DHEA의 항비만 효능 및 ob 유전자 (leptin)의 발현에 미치는 영향

정기경,신미희,한형미,강석연,김태균,강주혜,문애리,김승희 德成女子大學校 藥學硏究所 2000 藥學論文誌 Vol.11 No.1

Leptin, the product of the ob gene, is a small peptide molecule synthesized by white adipocytes with an important role in the regulation of body fat and food intake. Baesd on the evidence that synthesis of leptin is regulated by female sex hormone, estrogen, this present study was investigated whether sex hormone precursor, DHEA, can regulate obese gene expression in lean and genetically obese (ob/ob) mice. Antiobesity activity of DHEA was evaluated by determining body weight, food consumption, epididymal fat weight and serum levels of cholesterol and triglyceride in ICR, C57BL/6J, and ob/ob mice. The treatment of C57BL/6J lean and obese mice with a diet containing 0.3% and 0.6% DHEA resulted in lowered rates of weight gain in comparison to non-treated mice, although much greater response was found in the obese mice. All other concentrations of DHEA (0.015%, 0.06%, 0.15%, 0.3%) except the highest one(0.6%) showed no significant effects on weight gain in ICR mice. Food consumption was significantly decreased in all mice treated with 0.6% DHEA, whereas it was not decreased in ICR mice at lower concentrations than 0.6% DHEA. DHEA decreased significantly epididymal adipose tissue weight and serum triglyceride levels dose dependently in lean and obese mice. However, serum cholesterol levels were decreased at lower concentrations than 0.15% DHEA and increased at concentrations of 0.3% and 0.6% DHEA in lean and obese mice. These increases in serum cholestrol levels at high concentrations of DHEA might result from the fact that DHEA has a cholesterol moiety, thereby interfered the assay system. As an approach to elucidate the mechanism for antiobesity activity of DHEA, we examined mRNA levels of obese gene in the adipocyte and obese gene product (leptin) in the serum. The results showed that DHEA did not affect obese gene expression in ICR and C57BL/6J mice. Therefore, we concluded that antiobesity activity of DHEA was not modulated by obese gene expression.

작약감초탕이 미성숙 흰쥐에서 난포성숙 및 Estrogen생성에 미치는 효과

정기경,강석연,김태균,김창옥,문애리,유경자,이송득,류항묵,김승희,Jung, Ki-Kyung,Kang, Seog-Youn,Kim, Tae-Gyun,Kim, Chang-Ok,Moon, A-Ree,Ryu, Kyung-Za,Lee, Song-Deuk,Ryeu, Hang-Mook,Kim, Seung-Hee 한국생약학회 1997 생약학회지 Vol.28 No.3

The traditional herbal medicine, Jackyakgamcho-tang(JGT), was reported to decrease serum testosterone levels and make pregnancy possibel in anovulatory woman and rat. JGT contains Paeoniae Radix(PR) and Glycyrrhizae Radix(GR) in equal amount. This study was designed to investigate the effect of JGT and its components(PR, GR, paeoniflorin and glycyrrhizin) on uterine and ovarian responses, follicular development, and estrogen secretion in the immature rat. The samples(water extracts of JGT, PR, GR; pure compound of paeoniflorin and glycyrrhizin) were administered orally to rats from the 21th day of age to the 28th or 30th days of age for 7 or 9 days. JGT(400mg/kg) and PR(100mg/kg, 200mg/kg) treatments significantly increased serum estradiol above levels in control rats, but both GR and glycyrrhizin had no effect on this parameter. Gross observation and histological analysis revealed that an increased number of growing follicules was observed in the ovaries of JGT and PR treated rat. However the lutenized follicles and ova present in the oviducts were not observed in all rats except one treated with estrogen as a positive control. These results indicate that JGT stimulates the estrogen production and follicular maturation in the immature rat and PR is the main component to induce such reaction.

