• 생명과학회지
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• 제32권4호
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• pp.318-324
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• 2022

PPARγ와 C/EBPα는 adipose tissue 발생에 필요한 핵심 adipogenic TFs이다. 두 TFs는 adipose tissue의 배아 발생에 있어 초기 adipogenesis와 adipocytes 유전자 발현을 조절한다. Adipose expansion은 adipose tissue가 태어난 뒤에도 계속 팽창이 지속되는 것을 말한다. 이러한 adipose expansion은 후기 adipogenesis의 과정인 lipogenesis가 요구된다. 특히 간과 adipose tissue은 탄수화물이 기본적으로 fatty acids으로 전환되는 de novo lipogenesis (DNL)의 주요 장기이다. Fatty acids는 이어서 glycerol-3-phosphate에 에스테르화되어 adipocytes의 lipid droplets 생성을 위해 triglycerides로 전환된다. 간의 DNL이 활발하게 연구가 된 반면, in vivo에서 adipocytes의 DNL은 아직 잘 알려져 있지 않다. 그러므로, adipose expansion과 DNL에 대한 이해는 비만, 2형 당뇨 그리고 대사성 질환을 위한 치료제 개발에 도움을 줄 수 있다. Adipocytes에서 DNL 유전자 발현은 ChREBP나 SREBP1a와 같은 lipogenic TFs 뿐 아니라, lipogenesis coactivator에 의해 전사 수준에서 조절된다. 최근 in vivo 연구에 의해 lipogenesis 유전자 발현과 adipose expansion의 새로운 측면이 밝혀졌다. 향후 구체적인 분자기전 연구는 어떻게 영양분이 DNL과 adipose expansion을 조절하는 지를 규명해 줄 것이다. 본 리뷰논문은 전사조절 관점에서 adipocytes와 adipose expansion에 있어 DNL에 대한 최신 연구결과를 요약정리 할 것이다.

• BMB Reports
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• 제32권3호
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• pp.232-238
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• 1999

Sex differences in the induction of microsomal cytochrome P-450 (CYP) and the activities of several related enzymes of Sprague-Dawley rats treated with 1-bromopropane (1-BrP) were investigated. Male and female rats were exposed to 50, 300, and 1800 ppm of 1-BrP per kg body weight (6 h a day,S days a week, 8 weeks) by inhalation. The mean body weight of 1-BrP treated groups increased according to the day elapsed, but four and five weeks respectively after the start of the exposure, the mean body weight of male and female rats had significantly reduced in the group treated with 1800 ppm 1-BrP compared with the control group (p<0.01). While the relative weights of liver increased in both sexes, statistical significance in both sexes was found only in the group receiving 1800 ppm/kg of 1-BrP (p<0.01). The total contents of CYP, $b_5$, NADPH-P-450 reductase, NADH $b_5$ reductase, ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-O-dealkylase (PROD), and p-nitrophenol hydroxylase (pNPH) activities were examined for the possible effects of 1-BrP. No significant changes in the CYP and $b_5$ contents, NADPH-P-450 reuctase, NADH $b_5$ reductase, ethoxyresorufin-O-deethylase (EROD), and pentoxyresorufin- O-dealkylase (PROD) were observed between the control and treated groups. The activity of pNPH increased steadily with the increase in the concentration of 1-BrP in both sexes, but was significantly increased only in the 1800 ppm-treated group of male rats (p<0.05). When Western blottings were carried out with three monoclonal antibodies (MAb 1-7-1, MAb 2-66-3, and MAb 1-98-1) which were specific against CYP1A1/2, CYP2B1/2, and CYP2E1, respectively, a strong signal corresponding to CYP2E1 was observed in microsomes obtained from rats treated with 1-BrP. Glutathione S-transferase (GST) activity and the content of lipid peroxide significantly increased in the treated groups compared with the control group (p<0.05). These results suggest that 1-BrP can primarily induce CYP2E1 as the major form and that GST phase II enzymes play important roles in 1-BrP metabolism, showing sex-dependence in the metabolic mechanism of 1-BrP in the rat liver.

