• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2002년도 창립10주년기념 및 국립독성연구원 의약품동등성평가부서 신설기념 국재학술대회:생물학적 동등성과 의약품 개발 전략을 위한 국제심포지움
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• pp.113-113
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• 2002

Phylogenetically conserved Bcl-2 family proteins play a pivotal role in the regulation of apoptosis from virus to human. Members of the Bcl-2 family consist of antiapoptotic proteins such as Bcl-2, Bcl-xL, and Bcl-w, and proapoptotic proteins such as BAD, Bax, BOD, and Bok. It has been proposed that anti- and proapoptotic Bcl-2 proteins regulate cell death by binding to each other and forming heterodimers. A delicate balance between anti- and proapoptotic Bcl-2 family members exists in each cell and the relative concentration of these two groups of proteins determines whether the cell survives or undergoes apoptosis. Mcl-1 (Myeloid cell :leukemia-1) is a member of the Bcl-2 family proteins and was originally cloned as a differentiation-induced early gene that was activated in the human myeloblastic leukemia cell line, ML-1 . Mcl-1 is expressed in a wide variety of tissues and cells including neoplastic ones. We recently identified a short splicing variant of Mcl-1 short (Mcl-IS) and designated the known Mcl-1 as Mcl-1 long (Mcl-lL). Mcl-lL protein exhibits antiapoptotic activity and possesses the BH (Bcl-2 homology) 1, BH2, BH3, and transmembrane (TM) domains found in related Bcl-2 proteins. In contrast, Mcl-1 S is a BH3 domain-only proapoptotic protein that heterodimerizes with Mcl-lL. Although both Mc1-lL and Mcl-lS proteins contain BH domains fecund in other Bcl-2 family proteins, they are distinguished by their unusually long N-terminal sequences containing PEST (proline, glutamic acid, serine, and threonine) motifs, four pairs of arginine residues, and alanine- and glycine-rich regions. In addition, the expression pattern of Mcl-1 protein is different from that of Bcl-2 suggesting a unique role (or Mcl-1 in apoptosis regulation. Tankyrasel (TRF1-interacting, ankyrin-related ADP-related polymerasel) was originally isolated based on its binding to TRF 1 (telomeric repeat binding factor-1) and contains the sterile alpha motif (SAM) module, 24 ankyrin (ANK) repeats, and the catalytic domain of poly(adenosine diphosphate-ribose) polymerase (PARP). Previous studies showed that tankyrasel promotes telomere elongation in human cells presumably by inhibiting TRFI though its poly(ADP-ribosyl)action by tankyrasel . In addition, tankyrasel poly(ADP-ribosyl)ates Insulin-responsive amino peptidase (IRAP), a resident protein of GLUT4 vesicles, and insulin stimulates the PARP activity of tankyrase1 through its phosphorylation by mitogen-activated protein kinase (MAPK). ADP-ribosylation is a posttranslational modification that usually results in a loss of protein activity presumably by enhancing protein turnover. However, little information is available regarding the physiological function(s) of tankyrase1 other than as a PARP enzyme. In the present study, we found tankyrasel as a specific-binding protein of Mcl-1 Overexpression of tankyrasel led to the inhibition of both the apoptotic activity of Mel-lS and the survival action of Mcl-lL in mammalian cells. Unlike other known tankyrasel-interacting proteins, tankyrasel did not poly(ADP-ribosyl)ate either of the Mcl-1 proteins despite its ability to decrease Mcl-1 proteins expression following coexpression. Therefore, this study provides a novel mechanism to regulate Mcl-1-modulated apoptosis in which tankyrasel downregulates the expression of Mcl-1 proteins without the involvement of its ADP-ribosylation activity.

• Molecular & Cellular Toxicology
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• 제4권4호
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• pp.348-354
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• 2008

