• KSBB Journal
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• 제25권6호
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• pp.507-512
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• 2010

In this study, we investigated the ability of luteolin, a plant derived flavonoid on hepatocarcinoma cell growth using HepG2 cell culture system. We found that luteolin increased the Smac/DIABLO releases, a mitochondrial protein that potentiates apoptosis. Luteolin also induced either transcriptional activity or expression of PPAR-gamma, a target of cancer growth that PPAR-gamma agonist sensitizes to apoptosis in certain cancer types. To find the possible upstream target molecules of PPAR-gamma activated by luteolin treatment, we used compound C, a specific inhibitor of AMP-activated protein kinase. Pre-treatment of Compound C significantly restored the activation or expression of PPAR-gamma stimulated by luteolin. This result indicated that AMPK signaling might be involved in the activation or expression of PPAR-gamma signaling pathway stimulated by luteolin. Moreover, we also found that luteolin inhibited the insulin-stimulated Akt phosphorylation as well as AICAR, a specific AMPK activator. These results propose that luteolin significantly induces cancer cell death through modulating survival signal pathways such as PPAR-gamma and Akt. AMPK signaling pathway may be an upstream regulator for survival signal pathways such as PPAR-gamma and Akt stimulated by luteolin.

• 대한의생명과학회지
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• 제14권3호
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• pp.139-146
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• 2008

The peroxisome proliferator-activated receptor ${\gamma}$ $(PPAR{\gamma})$ plays a central role in adipogenesis and lipid storage. The $(PPAR{\gamma})$ ligands, thiazolidinediones (TZDs), enhance in vitro adipogenesis in several cell types, but the role of the TZDs on in vivo adipogenesis is still poorly understood. To investigate how $PPAR{\gamma}$ ligand troglitazone regulates adipogenesis in female mice, we examined the effects of the troglitazone on adipose tissue mass, morphological changes of adipocytes, and the expression of $PPAR{\gamma}$ target and adipocyte-specific genes in low fat diet-fed female C57BL/6 mice. Administration of troglitazone for 13 weeks did not change body and total white adipose tissue weights compared with control mice. Troglitazone treatment also did not cause a significant decrease in the average size of adipocytes in parametrial adipose tissue although it is reported to increase the number of small adipocytes in male animals. Troglitazone did not affect the mRNA expression of $PPAR{\gamma}$ and its target genes as well as adipocyte-specific genes in parametrial adipose tissue. These results suggest that $PPAR{\gamma}$ does not seem to be associated with adipogenesis in females with functioning ovaries and that its inability to induce adipogenesis may be due to sex-related factors.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9093-9099
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• 2014

A growing body of evidence suggests that the peroxisome proliferator-activated receptor-gamma ($PPAR{\gamma}$) gene may harbor targets for the chemoprevention of breast cancer. However, it is unclear whether polymorphisms in the $PPAR{\gamma}$ gene are associated with the susceptibility of breast cancer. We performed a candidate gene association study between $PPAR{\gamma}$ polymorphisms and breast cancer and a meta-analysis on the association of breast cancer with selected $PPAR{\gamma}$ variants. Six single nucleotide polymorphisms (SNPs) in the $PPAR{\gamma}$ gene were analyzed among 456 breast cancer patients and 461 controls from the National Cancer Center in Korea. Association between the polymorphisms and breast cancer risk were assessed using the Cochrane-Armitage test for trend and a multivariate logistic regression model. Two SNPs, rs3856806 and rs1801282, had been previously analyzed, thus enabling us to perform pooled analyses on their associations with breast cancer susceptibility. Our findings from the candidate gene association study showed no association between the $PPAR{\gamma}$ gene polymorphisms and breast cancer risk. A meta-analysis combining existing studies and our current study also refuted an association of the $PPAR{\gamma}$ gene with breast cancer. Our findings suggest that the $PPAR{\gamma}$ gene may not harbor variants that alter breast cancer susceptibility, although a moderate sample size might have precluded a decisive conclusion.

• Food Science and Biotechnology
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• 제17권6호
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• pp.1146-1150
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• 2008

Peroxisome proliferator-activated receptor-gamma ($PPAR_{\gamma}$), a member of the nuclear receptor of ligand-activated transcription factors, plays a key role in lipid and glucose metabolism or adipocytes differentiation. A lignan compound was isolated from mace (the aril of Myristica fragrans Houtt.) as a $PPAR_{\gamma}$ ligand, which was identified as fragrin A or 2-(4-allyl-2,6-dimethoxyphenoxy)-1-(4-hydroxy-3-methoxyphenyl)-propane. To ascertain whether fragrin A has $PPAR_{\gamma}$ ligand-binding activity, it was performed that GAL-4/$PPAR_{\gamma}$ transactivation assay. $PPAR_{\gamma}$ ligand-binding activity of fragrin A increased 4.7, 6.6, and 7.3-fold at 3, 5, and $10{\mu}M$, respectively, when compared with a vehicle control. Fragrin A also enhanced adipocytes differentiation and increased the expression of $PPAR_{\gamma}$ target genes such as adipocytes fatty acid-binding protein (aP2), lipoprotein lipase (LPL), and phosphoenol pyruvate carboxykinase (PEPCK). Furthermore, it significantly increased the expression level of glucose transporter 4 (GLUT4). These results indicate that fragrin A can be developed as a $PPAR_{\gamma}$ agonist for the improvement of insulin resistance associated with type 2 diabetes.

