approximately 2-fold increase on the enzyme-catalyzed addition of GSH to DCNB. We conclude from these results that Tyr 108 in hGST P1-1 plays very different roles depending upon the nature of the electrophilic substrates.

Antioxidative Action of Corni Fructus Aqueous Extract on Kidneys of Diabetic Mice

  • Kim, Hye-Jeong;Kim, Bae-Hwan;Kim, Young-Chul
    • Toxicological Research
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    • v.27 no.1
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    • pp.37-41
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    • 2011
  • This study investigated the antioxidative action of Corni Fructus aqueous extract on kidneys of diabetic mice. The electron donating abilities of Corni Fructus aqueous extract and its antioxidant activities (XO, SOD, CAT, GST, eNOS) in kidneys of C57BL/6 or db/db mice were evaluated. For in vivo study, seven week-old male mice were divided into normal control group (NC, C57BL/6 mice), diabetic control group (DC, db/db mice) and Corni Fructus (500 mg/kg/day for 8 weeks) treated diabetic group (DCF, db/db mice). The electron donating abilities of Corni Fructus aqueous extract exhibited 7%, 24.4%, and 42.7% at concentrations of 100, 500, and $1000\;{\mu}g/ml$, respectively. The activity of XO in the DCF group was significantly lower than the DC group by 35% (p < 0.05). The SOD activity was significantly higher in the DCF group than the DC group by 26% (p < 0.05). The activities of CAT and GST were lowered in the DCF group than the DC group by 26% (p < 0.05) and 7.6%, respectively. The mRNA expression of eNOS in kidneys was lower in the DCF group than the DC group by 24%. These results indicate that Corni Fructus reduced oxidation stress as evidenced by the restoration of the enzymatic antioxidative defense system in renal tissues of db/db mice. It is suggested that these antioxidative actions of Corni Fructus on renal tissues in db/db mice could contribute to its renoprotective effects on diabetic nephropathy.

The Effects of Reduced L-glutathione on Renal Ischemia-Reperfusion Injury in Pigs (돼지에서 신장 허혈 관류 손상에 미치는 환원형 L-glutathione의 효과)

  • Lee, Jae-Yeon;Kim, Hyun-Soo;Jee, Hyun-Chul;Jeong, Seong-Mok;Cho, Sung-Whan;Park, Chang-Sik;Kim, Myung-Cheol
    • Journal of Veterinary Clinics
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    • v.26 no.3
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    • pp.200-204
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    • 2009
  • This study was performed to evaluate the effects of reduced L-glutathione on the oxidant/antioxidant status(superoxide dismutase(SOD), catalase(CAT), glutathione peroxidase(GPx), protein carbonyl and lipid hydroperoxide(LPO) concentration), renal function(blood urea nitrogen(BUN) and serum creatinine levels), and microscopy of renal tissues in pigs undergoing unilateral renal ischemia-reperfusion(I/R). Sixteen Landrace and Yorkshire mixed-breed pigs were divided randomly into two groups: untreated control group and reduced L-glutathione-treated group(4 mg/kg IV). Each group had 8 pigs. Pigs were unilaterally nephrectomized and the kidney was subject to 30 min of renal pedicle occlusion. Blood samples for biochemical assay were collected on days 1, 3, 5, 7, and 14 post nephrectomy. Renal I/R injury were evaluated histopathologically by the microscopic observation of renal tissue sections and biochemically by the measurement of the plasma creatinine and urea levels. Parameters of oxidative stress such as SOD, GPx, CAT, protein carbonyl and LPO were measured. The elevation of creatine and BUN levels was lower in the treated group, compared with the control group. The activities of antioxidant-enzyme were higher in the treated group, compared with the control group. In histological findings, the severity of damage in the reduced L-glutathione treated group was less when compared to the control group.

