Helicobacter pylori 감염 위점막에서 Peroxisome Proliferator-activated Receptor (PPAR)γ의 발현

손성현 ( Seong Hyun Son ),김형근 ( Hyung Keun Kim ),지정선 ( Jeong Seon Ji ),조영석 ( Young Seok Cho ),김성수 ( Sung Soo Kim ),채현석 ( Hiun Suk Chae ),최명규 ( Myung Gyu Choi ),한석원 ( Sok Won Han ),최규용 ( Kyu Yong Choi ),정 대한소화기학회 2007 대한소화기학회지 Vol.49 No.2

목적: Peroxisome proliferator-activated receptorγ (PPAR γ)는 핵 전사인자로 염증과 악성종양에 관련된 여러 유전자의 발현을 조절한다. PPAR γ는 대장암뿐만 아니라 위암에서도 발현되며, PPAR γ 배위자는 암세포의 분화와 세포자멸사를 유도한다. H. pylori의 지속적인 감염은 만성위염과 소화성 궤양을 일으키고, 세포 전환율을 변화시킨다. 또한 H. pylori는 위암의 주요한 원인 인자이다. 이에 저자들은 H. pylori 감염이 위점막에서 PPAR γ 발현에 미치는 영향에 대해 알아보고자 하였다. 대상 및 방법: 상부위장관내시경검사를 시행한 39명에서 위점막 검체를 얻었다. H. pylori 감염 여부 확인을 위한 신속요소분해효소검사와 조직 검사를 시행하여 H. pylori 감염 정도와 염증세포들의 침윤 정도를 확인하였다. 면역조직화학염색을 시행하여 위점막 검체에서 PPAR γ 단백의 발현 위치, 발현 정도와 강도를 확인하였다. 또한 PPAR γ의 특이 primer를 이용하여 real time PCR을 시행하여 mRNA의 발현 정도를 확인하였다. 결과: PPAR γ 단백은 선와상피세포의 핵에서 발현되었고, 장상피화생 조직과 위암 조직에서도 발현되었다. PPAR γ 단백 발현은 H. pylori 감염 군에서 3.8±0.4, 비감염군에서 2.6±1.0으로 의미있는 차이를 보였다(p=0.012). PPAR γ mRNA 발현은 대장암군에서 H. pylori 감염군과 비감염군에 비하여 유의하게 증가하였으나(p<0.05), H. pylori 감염군과 비감염군에서는 유의한 차이가 없었다(p>0.05). 결론: H. pylori 감염이 위점막에서 PPAR γ 단백 발현을 증가시킴을 확인하였고, PPAR γ가 H. pylori에 의해 유발되는 일련의 염증반응에 중요한 역할을 하는 것으로 생각한다. 추후 이에 대한 더 많은 연구가 필요하다. Background/Aims: Peroxisome proliferator-activated receptor γ (PPARγ), a nuclear transcription factor, plays a critical role in the regulation of gene expression associated with inflammation and cancer. PPAR γ is expressed in human gastric cancer as well as in colon cancer. Activation of PPAR γ by ligand produces pro-apoptotic effect and ameliorate growing of cancer cells. Helicobacter pylori (H. pylori) is a main etiologic agent for gastric inflammation, and raises cell turnover in gastric epithelium. Longstanding infection with this organism is related with the development of non-cardiac gastric cancer. The aim of this study was to investigate the effect of H. pylori on the expression of PPARγ protein and mRNA in chronic gastritis. Methods: Gastric biopsy samples were taken from H. pylori infected (n=18) and non-infected (n=21) patients during endoscopic examination. PPAR γ expressions were assessed by real time polymerase chain reaction and immunohistochemistry. Results: PPAR γ was localized to the nuclei of the foveolar epithelial cells in both infected and non-infected mucosa. PPAR γ protein expression was higher in H. pylori infected patients than in non-infected patients (3.8±0.4 vs. 2.6±1.0, H. pylori infected and non-infected, respectively; p<0.05). However, PPAR γ mRNA levels were not significantly different between the two groups (24±18 vs. 29±25, H. pylori infected and noninfected, respectively). Conclusions: PPAR γ expression is increased in the gastric mucosa of H. pylori infected chronic gastritis, which suggests a certain role of PPARγ in the mucosal inflammatory reaction to H. pylori infection. (Korean J Gastroenterol 2007;49:72-78)

한국인 다낭난소증후군 여성에서 Peroxisome Proliferator-activated Receptor-γ (PPARγ) 유전자다형성

오지영 ( Jee Young Oh ),이혜진 ( Hye Jin Lee ),홍영선 ( Young Sun Hong ),성연아 ( Yeon Ah Sung ),정혜원 ( Hye Won Chung ) 대한당뇨병학회 2007 Diabetes and Metabolism Journal Vol.31 No.6

Pharmacophore Identification for Peroxisome Proliferator-Activated Receptor Gamma Agonists

손영식,이윤호,Chanin Park,Swan Hwang,Songmi Kim,Ayoung Baek,Minky Son,서정근,Hyong-Ha Kim,이근우 대한화학회 2011 Bulletin of the Korean Chemical Society Vol.32 No.1

