• Title/Summary/Keyword: MG-132

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Cytosolic prion protein induces apoptosis in human neuronal cell SH-SY5Y via mitochondrial disruption pathway

  • Wang, Xin;Dong, Chen-Fang;Shi, Qi;Shi, Song;Wang, Gui-Rong;Lei, Yan-Jun;Xu, Kun;An, Run;Chen, Jian-Ming;Jiang, Hui-Ying;Tian, Chan;Gao, Chen;Zhao, Yu-Jun;Han, Jun;Dong, Xiao-Ping
    • BMB Reports
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    • v.42 no.7
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    • pp.444-449
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    • 2009
  • Different neurodegenerative disorders like prion disease, is caused by protein misfolding conformers. Reverse-transfected cytosolic prion protein (PrP) and PrP expressed in the cytosol have been shown to be neurotoxic. To investigate the possible mechanism of neurotoxicity due to accumulation of PrP in cytosol, a PrP mutant lacking the signal and GPI (CytoPrP) was introduced into the SH-SY5Y cell. MTT and trypan blue assays indicated that the viability of cells expressing CytoPrP was remarkably reduced after treatment of MG-132. Obvious apoptosis phenomena were detected in the cells accumulated with CytoPrP, including loss of mitochondrial transmembrane potential, increase of caspase-3 activity, more annexin V/PI-double positive-stained cells and reduced Bcl-2 level. Moreover, DNA fragmentation and TUNEL assays also revealed clear evidences of late apoptosis in the cells accumulated CytoPrP. These data suggest that the accumulation of CytoPrP in cytoplasm may trigger cell apoptosis, in which mitochondrial relative apoptosis pathway seems to play critical role.

Differential Expression and Stability of Endogenous Nuclear Factor E2-related Factor 2 (Nrf2) by Natural Chemopreventive Compounds in HepG2 Human Hepatoma Cells

  • Jeong, Woo-Sik;Keum, Young-Sam;Chen, Chi;Jain, Mohit R.;Shen, Guoxiang;Kim, Jung-Hwan;Li, Wenge;Kong, Ah-Ng Tony
    • BMB Reports
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    • v.38 no.2
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    • pp.167-176
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    • 2005
  • Nuclear factor-E2-related factor 2 (Nrf2) is known as a key regulator of ARE-mediated gene expression and the induction of Phase II detoxifying enzymes and antioxidant enzymes, which is also a common property of many chemopreventive agents. In the present study, we investigated the regulatory role of different chemopreventive agents including sulforaphane (SUL), allyl isothiocyanate (AITC), indole-3-carbinol (I3C), and parthenolide (PTL), in the expression and degradation of Nrf2 and the induction of the antioxidant enzyme HO-1. SUL strongly induced Nrf2 protein expression and ARE-mediated transcription activation, retarded degradation of Nrf2 through inhibiting Keap1, and thereby activating the transcriptional expression of HO-1. AITC was also a potent inducer of Nrf2 protein expression, ARE-reporter gene and HO-1 but had little effect on delaying the degradation of Nrf2 protein. Although PTL and I3C could induce ARE reporter gene expression and Nrf2 to some extent, they were not as potent as SUL and AITC. However, PTL dramatically induced the HO-1 expression, which was comparable to SUL, while I3C had no effect. In addition, when treated with SUL and PTL, inhibition of proteasome by MG132 did not cause additional accumulation of Nrf2, suggesting the involvement of other degradation mechanism(s) in the presence of these compounds such as SUL and PTL. In summary, the results of our current study indicated that different chemopreventive compounds have different regulatory properties on the accumulation and degradation of Nrf2 as well as the induction of cellular antioxidant enzyme HO-1.