• Journal of Gastric Cancer
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• 제6권4호
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• pp.250-256
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• 2006

목적: 최근 Peroxisome-proliferator-activated receptors (PPAR) 의 역할에 대한 관심이 고조되고 있으나 위암에 대한 실제 임상연구는 부족한 실정이다. 이에 저자들은 위암 조직에서의 $PPAR-{\gamma}$의 발현율과 임상적 의의에 대해 분석을 시행하였다. 대상 및 방법: 2001년 1월부터 2005년 12월까지 서울의료원에서 위암으로 근치적수술을 시행 받은 128명을 대상으로 하였다. 적출된 위조직으로 만들어진 파라핀 블록을 이용해 위암조직 125예와 위암주변 정상조직 128예를 채취하여 $PPAR-{\gamma}$ 발현을 면역조직화학염색으로 확인한 후 비교 분석하였다. 결과: 대상 환자의 평균 연령은 61세였으며 남자 84명 (65.6%), 여자 44명(34.4%)으로 1.9 : 1이었다. $PPAR-{\gamma}$ 발현의 양성률은 정상조직 73/128명(57.0%)에 비하여 위암조직에서는 104/128명(81.3%)으로 유의하게 높았다(P<0.001). 위암조직의 분화도에 따른 $PPAR-{\gamma}$ 발현의 차이에서 분화도가 양호한 경우의 양성률(87.0%)에 비해 나쁜 경우 발현율(74.6%)이 낮았으나 통계적 유의성은 없었다(P=0.074). 위암조직에서와 $PPAR-{\gamma}$ 발현 유무와 생존율 사이에 통계적 유의성은 없었으나(P=0.377) 정상조직에서 $PPAR-{\gamma}$의 발현은 단변량 분석에서 유의하게 높은 생존율을 보였다(P=0.003). 5년 생존율과 연관지어 다변량 분석 통계에서 의미가 있었던 것은 UICC TNM 병기뿐이었다(P<0.001). TNM 병기별 5년 생존율은 IA-89.9%, IB-90.0%, II-89.7%, IIIA-41.0%, IIIB-25.9%, IV-14.6% 였다. 결론: 위암조직에서 정상조직에 비하여 $PPAR-{\gamma}$ 발현이 유의하게 높았으며 위암조직의 분화도가 좋을수록 발현율이 높았다. $PPAR-{\gamma}$의 정상조직 내 발현이 단변량 분석상 유의한 생존율 향상이 있었지만 다변량 분석에서는 유의성이 없어 향후 이에 대한 좀더 많은 증례로 유의성을 찾는 연구가 필요할 것으로 생각된다.

• Bulletin of the Korean Chemical Society
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• 제33권5호
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• pp.1475-1479
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• 2012

Human peroxisome proliferator-activated receptor gamma ($hPPAR{\gamma}$) has been implicated in numerous pathologies, including obesity, diabetes, and cancer. In this study, we verified that amentoflavone is an agonist of $hPPAR{\gamma}$ and probed the molecular basis of its action. It was demonstrated that amentoflavone bound $hPPAR{\gamma}$ with high (picomolar) affinity and increased the binding between $hPPAR{\gamma}$ and steroid receptor coactivator-1 (SRC-1) by approximately 4-fold. Based on a docking study, for the first time, we propose a model of amentoflavone and $hPPAR{\gamma}$ binding in which amentoflavone forms three hydrogen bonds with the side chains of His323, Tyr327, and Arg280 in $hPPAR{\gamma}$ and participates in two hydrophobic interactions.

• Biomolecules & Therapeutics
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• 제18권1호
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• pp.77-82
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• 2010

Peroxisome proliferator-activated receptor $\gamma$ (PPAR${\gamma}$) is a ligand-activated transcription factor that is used as a target for anti-diabetic drug development. In a search for novel PPAR${\gamma}$ agonists, the $\beta$-carboxyethyl-rhodanine derivative SP1818 was identified. We report here the characteristics of SP1818 as a selective PPAR${\gamma}$ agonist. In transactivation assays, SP1818 selectively activated PPAR${\gamma}$, but the degree of PPAR${\gamma}$ stimulation was less than with $1{\mu}M$ rosiglitazone. SP1818 also stimulated glucose uptake in a concentration-dependent manner. The adipocyte differentiation markers adiponectin, scavenger receptor CD36 and aP2 were weakly induced by treatment with SP1818, and TRAP220 subunit was specifically recruited into PPAR${\gamma}$ activated by rosiglitazone but not PPAR${\gamma}$ activated by SP1818.

