• Title/Summary/Keyword: PEP-1

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PEP-1-p18 prevents neuronal cell death by inhibiting oxidative stress and Bax expression

  • Kim, Duk-Soo;Sohn, Eun-Jeong;Kim, Dae-Won;Kim, Young-Nam;Eom, Seon-Ae;Yoon, Ga-Hyeon;Cho, Sung-Woo;Lee, Sang-Hyun;Hwang, Hyun-Sook;Cho, Yoon-Shin;Park, Jin-Seu;Eum, Won-Sik;Choi, Soo-Young
    • BMB Reports
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    • v.45 no.9
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    • pp.532-537
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    • 2012
  • P18, a member of the INK4 family of cyclin-dependent kinase inhibitors, is a tumor suppressor protein and plays a key cell survival role in a variety of human cancers. Under pathophysiological conditions, the INK4 group proteins participate in novel biological functions associated with neuronal diseases and oxidative stress. Parkinson's disease (PD) is characterized by loss of dopaminergic neurons, and oxidative stress is important in its pathogenesis. Therefore, we examined the effects of PEP-1-p18 on oxidative stress-induced SH-SY5Y cells and in a PD mouse model. The transduced PEP-1-p18 markedly inhibited 1-methyl-4-phenyl pyridinium-induced SH-SY5Y cell death by inhibiting Bax expression levels and DNA fragmentation. Additionally, PEP-1-p18 prevented dopaminergic neuronal cell death in the substantia nigra of a 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine-induced PD mouse model. These results indicate that PEP-1-p18 may be a useful therapeutic agent against various diseases and is a potential tool for treating PD.

Protective effects of PEP-1-Catalase on stress-induced cellular toxicity and MPTP-induced Parkinson's disease

  • Eom, Seon Ae;Kim, Dae Won;Shin, Min Jea;Ahn, Eun Hee;Chung, Seok Young;Sohn, Eun Jeong;Jo, Hyo Sang;Jeon, Su-Jeong;Kim, Duk-Soo;Kwon, Hyeok Yil;Cho, Sung-Woo;Han, Kyu Hyung;Park, Jinseu;Eum, Won Sik;Choi, Soo Young
    • BMB Reports
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    • v.48 no.7
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    • pp.395-400
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    • 2015
  • Parkinson's disease (PD) is a neurodegenerative disability caused by a decrease of dopaminergic neurons in the substantia nigra (SN). Although the etiology of PD is not clear, oxidative stress is believed to lead to PD. Catalase is antioxidant enzyme which plays an active role in cells as a reactive oxygen species (ROS) scavenger. Thus, we investigated whether PEP-1-Catalase protects against 1-methyl-4-phenylpyridinium (MPP+) induced SH-SY5Y neuronal cell death and in a 1-methyl-4-phenyl-1,2,3,6-trtrahydropyridine (MPTP) induced PD animal model. PEP-1-Catalase transduced into SH-SY5Y cells significantly protecting them against MPP+-induced death by decreasing ROS and regulating cellular survival signals including Akt, Bax, Bcl-2, and p38. Immunohistochemical analysis showed that transduced PEP-1-Catalase markedly protected against neuronal cell death in the SN in the PD animal model. Our results indicate that PEP-1-Catalase may have potential as a therapeutic agent for PD and other oxidative stress related diseases. [BMB Reports 2015; 48(7): 395-400]

Transduced PEP-1-AMPK inhibits the LPS-induced expression of COX-2 and iNOS in Raw264.7 cells

  • Shin, Min-Jea;Lee, Yeom-Pyo;Kim, Dae-Won;An, Jae-Jin;Jang, Sang-Ho;Cho, Sung-Min;Sheen, Seung-Hoon;Lee, Hae-Ran;Kweon, Hae-Yong;Kang, Seok-Woo;Lee, Kwang-Gill;Park, Jin-Seu;Eum, Won-Sik;Cho, Yong-Jun;Choi, Soo-Young
    • BMB Reports
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    • v.43 no.1
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    • pp.40-45
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    • 2010
  • AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme that plays a central role in cellular metabolic stress. Modulation of nitric oxide (NO) and cyclooxygenase-2 (COX-2) is considered a promising approach for the treatment of inflammation and neuronal diseases. In this study, the AMPK gene was fused in-frame with PEP-1 peptide in a bacterial expression vector to produce a PEP-1-AMPK fusion protein. Expressed and purified PEP-1-AMPK fusion proteins were transduced efficiently into macrophage Raw 264.7 cells in a time- and dose-dependent manner. Furthermore, transduced PEP-1-AMPK fusion protein markedly inhibited LPS-induced iNOS and COX-2 expression. These results suggest that the PEP-1-AMPK fusion protein can be used for the protein therapy of COX-2 and NO-related disorders such as inflammation and neuronal diseases.