• Journal of Plant Biotechnology
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• 제35권2호
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• pp.133-140
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• 2008

DNA와 histone 단백질의 변형은 식물 발달에 상당히 중요한 역할을 하는 것으로 알려져 있다. 식물 조직 배양 및 식물 발달 단계에서 methylation의 영향을 알아보고자 벼 종자로부터 캘러스 형성 및 식물체 재분화 단계에서 demethylation 물질인 5-azacytidine을 처리하여 유전자 발현 양상을 분석하였다. 식물체로의 재분화 능력이 있는 벼 배상체 캘러스는 5-azaC가 첨가된 H6A 배지에서는 형성되지 않았으며 갈색을 띠는 캘러스가 형성되었다. 또한 정상적인 캘러스를 5-azaC가 첨가된 MSRA 재분화 배지에서 배양했을 때도 대조구와는 달리 식물체 재분화는 이루어지지 않았다. 이러한 결과는 5-azaC가 정상적인 배상체 캘러스 및 shoot 분화에 부정적인 영향을 미친다는 것을 나타냈으며 따라서 DNA methylation이 식물 조직배양에서의 정상적인 세포 dedifferentiation과 differentiation에 필수 요인이라는 것을 알 수 있었다. 벼 캘러스 형성 및 재분화 과정 동안의 methylation 영향을 알아보고자 각 단계별로 5-azaC를 처리 후 $GeneFishig^{TM}$ DEG와 DNA chip을 사용하여 유전자 발현 양상을 분석하였다. Epigenetic regulation, 전자전달, 핵산대사, 스트레스 반응에 관여하는 일부 유전자들의 발현이 증가하거나 감소하는 것을 알 수 있었다. 발현 차이가 있는 일부 유전자를 클로닝하여 확인하였고 RT-PCR 및 northern 분석으로 각 단계에서의 발현 차이를 할인하였다.

• 동의생리병리학회지
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• 제27권6호
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• pp.802-808
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• 2013

Here we tried to uncover the potential anti-lipogenic effect and the underlying mechanism of Phaseolus angularis seed in a cellular model of nonalcoholic fatty liver disease (NAFLD) induced in HepG2 cells. Ethanol extract of Phaseolus angularis seed (JSD) was prepared. HepG2 cells were incubated in palmitate containing media to induce intracellular lipid accumulation, and co-treated with JSD for 16 hrs before examine intracellular lipid content. In control group, the cells were not co-treated with JSD. We measured the effects of JSD on liver X receptor ${\alpha}$ ($LXR{\alpha}$) and sterol regulatory element-binding transcription factor-1c (SREBP-1c) expression, transcription level of lipogenic genes, including acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and AMP-activated protein kinase (AMPK) activation in HepG2 cells. JSD markedly reduced palmitate-induced intracellular lipid accumulation in HepG2 cells. JSD suppressed $LXR{\alpha}$/SREBP-1c expression, and SREBP-1c mediated induction of ACC, FAS, and SCD-1. Furthermore, JSD activated AMPK, which plays a major role in the control of hepatic lipid metabolism. Taken together, it is suggested that JSD has a potential to alleviate hepatic steatosis, at least in part, by suppressing $LXR{\alpha}$/SREBP-1c mediated induction of lipogenic genes. In addtion, the anti-lipogenic potential may be associated with activation of AMPK. Therefore, the Phaseolus angularis seed could be applied as a potential therapeutics for NAFLD with additional clinical studies.

• Toxicological Research
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• 제27권2호
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• pp.61-70
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• 2011

Brominated flame retardants (BFRs) are present in many consumer products ranging from fabrics to plastics and electronics. Wide use of flame retardants can pose an environmental hazard, which makes it important to determine the mechanism of their toxicity. In the present study, dose-dependent toxicity of tetrabromobisphenol A (TBBPA), a flame retardant, was examined in male prepubertal rats (postnatal day 18) treated orally with TBBPA at 0, 125, 250 or 500 mg/kg for 30 days. There were no differences in body weight gain between the control and TBBPA-treated groups. However, absolute and relative liver weights were significantly increased in high dose of TBBPA-treated groups. TBBPA treatment led to significant induction of CYP2B1 and constitutive androstane receptor (CAR) expression in the liver. In addition, serum thyroxin (T4) concentration was significantly reduced in the TBBPA treated group. These results indicate that repeated exposure to TBBPA induces drug-metabolising enzymes in rats through the CAR signaling pathway. In particular, TBBPA efficiently produced reactive oxygen species (ROS) through CYP2B1 induction in rats. We measured 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage, in the kidney, liver and testes of rats following TBBPA treatment. As expected, TBBPA strongly induced the production of 8-OHdG in the testis and kidney. These observations suggest that TBBPA-induced target organ toxicity may be due to ROS produced by metabolism of TBBPA in Sprague-Dawley rats.