식품 의약품 중 유해물질의 위해 분석 연구 전망

정기경 한국환경독성학회 2011 한국독성학회 심포지움 및 학술발표회 Vol.2011 No.10

마우스세포주 Balb/c 3T3 A31-1-1에서 Epigallocatechin gallate(EGCG)의 세포암화 억제효과에 대한 유전자발현 해석

정기경,서수경,김태균,박문숙,이우선,박순희,김승희,정해관,Jung, Ki-Kyung,Suh, Soo-Kyung,Kim, Tae-Gyun,Park, Moon-Suk,Lee, Woo-Sun,Park, Sue-Nie,Kim, Seung-Hee,Jung, Hai-Kwan 한국환경성돌연변이발암원학회 2006 한국환경성돌연변이·발암원학회지 Vol.26 No.4

Previous studies showed that epigallocatechin gallate(EGCG) have substantial effects of suppressing the N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)-initiated cell transformation process on the bases of foci formation frequency and loss of anchorage dependency. In this study we tried to clarify the molecular mechanism of suppressing the cell transformation process. Mouse cell line balb/c 3T3 A31-1-1 was exposed 2 days to MNNG followed by 15 days 12-O-tetradecanoylphorbol-13-acetate(TPA) treatment for our transformation process. EGCG was added after the time point of 24 hours exposure to TPA and incubated for 19 days. 2029 genes were selected in our transformation process that showed fold change value of 1.5 or more in the microarray gene expression analysis covering the mouse full genome. These genes were found to be involved mainly in the cell cycle pathway, focal adhesion, adherens junction, TGE-$\beta$ signaling, apoptosis, lysine degradation, insulin signaling, ECM-receptor interaction. Among the genes, we focused on the 631 genes(FC>0.5) reciprocally affected by EGCG treatment. Our study suggest that EGCG down-regulate the gene expressions of up stream signaling factors such as nemo like kinase with MAPK activity and PI3-Kinase, Ras GTPase and down stream factors such as cyclin D1, D2, H, T2, cdk6.

DHEA의 항비만 효능 및 ob 유전자(leptin)의 발현에 미치는 영향

정기경,신미희,한형미,강석연,김태균,강주혜,문애리,김승희 대한약학회 2000 약학회지 Vol.44 No.5

Leptin, the product of the ob gene, is a small peptide molecule synthesized by white adipocytes with an important role in the regulation of body fat and food intake. Based on the evidence that synthesis of leptin is regulated by female sex hormone, estrogen, this present study was investigated whether sex hormone precursor DHEA, can regulate obese gene expression in lean and genetically obese (ob/ob) mice. Antiobesity activity of DHEA was evaluated by determining body weight, food consumption, epididymal fat weight and serum levels of cholesterol and triglyceride in ICR, C57BL/6J, and ob/ob mice. The treatment of C57BL/6J lean and obese mice with a diet containing 0.3% and 0.6% DHEA resulted in lowered rates of weight gain in comparison to non-treated mice, although much greater response was found in the obese mice. All other concentrations of DHEA (0.015%, 0.06%, 0.15%, 0.3%) except the highest one(0.6%) showed no significant effects on weight gain in ICR mice. Food consumption was significantly decreased in all mice treated with 0.6% DHEA, whereas it was not decreased in ICR mice at lower concentrations than 0.6% DHEA. DHEA decreased significantly epididymal adipose tissue weight and serum triglyceride levels dose dependently in lean and obese mice. However serum cholesterol levels were decreased at lower concentrations than 0.15% DHEA and increased at concentrations of 0.3% and 0.6% DHEA in lean and obese mice. These increases in serum cholestrol levels at high concentrations of DHEA might result from the fact that DHEA has a cholesterol moiety thereby interfered the assay system. As an approach to elucidate the mechanism for antiobesity activity of DHEA, we examined mRNA levels of obese gene in the adipocyte and obese gene product (leptin) in the serum. The results showed that DHEA did not affect obese gene expression in ICR and C57BL/6J mice. Therefore, we concluded that antiobesity activity of DHEA was not modulated by obese gene expression.

Poster Ⅰ : PART A : Proteins - Structure , Functions & Modifications ; Purification and Characterization of Protein Methylase Ⅱ from Porcine Testis

정기경,홍성렬 한국생화학분자생물학회 (구 한국생화학회) 1991 추계학술대회집 Vol.- No.-

Curcumin이 microglia의 활성화에 미치는 영향

정기경(Ki Kyung Jung),이상진(Sang Jin Lee),이선우(Sun Woo Yi),강석연(Seog Young Kang),김태균(Tae Gyun Kim),강주혜(Ju Hye Kang),홍성렬(Sung Youl Hong),주일로(Ilo Jou),김승희(Seung Hee Kim),한형미(Hyung Mee Han) 대한약학회 2000 약학회지 Vol.44 No.5