Bisphenol A (BPA), an environmental endocrine disrupter, enters the human body continuously in food and drink. Young children are likely to be more vulnerable than adults to chemical exposure due to the immaturities of their organ systems, rapid physical development, and higher ventilation, metabolic rates, and activity levels. The direct effect of BPA on peripheral tissue might also be of importance to the development of insulin resistance. However, the influence that BPA has on insulin signaling molecules in skeletal muscle has not been previously investigated. In this study, we examined the effect of BPA on fasting blood glucose (FBG) in post-weaned Wistar rats and on insulin signaling proteins in C2C12 skeletal muscle cells. Subsequently, we investigated the effects of BPA on insulin-mediated Akt phosphorylation in C2C12 myotubes. In rats, BPA treatment (0.1-1,000 ng/mL for 24 hours) resulted in the increase of FBG and plasma insulin levels, and reduced insulin-mediated Akt phosphorylation. Furthermore, the mRNA expression of insulin receptor (IR) was decreased after 24 hours of BPA treatment in C2C12 cells in a dose-dependent manner, whereas the mRNA levels of other insulin signaling proteins, including insulin receptor substrate-1 (IRS-1) and 5'-AMP-dependent protein kinase (AMPK), were unaffected. Treatment with BPA increased GLUT4 expression and protein tyrosine phosphatase 1B (PTP1B) activity in C2C12 myotubes, but not in protein levels. We conclude that exposure to BPA can induce insulin resistance by decreasing IR gene expression, which is followed by a decrease in insulin- mediated Akt activation and increased PTP1B activity.

• Current Research on Agriculture and Life Sciences
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• 제20권
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• pp.55-63
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• 2002

세리신 잠의 발육, 실샘 성장, 세리신 량, 혈액 아미노산 조성 등 세리신 잠의 특성을 알아보기 위하여 잠 120 과 같은 조건으로 사육하여 얻은 결과는 다음과 같다. 1. 부화율에 있어서 세리신 잠은 85%이며 잠 120 은 95%이었다. 특히 세리신 잠은 부화가 고르지 않았다. 2. 유충 기간에 있어서 세리신은 20 일 23 시간이었고, 잠 120 은 21 일 22시간이었다. 3. 실샘에 있어서 세리신 잠은 중부실샘이 대부분이며 후부 실샘의 길이는 약 2~3cm 이었고 굴곡은 없었다. 4. 세리신 잠에 있어서 상족후 나방까지의 기간은 약 12 일이었으며, 화용후 화아까지는 7 일로 대단히 짧은 특성을 보였다. 5. 고치에 있어서 세리신 잠은 이주 얇고 가벼웠으며 견충중은 2.7cg 이며 견충 비율은 3.65%이였다. 6. 세리신 (sericin protein)양에 있어서, 세리신 잠의 견충이 sericin 만 으로 구성되어 있고 잠 120 은 28%가 sericin 이었다. 세리신 잠의 견충 당 sericin 율은 잠 120 의 34.6%정도였다. 7. 혈액 아미노산의 양에 있어서 세리신 잠은 histidine, lysine, glutamic acid 가 많았으며 5 령 발육에 따른 조성의 변화에 있어서 대부분의 혈액 아미노산들은 증가하였다.

• 한국항만경제학회:학술대회논문집
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• 한국항만경제학회 2006년도 국제학술대회
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• pp.1-12
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• 2006

As national economies globalize, demand for intercontinental container shipping services is growing rapidly, providing a potential economic boon for the countries and communities that provide port services. On the promise of profits, many governments are investing heavily in port infrastructure, leading to a possible glut in port capacity, driving down prices for port services and eliminating profits as ports compete for business. Further, existing ports are making strategic investments to protect their market share, increasing the chance new ports will be overcapitalized and unprofitable. Governments and port researchers need a tool for understanding how local competition in their region will affect demand for port services at their location, and thus better assess the profitability of a prospective port. We propose to develop such a tool by extending our existing simulation model of global container traffic to incorporate demand-side shipper preferences and supply-side strategic responses by incumbent ports to changes in the global port network, including building new ports, scaling up existing ports, and unexpected port closures. We will estimate shipper preferences over routes, port attributes and port services based on US and international shipping data, and redesign the simulation model to maximize the shipper's revealed preference functions rather than simply minimize costs. As demand shifts, competing ports will adjust their pricing (short term) and infrastructure (long term) to remain competitive or defend market share, a reaction we will capture with a game theoretic model of local monopoly that will predict changes in port characteristics. The model's hypotheses will be tested in a controlled laboratory experiment tailored to local port competition in Asia, which will also serve to demonstrate the subtle game theoretic concepts of imperfect competition to a policy and industry audience. We will apply the simulation model to analyze changes in global container traffic in three scenarios: addition of a new large port in the US, extended closure of an existing large port in the US, and cooperative and competitive port infrastructure development among Korean partner countries in Asia.