Effects of Naloxone on Morphine Analgesia and Spinal c-fos Expression in Rat Formalin Test (Naloxone이 흰쥐 Formalin Test에서 Morphine의 진통효과와 척수 c-fos 유전자 발현에 미치는 영향)

  • Song, Sun Ok;Seok, Je Hong;Lee, Deok Hee;Park, Dae Pal;Kim, Seong Yong;Lim, Jeong Sook;Song, Sun Kyo;Lee, Nam Hyuk
    • The Korean Journal of Pain
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    • v.18 no.2
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    • pp.124-132
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    • 2005
  • Background: This study was performed to evaluate the dose-related effects of naloxone on morphine analgesia in the rat formalin test, and observe the correlation of pain behavior and spinal c-fos expression induced by a formalin injection. Methods: Fifty rats were divided into five groups; control, morphine (morphine pre-treated, intra-peritoneal injection of 0.1 mg of morphine 5 min prior to formalin injection), and three naloxone groups, which were divided according to the administered dose-ratio of naloxone to morphine 20 : 1 ($5{\mu}g$), 10 : 1 ($10{\mu}g$), and 1 : 1 ($100{\mu}g$) representing the low-, medium-, and high-dose naloxone groups, respectively, were injected intra-peritoneally 16 min after a formalin. A fifty ul of 5% formalin was injected into the right hind paw. All rats were observed for their pain behavior according to the number of flinches during phases 1 (2-3, 5-6 min) and 2 (1 min per every 5 min from 10 to 61 min). The spinal c-fos expression was quantitatively analyzed at 1 and 2 hours after the formalin injection using a real-time PCR. Results: The morphine pre-treated (morphine and three naloxone) groups during phase 1, and the morphine, low- and medium-dose naloxone groups during phase 2, showed significantly less flinches compared to those of the control (P < 0.05). In the three naloxone groups, the numbers of flinches were transiently reduced following the naloxone injection in the low- and medium-dose groups compared to those of the morphine group (P < 0.05). The duration of the reduced flinches was longer in the medium-dose group (P < 0.05). The high-dose group revealed immediate increases in flinches immediately after the naloxone injection compared to those of the morphine, low- and medium-dose groups (P < 0.05 for each). The spinal c-fos expression showed no significant patterns between the experimental groups. Conclusions: Our data suggest that relatively low-dose naloxone (1/20 to 1/10 dose-ratio of morphine) transiently potentiates morphine analgesia; whereas, high-dose (equal dose-ratio of morphine) reverses the analgesia, and the spinal c-fos expression does not always correlate with pain behavior in the rat formalin test.

A Study on Soil Contamination of Children's Parks within the Gyeonggi-do Province Area (경기도내 어린이공원의 토양오염실태 연구)

  • Kim, Woongsoo;Song, Ilseok;Shin, Jonghyun;Oh, Cheonhwan;Kim, Eunah;Kim, Keugtae;Kim, Hyunja;Kim, Jongsu;Choi, Yunho
    • Journal of Environmental Health Sciences
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    • v.43 no.3
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    • pp.233-239
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    • 2017
  • Objectives: The pollution status of heavy metals within the soil was investigated with an aim to establishing a sustainable soil environment within parks and amusement facilities installed in urban areas of Gyeonggi-do Province. Methods: As sampling sites, 14 locations were selected from a city with a number of factories near a residential area, a residential area, and a children's park in a city with mixed green areas. Seven kinds of heavy metals, including Cd, Pb, and Hg, and the pH of soil were analyzed three times by inductively coupled plasma optical emission spectroscopy (ICP-OES) and atomic absorption spectrometer (AAS). Results: In this study, the pH of the samples from the residential park and industrial park showed 5.7-6.5 and 5.9-7.0, respectively. The overall mean concentration (mg/kg) of heavy metals was Zn (132.8), Ni (73.0), Cu (47.4), Pb (35.9), As (4.84), Cd (0.39), and Hg (0.07), indicating that these concentrations of heavy metals were lower than those for the area 1 standard of soil pollution concern criteria. In addition, the sampling sites in the residential area and the industrial area also showed the same tendency for concentration distribution. Conclusions: We found that the soil pollution class (SPC) of some spots were over 200, which are third and fourth classes. In order to manage a sustainable soil environment in a city park, it is suggested that local governments, the management bodies for these parks, need to manage, supervise, and investigate soil pollution and quickly replace contaminated soil.