Effect of Yeonsan Ogye bioactive peptides on anti-oxidant indexes in rats' liver

  • Kim, Hye Won;Shim, Jung Hun;Kim, Ki Nam
    • Journal of Nutrition and Health
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    • v.52 no.4
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    • pp.408-411
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    • 2019
  • Purpose: This study investigated the effect of bioactive Yeonsan Ogye peptides (YOPs) intake on changes in the hepatic anti-oxidant indexes in male rats. Methods: Sprague-Dawley male rats were divided into 3 groups and given a casein-based AIN-93G diet and distilled water ad libitum without any added YOPs (control), distilled water with 250 mg of YOPs (Y250), or 500 mg of YOPs (Y500) per kg of body weight for 4 weeks. YOP dose was decided as referred to in the referenced study where toxicity did not occur. The hepatic anti-oxidant indexes were determined using a commercial kit. Statistical analysis was performed using SPSS version 23.0 and are expressed as $mean{\pm}standard$ error of mean. Differences among the groups were evaluated by one-way analysis of variance followed by post hoc Duncan's multiple comparisons test. Results: There were no differences in the body weights, weight gain, food intake, food efficiency ratio, or organ weight, including liver, kidney, spleen, thymus, and epididymal fat, among all of the groups. The hepatic nitric oxide (NO) level in the Y500 group was lower than that in the control and Y250 groups, and the hepatic malondialdehyde (MDA) level was lower in the Y500 group than in the Y250 group. The differences in hepatic superoxide dismutase (SOD) and catalase (CAT) activities were not statistically significant between the groups. From these results we speculated that YOPs may have anti-oxidative abilities to regulate NO and MDA production without affecting SOD and CAT activities. Conclusion: YOPs are presumed to act as anti-oxidants in the animal or human body.

A Study on Factors of Increasing Satisfaction with College Education for Freshmen in College (전문대학 신입생의 대학 교육서비스 만족도 상승 요인에 관한 연구)

  • Lee, Jong-Ha;Han, Sung-il
    • The Journal of the Korea Contents Association
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    • v.21 no.3
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    • pp.390-399
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    • 2021
  • This study analyze the factors that can improve the satisfaction level of college students stable adaptation to college life and education service. It was analyzed whether students' personal characteristics, college life-related characteristics, and changes in college life Adaptation increase the satisfaction of college education service. As a result of analyzing CAT(college adatiation test) differences of 1st survey and 2nd survey in the results of the total 368 students, the graduates of the academic high school showed high academic integration and social integration and the social integration was high in the types of regular admission. As a result of multiple regression analysis with the increase in college education service satisfaction as a dependent variable, the lower the language score, the more positive changes in academic integrity, career identity, college satisfaction, relationship with professors, economic stability, and study keeping stability. Based on these results, various student support programs were proposed to increase the college education service satisfaction of college students.

Beyond Attention-Deficit Hyperactivity Disorder: Exploring Psychiatric Comorbidities and Their Neuropsychological Consequences in Adults

  • Hyun Jae Roh;Geon Ho Bahn;Seung Yup Lee;Yoo-Sook Joung;Bongseog Kim;Eui-Jung Kim;Soyoung Irene Lee;Minha Hong;Doug Hyun Han;Young Sik Lee;Hanik K Yoo;Soo-Young Bhang
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.34 no.4
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    • pp.275-282
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    • 2023
  • Objectives: This study aimed to identify the psychiatric comorbidity status of adult patients diagnosed with attention-deficit hyperactivity disorder (ADHD) and determine the impact of comorbidities on neuropsychological outcomes in ADHD. Methods: The study participants were 124 adult patients with ADHD. Clinical psychiatric assessments were performed by two board-certified psychiatrists in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. All participants were assessed using the Mini-International Neuropsychiatric Interview Plus version 5.0.0 to evaluate comorbidities. After screening, neuropsychological outcomes were assessed using the Comprehensive Attention Test (CAT) and the Korean version of the Wechsler Adult Intelligence Scale, Fourth Edition (K-WAIS-IV). Results: Mood disorders (38.7%) were the most common comorbidity of ADHD, followed by anxiety (18.5%) and substance use disorders (13.7%). The ADHD with comorbidities group showed worse results on the Perceptual Organization Index and Working Memory Index sections of the K-WAIS than the ADHD-alone group (p=0.015 and p=0.024, respectively). In addition, the presence of comorbidities was associated with worse performance on simple visual commission errors in the CAT tests (p=0.024). Conclusion: These findings suggest that psychiatric comorbidities are associated with poor neuropsychological outcomes in adult patients with ADHD, highlighting the need to identify comorbidities in these patients.