• Journal of Nutrition and Health
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• 제54권6호
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• pp.594-602
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• 2021

본 연구는 고지방식이로 유도한 비만 동물모델에서 아연의 식이를 통한 보충 급여가 혈당 조절과 골격 근육의 ZIP7의 작용에 미치는 영향에 대해 살펴보았다. 고지방식이를 공급한 HF군은 정상 대조군에 비하여 단위 체중당 골격 근육 무게가 유의하게 감소하였으며, 혈당은 유의적으로 증가하였다. 고지방식이와 함께 아연을 보충 공급한 HF+Zn군은 아연을 보충하지 않은 HF군과 비교하여, 공복 혈당과 경구 포도당 부하 후 혈당 증가 면적이 유의하게 감소하였다. 또한, HF+Zn군은 HF군에 비해 골격 근육의 ZIP7 단백질 수준이 유의하게 증가하였으며, AKT 활성과 GLUT4 단백질 수준도 유의하게 증가하는 것으로 나타났다. 이상의 결과를 종합해 볼 때, 아연 보충은 비만으로 인한 고혈당 증세를 완화하는 효과를 나타내며, 이는 골격 근육에서의 ZIP7 아연 수송체에 의한 당 대사 조절과 관련이 있을 것으로 생각된다.

• Animal Bioscience
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• 제35권1호
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• pp.64-74
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• 2022

Objective: This study was conducted to investigate the effects of dietary multi-strain probiotic (MSP) (Bacillus coagulans Unique IS2 + Bacillus subtillis UBBS14 + Saccharomyces boulardii Unique 28) on performance, gut morphology and expression of nutrient transporter related genes in broiler chickens. Methods: A total of 256 (4×8×8) day-old CARIBRO Vishal commercial broiler chicks of uniform body weight were randomly distributed into four treatments with 8 replicates each and having eight chicks in each replicate. Four dietary treatments were T₁ (negative control-basal diet), T₂ (positive control-antibiotic bacitracin methylene disalicylate at 20 mg/kg diet), T₃ (MSP at 10⁷ colony-forming unit [CFU]/g feed), and T₄ (MSP at 10⁸ CFU/g feed). Results: During 3 to 6 weeks and 0 to 6 weeks, the body weight gain increased significantly (p<0.05) in T₃ and T₄ groups. The feed intake significantly (p<0.05) reduced from T₁ to T₃ during 0 to 3 weeks and the feed conversion ratio also significantly (p<0.05) improved in T₃ and T₄ during 0 to 6 weeks. The humoral and cell mediated immune response and the weight of immune organs were also significantly (p<0.05) improved in T₃ and T₄. However, significant (p<0.05) dietary effects were observed on intestinal histo-morphometry of ileum in T₃ followed by T₄ and T₂. At 14 d post hatch, the relative gene expression of glucose transporter (GLUT5), sodium-dependent glucose transporter (SGLT₁) and peptide transporter (PepT₁) showed a significant (p<0.05) up-regulating pattern in T₂, T₃, and T₄. Whereas, at 21 d post hatch, the gene expression of SGLT₁ and PepT₁ was significantly (p<0.05) downregulated in MSP supplemented treatments T₃ and T₄. Conclusion: The supplementation of MSP at 10⁷ CFU/g diet showed significant effects with improved performance, immune response, gut morphology and expression of nutrient transporter genes. Thus, the MSP could be a suitable alternative to antibiotic growth promoters in chicken diets.

• 한방비만학회지
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• 제22권2호
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• pp.93-101
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• 2022

Objectives: This study aimed to observe the anti-diabetic effect and underlying mechanisms of Galgunhwanggumhwangryun-tang (GHH; Gegen-Qinlian-decoction) in the C2C12 myotubes. Methods: GHH (1.0 mg/ml) or metformin (0.75 mM) or insulin (100 nM) were treated in C2C12 myotubes after 4 days differentiation. The glucose uptake was assessed by 2-[N-(7-160 nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose uptake by C2C12 cells. The expression of adenosine monophosphate-activated protein kinase (AMPK) and phosphorylation AMPK (pAMPK) were measured by western blot. We also evaluated gene expression of glucose transporter type 4 (Slc2a4, formerly known as GLUT4), glucokinase (Gk), carnitine palmitoyltransferase IA (Cpt1a), nuclear respiratory factors 1 (Nrf1), mitochondrial transcription factor A (Tfam), and peroxisome proliferator-activated receptor γ coactivator 1α (Ppargc1a) by quantitative real-time polymerase chain reaction. Results: GHH promoted glucose uptake in C2C12 myotubes. The expression of AMPK protein, which plays an essential role in glucose metabolism, was increased by treatment with GHH. GHH treatment tended to increase gene expression of Slc2a4, Gk, and Nrf1 but was not statistically significant. However, GHH significantly improved Tfam and Ppargc1a gene expression in C2C12 myotubes. Conclusions: In summary, GHH treatment promoted glucose uptake in C2C12 myotubes. We suggest that these effects are associated with increased gene expression involved in mitochondrial biosynthesis and oxidative phosphorylation, such as Tfam and Ppargc1a, and increased expression of AMPK protein.