Berchemia floribunda-mediated Proteasomal Degradation of CyclinD1 via GKS3β-dependent Threonine-286 Phosphorylation in Human Colorectal Cancer Cells (인간 대장암 세포에 대한 먹넌출 추출물의 GSK3β 의존성 threonine-286 인산화를 통한 Cyclin D1 분해)

  • Kang, Yeongyeong;Eo, Hyun Ji;Kim, Da Som;Park, Youngki;Song, Jeong Ho;Park, Gwang Hun
    • Korean Journal of Plant Resources
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    • v.33 no.4
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    • pp.271-278
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    • 2020
  • In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of the Berchemia floribunda (BF) which belongs to Rhamnaceae against human colorectal cancer cells. The treatment of BF decreased the cell proliferation in HCT116 cell and suppressed cellular accumulation of Cyclin D1 protein. Inhibition of proteasomal activity by MG132 attenuated BF-mediated Cyclin D1 downregulation and Cyclin D1 was decreased in the cell treated with BF. These findings indicates that BF-mediated Cyclin D1 downregulation may be result from Cyclin D1 proteasomal degradation. Additionally, BF-mediated Cyclin D1 degradation was blocked in the presence of LiCl, a GSK3β inhibitor, but not PD98059, SP600125, SB203580, Bay11-7082, LY294002 an ERK1/2 inhibitor, JNK inhibitor, p38 inhibitor, IκK inhibitor and PI3K inhibitor. Furthermore, BF phosphorylated Cyclin D1 at threonine-286 (Thr286), and LiCl-induced GSK3β inhibition reduced the BF mediated phosphorylation of Cyclin D1 at Thr286. These results suggested that BF may downregulate Cyclin D1 expression as a potential anti-cancer target through GSK3β dependent Cyclin D1 degradation. Therefore, this study provides that the extract of BF has anticancer activity against human colorectal cancer cells.

Clinical Trial to Evaluate the Efficacy of Extract of Citri Pericarpium on Serum Lipid Profiles in Subjects: a Randomized, Double-blind (혈중지질에 대한 진피추출물의 유효성 평가를 위한 인체적용시험 : 무작위배정, 이중맹검)

  • Lee, Jin-Sang;Do, Eun-Ju;Kwak, Min-A;Park, Hyun-Jin;Ha, Il-Do;Sung, Ki-Jun;Kim, Mi-Ryeo
    • The Korea Journal of Herbology
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    • v.26 no.1
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    • pp.125-132
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    • 2011
  • Objectives : This study was performed to evaluate the efficacy of extract from Citri Pericarpium (CP) on lipid-lowering effect in semi-healthy subjects with increased serum levels of total cholesterol and triglyceride. Methods : A experimental group (n=45) and placebo group (n=46) were randomly established based on the plasma lipid profiles (triglyceride, total cholesterol etc.) in the semi-healthy subjects, then all subjects randomly took experimental or placebo capsules, which contain 1,200 mg of CP or the same dose of soluble starch per day with regular meals for 8 weeks by double-blind method. Results : One-hundred forty (140) subjects were screened, then 91 subjects enrolled in the study. No serious adverse events were reported for trial period. The CP treatment showed statistically significant decrease in serum levels of triglyceride both at 4-weeks (p<0.01) and at 8-weeks (p=0.0001). Futhermore, there was significant difference in the triglyceride levels between CP-treated and placebo group. The CP-treated but not placebo group, experienced decrease in serum levels of total cholesterol at 8-weeks. Then there was no significant difference in the total cholesterol levels between the two groups. In addition, statistically significant difference of AST, ALT, ${\gamma}$-GT serum levels wasn't shown before and after trial in two groups. Conclusion : These results demonstrate that CP can significantly suppress the elevated triglyceride but not total cholesterol level. Therefore, CP may play a role in the improvement of blood lipid levels, as an effective functional food.