• The Korean Journal of Physiology and Pharmacology
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• 제19권5호
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• pp.451-460
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• 2015

Sirtuin 1 (SIRT1) is a mammalian $NAD^+$-dependent protein deacetylase that regulates cellular metabolism and inflammatory response. The organ-specific deletion of SIRT1 induces local inflammation and insulin resistance in dietary and genetic obesity. Macrophage-mediated inflammation contributes to insulin resistance and metabolic syndrome, however, the macrophage-specific SIRT1 function in the context of obesity is largely unknown. C57/BL6 wild type (WT) or myeloid-specific SIRT1 knockout (KO) mice were fed a high-fat diet (HFD) or normal diet (ND) for 12 weeks. Metabolic parameters and markers of hepatic steatosis and inflammation in liver were compared in WT and KO mice. SIRT1 deletion enhanced HFD-induced changes on body and liver weight gain, and increased glucose and insulin resistance. In liver, SIRT1 deletion increased the acetylation, and enhanced HFD-induced nuclear translocation of nuclear factor kappa B (NF-${\kappa}B$), hepatic inflammation and macrophage infiltration. HFD-fed KO mice showed severe hepatic steatosis by activating lipogenic pathway through sterol regulatory element-binding protein 1 (SREBP-1), and hepatic fibrogenesis, as indicated by induction of connective tissue growth factor (CTGF), alpha-smooth muscle actin (${\alpha}$-SMA), and collagen secretion. Myeloid-specific deletion of SIRT1 stimulates obesity-induced inflammation and increases the risk of hepatic fibrosis. Targeted induction of macrophage SIRT1 may be a good therapy for alleviating inflammation-associated metabolic syndrome.

• Reproductive and Developmental Biology
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• 제30권3호
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• pp.157-162
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• 2006

본 연구에서는 인간 부자상선 호르몬의 발현을 유도적으로 조절할 수 있는 retrocvirus vector system을 확립하고자 하였다. 이에 tetracycline계 물질로 발현을 유도적으로 조절할 수 있는 one vector 형태의 Tet-On system을 이용하였으며 WPRE 서열을 도입하여 유도적 조건에서 외래 유전자의 발현을 증가시켰다. 구축한 각각의 표적세포에서 RT-PCR과 ELISA를 이용하여 hPTH유전자의 발현 정도를 비교 측정한 결과, WPRE가 hPTH의 3' 위치에 도입된 $RevTRE-PTH-WPRE-CMVp-rtTA2^sM2$ virus를 이용하여 유전자를 전이시킨 경우에 hPTH의 발현량이 가장 높은 것으로 나타났고, 또한 유도율도 가장 큰 것으로 확인되었다. 이 system을 이용하여 생산한 고감염가의 virus는 인간의 부갑상선 호르몬을 생산하기 위한 동물세포주의 구축이나 형질전환 동물의 생산에 있어서 매우 효율적인 유전자 전이 수단이 될 것으로 사료된다.

• Journal of Chest Surgery
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• 제34권6호
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• pp.465-471
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• 2001

배경: 저체온은 뇌 대사를 억제하여 뇌를 보호한다고 알려져 있으며, 대동맥 질환 수술 시 완전 순환 정지전에 충분히 시행되고 있다. 일반적으로 임상에서 직장 또는 비인두 온도를 지표로 순환정지를 시행하고 있으나, 순환정지 시 적절한 저체온의 온도 범위나 순환정지 온도를 결정하는 객관적인 지표에 대해서는 아직 명확한 결론이 없다. 본 연구는 수술 중 뇌파검사를 이용해 완전 순환 정지 시 안전한 직장 및 비인두 온도의 적정 수준을 확인하고, 적절한 저체온의 지표로서 뇌파검사의 역할을 알아보고자 하였다. 대상 및 방법: 1999년 3월부터 2000년 8월 31일까지 대동맥 질환으로 대동맥 인조혈관 치환수술 동안 뇌파검사를 병행하면서 완전 순환 정지를 했던 27명의 환자를 대상으로 하였다. 직장 온도와 비인두 온도를 마취유도부터 계속 감시하였으며, 뇌파검사는 10개의 채널로 마취유도부터 뇌 전위 고요상태(electrocerebral silence) 가지 관찰하였다 결과: 뇌 전위 고요 상태에 도달했을 때의 직장 온도와 비인두 온도는 일정한 범위에 있지 않고 다양한 값(직장 11$^{\circ}C$~$25^{\circ}C$; 비인두 7.7$^{\circ}C$ ~23$^{\circ}C$)을 보였으며, 두 온도 사이에 서로 관련이 없었다(p=0.171). 체외순환을 시작하여 뇌 전위 고요상태에 이르기까지 냉각 시간은 25~127분으로 다양하였으며, 환자의 체표면적과 연관이 있었다(p=0.027). 결과: 뇌 전위 고요상태는 다양한 체온에서 발생했으며, 임상에서 일반적으로 적용되는 직장 및 비인두 온도는 뇌 전위 고요상태를 지적할 수 없었다. 그러므로 심혈관계 수술 시 체온에 근거한 저체온 완전 순환 정지는 뇌의 보호를 확신할 수 없으며, 수술 중 뇌파검사의 관찰은 안전한 순환정지를 위한 적절한 저체온의 수준을 확보하기 위해 필요하며 합리적인 방법이었다.