• 운동영양학회지
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• 제16권2호
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• pp.65-71
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• 2012

Oxygen is the final acceptor of electron transport from fat and carbohydrate oxidation, which is the rate-limiting factor for cellular ATP production. Under altitude hypoxia condition, energy reliance on anaerobic glycolysis increases to compensate for the shortfall caused by reduced fatty acid oxidation [1]. Therefore, training at altitude is expected to strongly influence the human metabolic system, and has the potential to be designed as a non-pharmacological or recreational intervention regimen for correcting diabetes or related metabolic problems. However, most people cannot accommodate high altitude exposure above 4500 M due to acute mountain sickness (AMS) and insulin resistance corresponding to a increased levels of the stress hormones cortisol and catecholamine [2]. Thus, less stringent conditions were evaluated to determine whether glucose tolerance and insulin sensitivity could be improved by moderate altitude exposure (below 4000 M). In 2003, we and another group in Austria reported that short-term moderate altitude exposure plus endurance-related physical activity significantly improves glucose tolerance (not fasting glucose) in humans [3,4], which is associated with the improvement in the whole-body insulin sensitivity [5]. With daily hiking at an altitude of approximately 4000 M, glucose tolerance can still be improved but fasting glucose was slightly elevated. Individuals vary widely in their response to altitude challenge. In particular, the improvement in glucose tolerance and insulin sensitivity by prolonged altitude hiking activity is not apparent in those individuals with low baseline DHEA-S concentration [6]. In addition, hematopoietic adaptation against altitude hypoxia can also be impaired in individuals with low DHEA-S. In short-lived mammals like rodents, the DHEA-S level is barely detectable since their adrenal cortex does not appear to produce this steroid [7]. In this model, exercise training recovery under prolonged hypoxia exposure (14-15% oxygen, 8 h per day for 6 weeks) can still improve insulin sensitivity, secondary to an effective suppression of adiposity [8]. Genetically obese rats exhibit hyperinsulinemia (sign of insulin resistance) with up-regulated baseline levels of AMP-activated protein kinase and AS160 phosphorylation in skeletal muscle compared to lean rats. After prolonged hypoxia training, this abnormality can be reversed concomitant with an approximately 50% increase in GLUT4 protein expression. Additionally, prolonged moderate hypoxia training results in decreased diffusion distance of muscle fiber (reduced cross-sectional area) without affecting muscle weight. In humans, moderate hypoxia increases postprandial blood distribution towards skeletal muscle during a training recovery. This physiological response plays a role in the redistribution of fuel storage among important energy storage sites and may explain its potent effect on changing body composition. Conclusion: Prolonged moderate altitude hypoxia (rangingfrom 1700 to 2400 M), but not acute high attitude hypoxia (above 4000 M), can effectively improve insulin sensitivity and glucose tolerance for humans and antagonizes the obese phenotype in animals with a genetic defect. In humans, the magnitude of the improvementvaries widely and correlates with baseline plasma DHEA-S levels. Compared to training at sea-level, training at altitude effectively decreases fat mass in parallel with increased muscle mass. This change may be associated with increased perfusion of insulin and fuel towards skeletal muscle that favors muscle competing postprandial fuel in circulation against adipose tissues.

• Journal of Nutrition and Health
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• 제48권4호
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• pp.299-309
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• 2015