Cardiac systolic time intervals and heather index measured by impedance cardiography during postural changes (체위변화시 심장의 수축기 시간간격 및 Heather Index의 변화)

  • 고성경;김창규;김덕원
    • Journal of the Ergonomics Society of Korea
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    • v.11 no.1
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    • pp.67-79
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    • 1992
  • Cardiac systolic time intervals (STLs) and Heather index (HI) were used to access changes in left ventricular function of six male subjects exposed to postural changes,$0^{\circ}C$, ${\pm}2^{\circ}C$, ${\pm}45^{\circ}C$, ${\pm}90^{\circ}C$, Significant prolongation of the pre-ejection period (PEP) and PEP/ LVET ratio, shortening of the left ventricular ejection time (LVET), STI, HI and $1/PEP^{2}$were observed during exposure to both $+45^{\circ}C $ and $+90^{\circ}C $But the values measured during $-45^{\circ}C $ and$-90^{\circ}C $ were reversed. Changes in fluid shift, filling volume, preload, after load and sympathetic activities may account for the observed findings. Early response of cardiac foctions was recorded using impedance cardiography. This method is very simple but accurate. Thus it will be useful in this aerospace and work physiology. In conclusion, STIs appear to provide reliable noninvasive method for examining changes of cardiac function during exposure to postural changes.

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Clinical Correlation between the Serum Pepsinogen I/II Ratio and Gastric Cancer (위암환자에서 혈중 Pepsinogen 검사의 의미)

  • Ahn, Dae-Ho;Kang, Hae-Yoon;Kim, Kang-Il;Kim, Se-Hyun;Hong, Sung-Pyo
    • Journal of Gastric Cancer
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    • v.5 no.3 s.19
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    • pp.158-162
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    • 2005
  • Purpose: In order to clarify the carcinogenesis mechanism from chronic atrophic gastritis toward gastric cancer, we measured the pepsinogen I and II and compared their ratio with several clinical findings. Materials and Methods: We measured the preoperative serum pepsinogen I and II by using a radio-immunoassay and compared their ratio with several clinical findings, such as tumor size, mucinous vs non-mucinous tumor, cell differentiation, tumor location, depth of invasion, lymph-node status, Lauren's classification, and peritumoral atrophy in 103 consecutive patients with gastric adenocarcinomas who had received resections at Bundang CHA Hospital during the period from July 2003 to February 2005. Results: There were significant differences in the serum pepsinogen I/II ratio between patients with mucinous vs non-mucinous tumors (n=4 vs 9 and mean pep I/II=1.29 vs. 2.99, p=0.0288), with tumor size more than and less than $10cm^2$ (n=55 vs. 48 and mean pep I/II=2.64 vs. 3.24, p=0.0491), and with or without peritumoral atrophy (n=94 vs. 9 and mean pep I/II=2.83 vs. 3.89, p=0.0466). In patients with peritomoral atrophy, the pepsinogen I/II ratio was also lower in larger tumors (n=48 vs. 46 and mean pep I/II=2.44 vs. 3.23, p=0.0083). Well-differentiated carcinomas showed significantly lower serum pep I/II ratios than signet-ring-ceil types. There was no correlation between serum pep I/II ratio and tumor location, depth of invasion, lymph-node status, or Lauren's classification Conclusion: We proved the existence of a correlation between serum pepsinogen level and musosal atrophy, but these results are not sufficient for clinical application of serum pepsinogen level as a screening tool for gastric cancer.