Microglia, brain resident macrophages, play a central role in the inflammatory responses of the brain and are activated in brain injuries and several neurodegenerative diseases such as Alzheimer's and Parkinson's disease, thereby aggravating the course of these diseases. In this study, the effects of plant-derived compounds such as curcumin or gingerol on the microglial activation were examined. Microglial cultures were prepared from 2-3 week mixed primary glial cultures obtained from the cerebral cortex of 1-2 day old rats and identified by immunocytochemistry using microglial-specific antibody OX-42. Microglia were activated by lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) and the effect of curcumin or 6-gingerol on the microglial activation was examined. Specific parameters measured to monitor microglial activation were nitric oxide (NO), prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF-alpha) release. Curcumin (1-10mcM) inhibited NO release induced by LPS and IFN-gamma in a dose-dependent manner whereas 6-gingerol (2-20mcM) did not have any effect on LPS/IFN-gamma-induced NO release. The levels of PGE2 and TNF-alpha induced by LPS and IFN-gamma were also inhibited by 1-10pM curcumin in a dose-dependent manner. These results showed that curcumin could modulate microglial activation.

Effects of Curcumin on the Modulation of Microglial Activation(Ⅱ)

Jung, ki Kyung,Lee, Jin Ho,Han, Hyung Mee,Kim, Tae Gyun,Kang, Ju Hye,Jou, Ilo,Hong, Sungyoul,Kim, Seung Hee,Kang, Seog Youn 식품의약품안전청 2000 식품의약품안전청 연보 Vol.4 No.-

뇌손상 및 Alzheiirler's disease등 만성 염증을 동반하는 뇌질환을 악화시키는 원인이 된다고 알려진 microglia의 활성화를 카레의 주성분인 curcumin이 억제하는지 알아보고자 하였다. 쟁후 0일에서 2일된 rat의 대뇌피질로부터 rrlicroglial cell을 2~3주간 배양하여 얻은 다음 LPS와 fFN-r로 활성화를 유도하고 curcumin을 I~SrM 범위로 처리했을 패, NO와 PGEr 생성에 관여하는 iNOS꽈 COX-2발현이 용량의존적으로 억제되었으며 iNOS의 경우 세포단계에서도 용량의존적으로 억제되었다. 뿐만 아니라 curcumin은 I~SrM 범위에서 염증반응을 매개하는 IL-1 및 U-6의 생성을 용량의존적으로 억제하였다. 전사주즐인자인 NF-rB는 ploinffarnmatory cytokine인 TNF-α, a-1, IL-6 및 iNOS와 COX-2등의 발현을 조절하는 것으로 알려져 있는데, curcumin이 NF-rB의 활성화를 억제하는 것으로 보아 LPS 와 IFN-γ로 활성화된 microglia 모델에서 curcumin의 항염증효과는 NF-rB pathu~·ay를 통하여 나타나는 겄으로 사료된다. -MicrogEa, braf resident macrophages, play a central role in the inflammatory responses of the brain and are activated in brain injuries and several neurodegenerative6seases such as Alzhehner's and Huntington's disease, thereby aggravating the course o(these diseases. We previ()usly repofed that curcunBin (1 ~8#M) inhibited tlte release ofinflammatory mediators such as nitric oxide (NO), prostaglandin Ef (PGEa), Tumor necrosisfactor- α (TNF-o) in Ipopolysacchafde (LPS) plus interferon- γ (HN-γ)-stimulatedmicroglia. h thiE sttdy, we examined whether curcuBCn can inhibit the production ofFfoinflarnmatdry mecators by suppressing the activation of Nuclear factor- f B (NP~ rE).Curcunfn inRbited other inflammatory cytokines, InterBeukin-1 (TL-1) and Interleukin-6 (t-6)in a dose-dependent manner, and also suppressed the induction of both inducible nitricoxide synthase fHOS) and cyclooxygenase-2 (COX-2), which catalyses the conversion ofarachidonic acid to prostagtandins. In addition, curcumin inhibited the activation of NF- f B,which controls the expresslon of a wide variety of genes active in inflammation that includecytokines (e.g., U-1, T.fF- f , IL-5), enzymes (e.g., iNOS, COX-2). Antiinflammatory effectof curcumin in cuthlred m:icroglial model seems to be mediated through NF- f B pathway,suggesting that may havc a significant impact in the prevention of immune-mediatedneurodeg enerativ e disordors.