Efficacy of Hyeongbangjihwhang-tang on the 5/6 Nephrectomy(NTX) induced Chronic Renal Failure(CRF) Rats (5/6 NTX로 유발된 만성 신부전 랫트에 대한 형방지황탕(荊防地黃湯)의 효과)

  • Ha, Jin-Ho;Choi, Ae-Ryun
    • Journal of Sasang Constitutional Medicine
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    • v.25 no.4
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    • pp.359-372
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    • 2013
  • Objectives The object of this study was to observe the effects of Hyeongbangjihwhang-tang (HB; Soyangin prescription) on the 5/6 NTX induced CRF rats. Methods Each of Hyeongbangjihwhang-tang aqueous extracts 200mg/kg were orally administered once a day for 35 days from 4 weeks after 5/6 NTX surgery. Four groups, each of 8 rats per group were used in this study, were sham group, CRF group, ${\alpha}$-Tocoperol group and HB group. Changes on the left remnant kidney weights, serum BUN, creatinine levels, caspase-3, PARP immunoreactivities were observed to nephroprotective effects, and relative immunomodulatory effects were monitored based on the changes of lymphatic organ weights and splenic cytokine contents. In addition, the changes on the kidney MDA, GSH contents and SOD, CAT activities were also calculated for antioxidant effects, and the effects on the CRF related cachexia were demonstrated based on the changes of body and epididymal fat pad weights, serum TG, TC, LDL and HDL levels. Results and Conclusions 1) HB was significantly decreased the left remnant kidney weights, serum BUN, creatinine levels and caspase-3, PARP immunoreactivities. 2) HB was significantly increased lymphatic organ weights and splenic cytokine contents. 3) HB was significantly increased body and epididymal fat pad weights, and was significantly decreased serum TG, TC, LDL and HDL levels. 4) HB was significantly decreased MDA contents, and was significantly increased GSH contents and SOD, CAT activities. The results obtained in this study suggest that HB significantly retarded immunosuppressions and cachexia related to the 5/6 NTX induced CRF through modulations of oxidative defense systems. Especially HB showed the highest favorable effects more than those of ${\alpha}$-tocoperol.

The Design of Monitoring & Control(M&C) for KUS RFS in KASS (KASS 위성통신국 RF시스템 감시제어장치 설계)

  • Kim, Taehee;Sin, Cheonsig
    • Journal of Satellite, Information and Communications
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    • v.12 no.4
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    • pp.50-55
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    • 2017
  • In this paper, the design of the RF system monitoring and control system of KUS (KASS: KASS Uplink Station) which constitutes KASS (Korea Augmentation Satellite System) is described. The Korean satellite calibration system is named KASS and aims to develop the SBAS system of the APV-1 level SoL service level and the CAT-1 test operation technology. Software and hardware development environment, function and algorithm of supervisory control device, structure of supervisory control device, and user interface were designed to implement KUS / RFS monitoring control device. We have secured the stability and reliability of the system by using the monitoring and control system design of the COMS (Communication Ocean & Meteorological Satellite) and the Korea Satellite 5A / 7 control system, which has already been used for the design of the surveillance control system. In addition, we have made it possible to provide the user interface according to the actual operator's request more conveniently.