The Study on the Sweating Responses of Adult Female according to Garment types (의복형태에 따른 성인여성의 발한반응에 관한 연구)

  • Yeom Hee Gyong;Choi Jeong Wha
    • Journal of the Korean Society of Clothing and Textiles
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    • v.16 no.4 s.44
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    • pp.405-416
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    • 1992
  • This study was performed to investigate correlation between total body weight loss and local sweat rate and to find out any possible method that can estimate total body weight loss judging from local sweat rate. Twelve adult females were kept at 44 $\pm1^{\circ}C$, 50 ${\pm}5\%$ R.H. (1) Physiological responses such as total body weight loss, local sweat rate, rectal temperature, skin temperature, blood pressure and pulse, (2) micro climate inside garment and (3) subjective sensation were examined. Two types of garment such as long-sleeves with long pants (Type I) and half·sleeves with short pants (Type II) were used to observe the effect of garment types on sweating response. Both clothing weight was equal (132$\pm$3 g/$m^{2}$). The results were as follows: 1. Regardless of the different types, total body weight loss was more interrelated with the sweat rate on forehead than any other parts of the body. Except the forehead, different parts of body with different types of garment influenced on body weight loss quite differently. 2. Total body weight loss was more interrelated with the weight gain of garment than the local sweat rate. 3. Under the environment of 44$\pm1^{\circ}C,\;50{\pm}5\%$R.H., body weight loss during 1 hour of subject clothed and silted was 275.2 g/hr and weight loss per body surface area was 178.9 g/$m^{2}/hr$ Garment types have no influences on total body weight loss. 4. Local sweat rate (mg/7.07 $cm^{2}/hr$) was 208.0,191.0, 133.0, 115.0,81 0, 75.1 and 66.3 on scruff, breast, forehead, forearm, thigh, upper arm, leg respectively No evidence has been found that garment types influenced on local sweat rate (p<0.1). 5. No interrelationships between rectal temperature and total body weight loss, local skin temperature and total body weight loss, and local skin temperature and local sweat rate were found. From this study, some possible method that we can estimate total body' weight loss judging from weight loss of garment. But considering the fact that clothing design factor, the physical characteristics of fabric and environmental factor such as humidity and wind velocity should be concerned in weight loss of garment, it should be studied further whether the total body weight loss can be estimated properly from the weight loss of garment. This experiment suggest that different parts of body with different types of garment can influence on body weight loss quite differently. Therefore, in order to get more precise results, more studies under the diversity of garment types should be done in the near future.

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Effects of Application of Liquid Pig Manure on Green Manure Crop Triticale and Subsequent Soil Quality (돈분액비 시용이 트리티케일 생육과 토양의 화학적 특성에 미치는 영향)

  • Lee, Byung-Jin;Kim, Kyeong-Mok;Chun, Hyun-Sik;Jeon, Seung-Ho;Cho, Young-Son
    • Korean Journal of Organic Agriculture
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    • v.22 no.2
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    • pp.293-302
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    • 2014
  • As part of the agricultural natural circulation, the present study was performed. Recently, there has been the movement toward reusing the Liquid Pig Manure as an alternative fertilizer sources for agricultural lands. For instance, LPM (Liquid Pig Manure) liquid fertilizer has been developed and widely used in Korea. However, the impacts of LPM on both agricultural environment and crop triticale yield have not been investigated yet. The experiments were studied on paddy field after treatment of LPM on plant height, root length, plant length, dry matter yield and soil chemical properties. The effect of LPM by application on triticale was more increased plant height, root length and plant length than the Control. Chemical soil characteristics were not significantly different between on Control and LPM. Soil pH, OM, TN, $P_2O_5$ and exchangeable cation of triticale (X Triticosecale wittmack) appeared to be lower than before the treatment. Dry matter yield were produced 834.3kg $10a^{-1}$ of in LPM plot and 684.4kg $10a^{-1}$ in Control plot. In these results show abbreviated as the application of LPM increases the yield index of triticale. However, the properties of paddy soil were not affected by the LPM application.