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A Study on the Evaluation of Pro-environmental Potential of Streams in Sunchon City (중.소도시 하천의 친환경적 활용 잠재력 평가에 관한 연구 -전남 순천시 하천을 사례로-)

  • 정정채;이상석
    • Journal of the Korean Institute of Landscape Architecture
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    • v.26 no.1
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    • pp.96-112
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    • 1998
  • This study aims to evaluate the potential of pro-environmental application(PEP) in streams conceptualized ecological conservation and recreational use to be in harmony with. The main content of research are to clarify the PEP, to establish the evaluation model, and to evaluate 3 streams(Dongchon, Seokhyunchon, Okchon) in Sunchon city. Researchers introduced 12 evaluation items(water quality, water quantity, vegetation-water area, vegetation conservation, streamscape, neighborhood landscape, stream width, optimum area, nearby landuse, facility in stream, distance from user, obstacle to acces) by 5 scales to evaluate the characteristics of natural and artificial factors in stream area and nearby area. Also to decide the weight of items, researchers surveyed the opinion of 22 landscape architects experienced stream-plan through delphi method. Lastly the pro-environmental potential on streams were calculated by the ecological potential and recreational potential indices to be standardized and indicidual sections in streams were divided 5 grades on the basis of PEP. The result of this study are as follows; 1) The evaluation model of PEP was constructed by 4 steps, such as the decision of weight, the measurement of scale, the calculation of potential indices, the gradation of individual sections in streams. 2) The ecological potential were highly influenced by natural factor such as water quality, vegetation conservation, vegetation-water area, but on the other hand the recreational potential were influenced by optimum area, distance from user, water quantity, obstacle to access. 3) The factors such as vegetation conservation, optimum area, nearby landuse, distance from user were function as discernment factors to evaluate relatively ecological and recreational potential. and water quality, water quantity, vegetation -water area, neighborhood landscape were acted as important items to decide PEP.

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Effect of Memory-enhancing Herbal Extract (YMT_02) on Modulating Pentraxin, PEP-19 and Transthyretin gene Expression in Rat Hippocampus (육미지황탕가미방에 의한 흰쥐 기억력 향상과 관련된 Hippocampus 부위의 특이 유전자 발현에 대한 연구)

  • Sim Dea Sik;Rho Sam Woong;Lee Jin Woo;Lee Eun A;Cho Chong Woon;Bae Hyun Su;Shin Min Kyu;Hong Moo Chang
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.3
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    • pp.684-692
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    • 2003
  • The herbal extract(YMT_02) is a modified extracts from Yukmijihwang-tang(YMJ) to promote memory-enhancing. The YMJ extracts has been widely used as replenishing yin and tonifying the kidneys herbal medicine for hundred years ia Asian countries. The purpose of this study is to: 1) quantitatively evaluate the memory-enhancing effect of YMT_02 by passive avoidance test, 2) statistical evaluation of candidate gene expression (pentraxin. PEP-19, transthyretin) in rat hippocampus. The hippocampi of YMT_02 and control group were dissected and mRNA was further purified. After synthesizing cDNA using oligo-dT primer, the cDNA were applied to Real Time PCR. The results were as follows : 1) passive avoidance test showed enhancing memory retentin by YMT_02 treatment, 2) expression of pentraxin, that accelerate degenerating of neuronal cell, was significantly decreased, 3) the mRNA of genes that has been known to be associated with protecting neuronal cell degeneration, such as PEP-19 and transthyretin, were significantly increased upon YMT_02 treatment. From above results, the administration of YMT_02 which tonify the function of Kidneys could enhance the ability of memory and learning. In addition, the administration of YMT_02 enhance memory retention through modulating particular gene (pentraxin, PEP-19, transthyretin) expressions in hippocampu.