• 한국정보통신학회논문지
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• 제18권2호
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• pp.482-487
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• 2014

본 연구는 testosterone이 지방세포생성에 미치는 영향과 그것에 대한 분자생물학적 조절기전을 역전사-중합효소 연쇄반응과 일시적인 형질전환 분석을 통해 조사하였다. 정소절제수술 마우스(CAST)에 비해 testosterone이 처리된 정소절제수술 마우스(CAST+T)는 백색지방조직 무게와 지방세포 특이유전자($PPAR{\gamma}$와 aP2)의 발현이 감소되었다. In vivo 결과와 일치되게, testosterone 처리는 분화된 3T3-L1세포에서의 triglyceride축적과 지방세포 특이유전자($PPAR{\gamma}$와 aP2)의 발현을 억제시켰다. Testosterone에 의해 활성화된 androgen receptor(AR)는 $PPAR{\gamma}$ transfection에 의해 유도된 luciferase reporter gene 활성을 억제하였다. 따라서 본 연구결과는 testosterone이 AR을 통해 지방세포분화에 대한 $PPAR{\gamma}$의 작용을 억제 조절한다는 것을 시사하고 있다.

• 동의생리병리학회지
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• 제20권6호
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• pp.1593-1597
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• 2006

We hope to evaluate the effects of Gami-Choakwiyeum (GCKY) on the PPAR-${\gamma}$’ in the OVA induced asthma mouse model. Female BALB/c mice, 8 weeks of age and free of murine specific pathogens were used. Mice were sensitized by intraperitoneal injection of OVA emulsified in aluminum hydroxide in a total volume of 200 ${\mu}{\ell}$ on one day and 14 days. On 21, 22, and 23 days after the initial intraperitoneal injection of OVA, the mice were challenged using an ultrasonic nebulizer. GCKY was administered 7 times by oral gavage at 24 hour intervals fromdays 19 after intraperitoneal injection of OVA. Bronchoalveolar lavage was perfromed 72 hours after the last challenge, and total cell numbers in the BAL fluid were counted. Also, the level of PPAR-${\gamma}$ of normal and OVA-induced asthma moused with/without administration of GCKY were measured by Western blot analysis. For the histologic examination, the specimens were stained with hematoxylin 2 and eosin-Y.(H & E). Numbers of total cells were increased significantly at 72 h after OVA inhalation compared with numbers of total cells in the normal and the administration of GCKY. Especially, the increased numbers of eosinophils in BAL fluids after OVA inhalation were significantly increased. However, the numbers of eosinophils reduced by the administration of GCKY. Western blot analysis revealed that PPAR-${\gamma}$ levels in nuclear level were increased slightly after OVA inhalation compared with the levels in the normal group. After the administration of GCKY, PPAR-${\gamma}$ levels in cytosolic and nuclear levels at 72 h after OVA inhalation were markedly increased. On pathologic examination, there were many acute inflammatory cells around the alveoli, bronchioles, and airway lumen of mice with OVA-induced asthma compared with inflammatory cells in the normal group. However, acute inflammatory cells around alveoli, bronchioles, and airway lumen markedly decreased after administration of GCKY, GCKY can increase a PPAR-${\gamma}$ level and could be an effective treatment in asthma patients through the PPAR-${\gamma}$ mechanism for bronchial asthma.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.380.2-380.2
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• 2002

Peroxisome proliferator-activated receptor (PPAR)-$\gamma$ is a nuclear hormone receptor family that plays an important role in the transcriptional regulation of genes in cellular lipid and energy metabolism. In our search for Iigands for PPAR-$\gamma$ from natural resources. two phenylpropanoids. 3.4.5-Trimethoxy cinnamylalcohol (1) and 3.4.5- Trimethoxy cinnamaldehyde (2). were isolated as PPAR-$\gamma$ agonists from the MeOH extracts of Zanthoxylum schinifolium Sieb. & ZUCCo (Rutaceae) by activity-guided fractionation. These two compoundS bind and activated PPAR-$\gamma$ transcriptional activity in a dose dependent manner assessed by ligand-binding assay. While the maximum activities for PPAR-$\gamma$ of these compounds were comparable with that of rosiglitazone. which is currently used in the treatment of Type II diabetes. the potency of these compounds were much weaker than rosiglitazone ($ED_{50}$=t.2$\mu\textrm{M}$) with the $ED_{50}$ values of 9.08 and 4.08 $\mu\textrm{M}$. respectively. To examine the structure-activity relationship of phenylpropanoids. we prepared several phenylpropanoid derivatives and measured the activity. We observed that substituents at 4'- position could playa key role in determining the potency for PPAR-$\gamma$ agonistic activity .