Evaluation of Coronary Artery Disease with Gated Blood Pool Scan Using Dipyridamole (Dipyridamole 부하 심장 풀 스캔을 이용한 관동맥질환의 평가)

  • Kim, Gwang-Weon;Choi, Chung-Il;Chung, Byung-Cheon;Lee, Jae-Tae;Lee, Kyu-Bo;Chae, Shung-Chull;Jun, Jae-Eun;Park, Wee-Hyun;Park, Hee-Myung
    • The Korean Journal of Nuclear Medicine
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    • v.25 no.1
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    • pp.27-36
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    • 1991
  • Thirty-one patients with coronary artery disease and twenty-sir normal subjects underwent $^{99m}Tc-GBPS$ before and after coronary vasodilatation was induced by dipyridamle 0.54 mg/kg given IV over 4 min. LVEF, ${\Delta}EF$ and regional wall motion by phase analysis were measured during rest and dipyridamole infusion. The results were as follows: 1) Mean LVEF of normal subjects was significantly higher than that of MI group (p=0.001), but similar to that of angina group during rest. Among MI group, mean LVEF of anterior MI group was significantly lower than that of inferior MI group during rest (p=0.024). 2) The normal subjects had a significaat increase in mean LVEF during dipyridamole infusion $(+12{\pm}3.8)$, while the CAD group had no increase $(+2{\pm}5.0)$ (p<0.001). If an increase of LVEF during stress is less than 5%, it suggests an abnormality. The sensitivity and specificity of LVEF changes after dipyridamole infusion were 81%, 96%, respectively. 3) With phase analysis, LV mean phase angle of normal subjects and CAD patients was $143{\pm}20.5^{\circ},\;132{\pm}20.6^{\circ}$ respectively, durign rest (p=0.049). But an ncrease of LV mean phase angle during dipyridamole infusion in these two groups was not significantly different. Dipyridamole infusion did not affect standard deviation and FWHM of phase angle. 4) Regional wall motion was abnormal in 5 patients (16%) during dipyridamole infusion. 5) Side effects with dipyridamole infusion include; headache, angina pain, chest discomfirt, nausea, weakness sense. In conclusion, dipyridamole GBPS might be useful in detection and follow up of CAD.

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Molecular Analysis of Bacterial Communities Distributed in Sea Water of Whitening Areas of Jeju Coast (제주연안 갯녹음(백화) 지역의 해수에 분포하는 세균군의 분자생물학적 분석)

  • 강형일;강봉조;김미란;윤병준;이동헌;오덕철
    • Korean Journal of Microbiology
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    • v.38 no.2
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    • pp.127-132
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    • 2002
  • In this study, the bacterial communities distributed in sea water of the whitening areas of Gangjeong and Seongsan, Jeju-do have been analysed using the PCR amplification of 16S rRNA to obtain fundamental data and information on relationship of the whitening phenomenon and microbial ecosystem. In Gangjeong, diverse bacteria such as Alcanivorax, Paracoccus, Damselae, Pseudomonas, Rhodowlum, Silicibacter, Suiftobacter, and Roseobacter have been found, and Alcanivorax was the most abundant clone. The most abundant clone from Seongsan was Pseudomonas, of which Pseudomonas tolaasii and Pseudomonas mandeli were most abundantly occurred in the frequency of approx44% and 24%, respectively. Approx4% of the bacterial clones closest to Verrucomicrobiales and other unidentified clones were also fecund in Seongsan, suggesting there is a great discrepancy between bacterial communities from the whitening areas of Seongsan and Gangjeong. The mean temperature, chlorine concentration, pH, and dissolved oxygen (DO) of the sea water of Gangieong and Seongsan in August of 2001 (sampling period) was $27^{\circ}C$~$27.5^{\circ}C$, 30.24~30.60%, pH 8.23~8.36,7 .20~7.28 mg/ι, suggesting other environmental factors except far the factors mentioned above might result in difference of bacterial communities distributed in both areas.