• Nutritional Sciences
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• 제6권3호
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• pp.148-154
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• 2003

Although various raw plant materials have been demonstrated to exert anti-obesity effects to a greater or lesser extent in both humans and animals when they are used to supplement the diet, it has not been shown extensively that they influence adipocyte cell differentiation involving lipid metabolic gene expressions. Using a well-established 3T3-L1 preadipocyte differentiation system, we decided to look into molecular and cellular event occurring during adipocyte differentiation when raw plant materials aye included in the process, in an effort to demonstrate the potential use of a screening system to define the functions of traditionally well-known materials. To these ends, the effects of ethanol (EtOH) or EtOH/distilled water (DW) extracts of Wax Gourd were examined using cytochemical and molecular analyses to determine whether components of the extracts modulate adipocyte differentiation of 3T3-Ll preadipocytes in vitro. The cytochemical results demonstrated that EtOH or EtOH/DW extracts did not affect lipid accumulation and cell proliferation, although the degree of lipid accumulation was influenced slightly depending on the extract. EtOH extract was highly effective in apoptotic induction during differentiation of 3T3-Ll preadipocytes (p<0.05). Reverse transcription-polymerase chain reaction (RT-PCR) analysis of lipoprotein lipase (LPL), Uncoupling protein (Ucp) 2, 3 and 4 also showed that while LPL expression was not influenced, Ucp2, 3 and 4 were up regulated in the EtOH extract-treated group and down regulated in the EtOH/DW extract-treated group. These changes in gene expressions suggest that the components in different fractions of Wax Gourd extracts may modulate lipid metabolism by either direct or indirect action. Taking these results together, it was concluded that molecular and cellular analyses of adipocyte differentiation involving lipid metabolic genes should facilitate understanding of cellular events occurring during adipocyte differentiation. Furthermore, the experimental scheme and analytical methods used in this study should provide a screening system for the functional study of raw plant materials in obesity research.

• 한국산업보건학회지
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• 제19권1호
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• pp.30-38
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• 2009

The objective of this study was to evaluate the effects of occupational exposure to styrene on the components of metabolic syndrome. We surveyed 263 employees, among whom 117workers we ere chronically exposed to styrene in glass-reinforced plastic boat manufacturing factories and 146 controls had never been occupationally exposed to styrene as will as hazardous chemicals. The general and job characteristics such as age, smoking and drinking habit, working hours and duration were not significant different except sleeping hours(p<0.05). Among the components of metabolic syndrome, the systolic blood pressure, total cholesterol, HDL-cholesterol and fasting glucose were significantly higher in exposed workers. On multiple logistic regression analysis for the components of metabolic syndrome, waist circumference was insulin (OR=1.129), blood pressure was MA(OR=14.724), fasting glucose(OR=1.191) and metabolic syndrome(OR=1.110) were significantly associated with insulin. The mean concentration of airborne styrene was $ 38.1{\pm}40.1$ ppm, blood concentrations of glucose and insulin and levels of HOMA-IR in over 50 ppm exposed group were higher than in blow 50 ppm exposed group. These results suggested that the exposure of styrene affects blood pressure, fasting glucose and insulin levels and that dysfunction and/or declination in glucose and insulin metabolism might induced ultimately insulin resistance and metabolic syndrome.