Effects of Curcumin on the Modulation of Microglial Activation(Ⅲ)

Jung, ki Kyung,Lee, Hae Sung,Kim, Tae Gyun,Kang, Ju Hye,Cho, Mi Young,Kim, Seung Hee,Hong, Sungyoul,Kang, Seog Youn 식품의약품안전청 2001 식품의약품안전청 연보 Vol.5 No.-

노인성 치때의 원인물질로 추정되는 Af뀁타이드와 IFN- r로 운도된 microglia의 활성화를 카레의 주성분인 curcumin이 이를 억제하는지 알아보았으며, 또한 도파민에 의해 부분적으로 손상된 신경세포가 활성화된 micro잃.ia회부터 생성된 NO에 의해 손상정도가 증가하는지를 밝히고, curcumin이 NO 캥성을 막제하여 손긍된 신경세포를 보호할 수 있는지를 연구하였다. 생후 0일에서 』일된 rat의 데뇌피질로부터 microgtial cell을 2~3주간 culture하여 얻은 다음 Aβ(25-35)와 IFN-γ로 활성죡를 유도하고 curcLlmin을 2.j~20rH1 범위로 처리했을 패, NO, TNf-o, IL-lr, IL-6의 생성이 용량의존걱으로 억제되었다. 특히 ,4.Ji'(2i-35)와 IFN-r에 의해 활성화된 micro앙la 세포와 도파민에 의해 부분짙으조 손상된 신경세포(CATH.a cell)와의 coculture를 통하여 활성화된 rrllcroglia로부터 생성된 NO가 도과민에 의한 신경세포의 손상을 더욱 더 증가시켰다. 또한 이러한 신경세포의 손상이 J,fl포사멸 (apoptosis)의 형태로 나타남을 밝혔다. 이러한 모델에 curcumin을 적응한 결과 신경세포의 손상이 감소됨을 알 수 있었다. 따라서, 이러한 결과는 curcumin이 Aβ(23-3i)와 IFh- r로 microglia의 확성화를 유도했을 때 생성되는 NO를 억제함으로서 부분적으로 신경J,11포를 보호할 수 있음을 시사한다. Microglia, brain resident macrophages, play a central role in the inflammatory responses of the brain and are activated in brain injuries and several neurodegenerative diseases such as Alzheimer's and Huntigton's disease, thereby aggravating the course of these diseases. In this study we investigated whether curcumin, which is a major component of turmeric (Curcuma longa) and is known as antiinflammatory and antioxidant material, can inhibit production of inflammatory factors in amyloid β(Aβ(25-35)) and interferon-γ-stimulated microglia. Curcumin inhibited production of these factors in a dose dependent manner and also dexamethasone (DEX) inhibited production of them. Continuously, we examined whether curcumin can protect the partially dopamine-damaged neuron through suppression of the production of NO in Aβ(25-35) and interferon-γ-stimulated microglia using potentiation of CATH.a cell death induced by dopamine. Curcumin reduced CATH.a cell death by dopamine level in co-culture with immunostimulated microglia. iNOS inhibitor, NMMA and DEX also reduced CATH.a cell death. Furthermore, both curcumin and NMMA reduced apoptotic death of CATH.a cells in DAPI staining and DNA fragmentation experiments. This result suggest that curcumin can protect neuron in part through suppression of NO produced from Aβ(25-35) plus IFN-γ-stimulated microglia.

돼지 간장 조직내 Protein Methylase Ⅱ 저해제의 정제 및 특성

권명희,정기경,이회영,이향우,홍성렬 ( Myung Hee Kwon,Ki Kyung Jung Hoi,Young Lee,Hyang Woo Lee,Sungyoul Hong ) 생화학분자생물학회 1994 BMB Reports Vol.27 No.6

An inhibitor for protein methylase II (EC 2.1.1.24) was solubilized from porcine liver microsomal fraction by heat treatment, and purified by ultrafiltration, Sephadex G-25 chromatogrnphy, and HPLC using μ-Bondapak C_(18) column. The purified inhibitor was near homogeniety as judged by HPLC. The molecular weight of the inhibitor was estimated to be 1,676 Da by analysis of amino acid composition. And it was revealed that the inhibitor molecule is rich in alanine and glycine. The activity of the inhibitor was not affected by heat treatment up to 100℃ as well as hydrolytic enzymes. The K; value for the protein methylase II which has been purified from porcine spleen was measured to be 1.3 × 10^(-7) M. Inhibition studies showed that the inhibitor was noncompetitive with respect to S-adenosyl-L-methionine (SAM) and activities of several SAM-dependent methylases were also inhibited by the purified inhibitor.