The effects of PEP-1-FK506BP on dry eye disease in a rat model

  • Kim, Dae Won;Lee, Sung Ho;Ku, Sae Kwang;Lee, Ji Eun;Cha, Hyun Ju;Youn, Jong Kyu;Kwon, Hyeok Yil;Park, Jong Hoon;Park, Eun Young;Cho, Sung-Woo;Han, Kyu Hyung;Park, Jinseu;Eum, Won Sik;Choi, Soo Young
    • BMB Reports
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    • v.48 no.3
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    • pp.153-158
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    • 2015
  • As FK506 binding proteins (FK506BPs) are known to play an important role in the regulation of a variety of biological processes related to cell survival, this study was designed to examined the protective effects of FK506 binding protein 12 (FK506BP) on low humidity air flow induced dry eye in a rat model using transduced PEP-1-FK506BP. After the topical application of PEP-1-FK506BP, tear volumes were markedly increased and significant prevention of cornea damage was observed compared with dry eye rats. Further, immunohistochemical analysis demonstrated that PEP-1-FK506BP markedly prevented damage to the cornea, the bulbar conjunctiva, and the palpebral conjunctiva epithelial lining compared with dry eye rats. In addition, caspase-3 and PARP expression levels were found to be decreased. These results demonstrated that topical application of PEP-1-FK506BP significantly ameliorates dry eye injury in an animal model. Thus, we suggest that PEP-1-FK506BP can be developed as a new ophthalmic drop to treat dry eye diseases.

PEP-1-FK506BP inhibits alkali burn-induced corneal inflammation on the rat model of corneal alkali injury

  • Kim, Dae Won;Lee, Sung Ho;Shin, Min Jea;Kim, Kibom;Ku, Sae Kwang;Youn, Jong Kyu;Cho, Su Bin;Park, Jung Hwan;Lee, Chi Hern;Son, Ora;Sohn, Eun Jeong;Cho, Sung-Woo;Park, Jong Hoon;Kim, Hyun Ah;Han, Kyu Hyung;Park, Jinseu;Eum, Won Sik;Choi, Soo Young
    • BMB Reports
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    • v.48 no.11
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    • pp.618-623
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    • 2015
  • FK506 binding protein 12 (FK506BP) is a small peptide with a single FK506BP domain that is involved in suppression of immune response and reactive oxygen species. FK506BP has emerged as a potential drug target for several inflammatory diseases. Here, we examined the protective effects of directly applied cell permeable FK506BP (PEP-1-FK506BP) on corneal alkali burn injury (CAI). In the cornea, there was a significant decrease in the number of cells expressing pro-inflammation, apoptotic, and angiogenic factors such as TNF-α, COX-2, and VEGF. Both corneal opacity and corneal neovascularization (CNV) were significantly decreased in the PEP-1-FK506BP treated group. Our results showed that PEP-1-FK506BP can significantly inhibit alkali burn-induced corneal inflammation in rats, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors and inflammatory cytokines. These results suggest that PEP-1-FK506BP may be a potential therapeutic agent for CAI.

Transduced Human Copper Chaperone for Cu,Zn-SOD (PEP-1-CCS) Protects Against Neuronal Cell Death

  • Choi, Soo Hyun;Kim, Dae Won;Kim, So Young;An, Jae Jin;Lee, Sun Hwa;Choi, Hee Soon;Sohn, Eun Jung;Hwang, Seok-Il;Won, Moo Ho;Kang, Tae-Cheon;Kwon, Hyung Joo;Kang, Jung Hoon;Cho, Sung-Woo;Park, Jinseu;Eum, Won Sik;Choi, Soo Young
    • Molecules and Cells
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    • v.20 no.3
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    • pp.401-408
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    • 2005
  • Reactive oxygen species (ROS) contribute to the development of various human diseases. Cu,Zn-superoxide dismutase (SOD) is one of the major means by which cells counteract the deleterious effects of ROS. SOD activity is dependent upon bound copper ions supplied by its partner metallochaperone protein, copper chaperone for SOD (CCS). In the present study, we investigated the protective effects of PEP-1-CCS against neuronal cell death and ischemic insults. When PEP-1-CCS was added to the culture medium of neuronal cells, it rapidly entered the cells and protected them against paraquat-induced cell death. Moreover, transduced PEP-1-CCS markedly increased endogenous SOD activity in the cells. Immunohistochemical analysis revealed that it prevented neuronal cell death in the hippocampus in response to transient forebrain ischemia. These results suggest that CCS is essential to activate SOD, and that transduction of PEP-1-CCS provides a potential strategy for therapeutic delivery in various human diseases including stroke related to SOD or ROS.