Cardiovascular Changes of Cat in Hypothermia (고양이에서 체표냉각에 따른 심혈관계 변동에 관한 연구)

  • Ahn, Young-Soo;Ko, Chang-Mann;Lee, Woo-Choo
    • The Korean Journal of Pharmacology
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    • v.19 no.1
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    • pp.61-69
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    • 1983
  • Hypothermia is an essential preparatory procedure for cardiac surgery, which lows the metabolic rate and myocardial oxygen demand. However, hypothermia itself is a stress enough to change the tonus of sympathoadrenal system, especially the cardiovascular responses to the catecholamines. It is reported that the positive chronotropic and inotropic response of catecholamines is exaggerated during hypothermia because of decreased norepinephrine uptake at the junctional cleft or decreased catecholamine metabolism. On the other hand, there are evidences of diminished catecholamines responses in low temperature ana further, interconversion of adrenergic receptors is also suggested. Present investigation was planned to observe the cardiovascular changes and its responses to catecholamines during surface hypothermia in cat. Healthy mongrel cats, weighing $2{\sim}3\;kg$, anesthetized with secobarbital(30 mg/kg), were permitted to hypothermia by external cooling technic. Esophageal temperature, ECG (lead II), heart rate, left ventricular pressure with dP/dt, carotid artery pressure and left ventricular contractile force were monitored with Polygragh (Model 7, Grass), and the respiration was maintained with artificial respirator (V 5 KG, Narco). Followings are summarized results. 1) Surface cooling caused progressive decrease of body temperature and reached $l8.8{\pm}0.8^{\circ}C$ and $16.9{\pm}0.6^{\circ}C$ in 120 and 150 min respectively, after immersion into ice water, and ventricular fibrillation was developed at $20.4{\pm}0.65^{\circ}C$. 2) Heart rate, blood pressure and myocardial contractility were decreased after initial increase as the body temperature falls. 3) Systolic and diastolicdd P/dt of left ventricular pressure were decreased and that the decrement of diastolic dP/dt was more marked. 4) On ECG, ST depression, Twave inversion and prolongation of PR interval were prominent in hypothermia, and moreover, the prolongation of PR interval was marked just prior to the development of ventricular fibrillation. 5) The cardiovascular responses to catecholamines, especially to isoproterenol, were suppressed under hypothermia.

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Effect of probiotics Lactobacillus paracasei GKS6, L. plantarum GKM3, and L. rhamnosus GKLC1 on alleviating alcohol-induced alcoholic liver disease in a mouse model

  • Tsai, You-Shan;Lin, Shih-Wei;Chen, Yen-Lien;Chen, Chin-Chu
    • Nutrition Research and Practice
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    • v.14 no.4
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    • pp.299-308
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    • 2020
  • BACKGROUND/OBJECTIVES: Heavy alcohol consumption causes the development of alcoholic liver disease (ALD), a neglected but important public health problem. Many studies have pointed out that probiotics could improve gut health, which is also considered to be a cause of ALD. Therefore, this study screened the probiotics, Lactobacillus casei GKC1 (GKC1), L. fermentum GKF3 (GKF3), Bifidobacterium lactis GKK2 (GKK2), L. rhamnosus GKLC1 (GKLC1), L. paracasei GKS6 (GKS6), and L. plantarum GKM3 (GKM3), for their potential benefits in alleviating ALD for applications to disease prevention. SUBJECTS/METHODS: C57BL/6N mice were divided into 8 groups (n = 6 in each): normal control, positive control (alcohol-diet fed), and treatments of feeding probiotics GKC1, GKF3, GKK2, GKLC1, GKS6, and GKM3 under an oral dose 0.82 g/kg B.W. per day by oral gavage. The experiment was conducted for 8 weeks, and the concentrations of alanine aminotransferase (ALT), aspartate aminotransferase, triglyceride (TG), and total cholesterol (TC) in mice were measured. The glutathione (GSH), catalase (CAT), and histology were analyzed after sacrifice. RESULTS: The results showed a decrease in the serum ALT, liver TG, and liver TC levels in the GKS6, GKM3, and GKLC1 groups compared to the positive control. In addition, the decreasing GSH and CAT levels were inhibited in the GKS6 and GKM3 groups. The histopathological results showed that all probiotics could reduce the accumulation of liver fat. Furthermore, there was a significant difference in GKLC1 with lower stomach damage compared to the alcohol-fed mice without any addition of probiotics. CONCLUSIONS: GKLC1, GKS6, and GKM3 can be used as supplements for alleviating the development of ALD.