기존 연구에서 주로 사용하는 기타 재래종 검정콩 종피추출물 (콩단백질 혹은 총 안토시안)의 효과를 연구하는 경우와 달리, 본 연구에서는 재래종 서리태보다 C3G와 D3G 안토시안이 2배 이상 풍부한 검정콩 CJ-3호 종피추출물을 이용하였다. STZ로 유도된 당뇨쥐에 4주간 검정콩 CJ-3호 종피추출물을 처치한 결과 비록 체중감소, 혈당강하, 인슐린저항성 완화 등의 효과는 미비하지만 근육량이 유의적으로 증가하였는데 이는 일반적으로 항비만 식이요법에 따라 나타나는 근육소모를 보완하는 중요한 효과이다. STZ유도 당뇨 쥐에서 억제된 글리코겐이용률이 검정콩 CJ-3호 종피추출물에 의하여 증가한 것은 포도당이 에너지원으로 사용되면서 지방조직의 지질이용률을 억제하여 혈중 TG를 개선시켰고 간에서 HMG-CoA reductase 활성을 조절함으로써 혈청 TC를 낮추는데 기여하였다. 4주간의 투여기간을 연장한다면 향후 당뇨에서 발생하는 인슐린저항성 및 당화적 산화성억제에 따른 지질의 과산화물의 생성을 억제할 수 있는 가능성도 기대할 수 있겠다. 또한 검정콩 CJ-3호는 병 저항성이 높고 종실특성이 우수한 녹자엽 검정콩으로 생산성이 높아서 기능성에 대한 반복 실험을 확인한다면 기능성식품시장의 산업화도 가능하다. 따라서 C3G와 D3G 안토시안이 풍부한 기능성 식품의 경우 당뇨, 비만 및 암 등 난치병질환에서 나타나는 혈중지질 개선을 위한 임상적 효과 또한 기대해 볼 수 있겠다.

• 대한핵의학회지
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• 제38권2호
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• pp.180-189
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• 2004

다약제내성이 발현된 암세포에서 세포내의 항암제를 세포외로 배출시키는 기전을 체내에서 비침습적인 방법으로 영상화 할 수 있는 SPECT와 PET는 악성종양의 진단과 평가에 중요한 역할을 할 것으로 판단되나, 아직까지도 Pgp와 MRP의 운반능을 적절하게 평가하는 핵의학적 영상방법을 정립하는데는 극복해야할 문제점들이 많다. 지금까지의 MDR영상에 관한 연구들은 대부분이 $^{99m}Tc$-표지 방사성의약품을 이용한 연구였으나, PET의 임상 응용이 증가함에 따라 보다 특이적이고 쉽게 응용될 수 있는 PET용 방사성 추적자의 개발도 이루어져야 할 것이다. $^{99m}Tc$-MIBI의 암 세포내 일방향(unidirectional) 섭취는 음성인 세포막 전하와 세포내 소립체 기질 전하에 의하여 결정되므로, MIBI의 섭취는 다른 지용성 양전하를 띤 막전위 추적자들과 유사하게 작용한다. $^{99m}Tc$-표지 방사성의약품은 암조직의 혈류 증가나 소립체 용적이나 활성도가 증가하면 섭취가 증가할 수 있어 보다 특이적인 MDR추적제의 개발이 필요한 것이다. 최근 Lorke 등은 약제감수성 및 내성 인체대장암세포인 $HT-29^{par}$ 세포와 $HT-29^{mdrl}$ 세포를 이용한 연구에서, 두세포 모두에서 $^{18}F$-FDG의 섭취가 있었고, MDR이 발현된 세포와 종양에서 $^{18}F$-FDG 섭취가 훨씬 낮았고, MIBI는 MDR이 없는 모세포에서도 매우 낮았음을 보고한 바 있다. 이 세포는 전자현미경검사에서 사립체가 풍부하지 않은 세포였다. 그러므로 이러한 결과로 보아 $^{99m}Tc$-MIBI 영상에서 종양이 보이지 않거나 섭취가 미약하다고 해도 MDR이 발현되었다고 단정할 수는 없게 된다. 즉 MDR의 발현유무를 정확하게 감별할 수 있기 위하여는 저항이 없는 세포에 MIBI가 충분하게 섭취되어야 한다는 것이 필수적인 요건이며, 종양세포 종류에 따라서는 FDG가 MDR의 marker가 될 수 있다는 것이다. Pgp 수송체는 ATP의존성 약제배출 펌프이므로 MDR세포는 에너지가 많이 필요하여, MDR 세포는 당분해율(rate of glycolysis)이 증가되어 있고 HT-29 mdrl 종양세포에서는 포도당 이동과정의 변화로 FDG 섭취가 감소되었다. 또한 Pgp가 점차 증가됨과 함께 plasma membrane transporter인 GLUT-1 level이 감소된다. 이러한 결과는 다약제내성의 영상화가 지금까지의 예상보다 보다 복합적이고 다양하므로 보다 많은 연구가 필요할 것이라는 점을 시사한다. 최근 시도되고 있는 생체광학 영상을 이용한 다약제내성 유전자 및 Pgp 발현 연구는 아직 시작단계이나, 분자 생물학적 영상법의 발전과 함께 MRI 기술등에도 이용될 수 있으므로 향후 많은 연구가 있을 것으로 기대된다.