Peroxisome proliferator-activated receptors (PPARs) are members of nuclear receptors and their activation induces regulation of fatty acid storage and glucose metabolism. Therefore, the PPARγ is a major target for the treatment of type 2 diabetes mellitus. In order to generate pharmacophore model, 1080 known agonists database was constructed and a training set was selected. The Hypo7, selected from 10 hypotheses, contains four features: three hydrogen-bond acceptors (HBA) and one general hydrophobic (HY). This pharmacophore model was validated by using 862 test set compounds with a correlation coefficient of 0.903 between actual and estimated activity. Secondly, CatScramble method was used to verify the model. Hence, the validated Hypo7 was utilized for searching new lead compounds over 238,819 and 54,620 chemical structures in NCI and Maybridge database, respectively. Then the leads were selected by screening based on the pharmacophore model, predictive activity, and Lipinski’s rules. Candidates were obtained and subsequently the binding affinities to PPARγ were investigated by the molecular docking simulations. Finally the best two compounds were presented and would be useful to treat type 2 diabetes.

Peroxisome proliferator activated receptor-γ modulates reactive oxygen species generation and activation of nuclear factor-κB and hypoxia-inducible factor 1α in allergic airway disease of mice

Lee, Kyung Sun,Kim, So Ri,Park, Seoung Ju,Park, Hee Sun,Min, Kyung Hoon,Jin, Sun Mi,Lee, Moon Kyu,Kim, Uh Hyun,Lee, Yong Chul Elsevier 2006 The journal of allergy and clinical immunology Vol.118 No.1

<P><B>Background</B></P><P>Reactive oxygen species (ROSs) play a crucial role in the pathogenesis of airway inflammation. Peroxisome proliferator activated receptor (PPAR)-γ is also involved in airway inflammation. We have demonstrated that the administration of PPARγ agonists or adenovirus carrying PPARγ cDNA (AdPPARγ) reduced bronchial inflammation and airway hyperresponsiveness. However, the effects of PPARγ on ROS generation in conditions associated with airway inflammation have not been clarified.</P><P><B>Objective</B></P><P>This study aimed to investigate the effects of the PPARγ on ROS generation in allergic airway disease of mice.</P><P><B>Methods</B></P><P>We have used a female C57BL/6 mouse model for allergic airway disease to determine the role of PPARγ.</P><P><B>Results</B></P><P>In this study with an ovalbumin-induced murine model of allergic airway disease, the increased ROS generation and the increased expression of T<SUB>H</SUB>2 cell cytokines, adhesion molecules, chemokines, and vascular endothelial growth factor in lungs after ovalbumin inhalation were significantly reduced by the administration of PPARγ agonists or AdPPARγ. We also showed that the increased nuclear factor-κB and hypoxia-inducible factor 1α levels in nuclear protein extracts of lung tissues after ovalbumin inhalation were decreased by the administration of PPARγ agonists or AdPPARγ.</P><P><B>Conclusion</B></P><P>These results indicate that the effects of PPARγ are mediated by the modulation of ROS generation and activation of redox-sensitive transcription factor nuclear factor-κB and HIF-1α in allergic airway disease of mice.</P><P><B>Clinical implications</B></P><P>Thus, these findings provide a pivotal molecular mechanism for the use of PPARγ agonists to prevent and/or treat asthma and other airway inflammatory disorders.</P>

Peroxisome Proliferator-activated Receptor-γ가 단핵세포의 Tumor Necrosis Factor-α 생산에 미치는 영향

권은영,박철민,권재철,김시현,박선희,최수미,이동건,유진홍,최정현 대한감염학회 2010 Infection and Chemotherapy Vol.42 No.5

Background: We evaluated the effects of peroxisome proliferator-activated receptor-γ (PPAR-γ) on the production of tumor necrosis factor-α (TNF-α) and expression of nuclear factor-κB (NF-κB) in stimulated THP-1 cells, a human monocyte cell line. Materials and Methods: We evaluated the cytotoxic effect of 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), one of natural PPAR-γ ligands, using commercial cell proliferation assay. Cells were pretreated with 15d-PGJ2 and then stimulated with lipopolysaccharide (LPS) or lipoteichoic acid (LTA). The amount of TNF-α was measured by using commercial ELISA method. NF-κB activation was evaluated by Western blot analysis. Results: 15d-PGJ2 showed dose-dependent cytotoxic effect on the tested cells after 4 hr of treatment. Stimulation of cells by LPS or LTA induced TNF-αproduction. TNF-α production was markedly decreased in the cells pretreated with 15d-PGJ2compared to cells treated only with LPS or LTA in a dose-dependent manner. Pretreatment of 15d-PGJ2 reduced LPS or LTA induced NF-κB expression in the nuclear extracts of THP-1 cells. Conclusion: 15d-PGJ2 pretreatment decreased TNF-α production from the THP-1cells stimulated by LPS or LTA, and this assumed to be associated with inhibition of NF-κB activation.

Peroxisome Proliferator-activated Receptor${\gamma}$ Is Involved in Weaning to Estrus of Primiparous Sows by Regulating the Expression of Hormone Genes in Hypothalamus-pituitary-ovary Axis

Kong, L.J.,Wang, A.G.,Fu, J.L.,Lai, CH.H.,Wang, X.F.,Lin, H.CH. Asian Australasian Association of Animal Productio 2007 Animal Bioscience Vol.20 No.3

The objective of this study was to determine whether peroxisome proliferator-activated receptor ${\gamma}$(PPAR${\gamma}$ is involved in the regulation of weaning to estrus of primiparous sows. Twelve sows composed of 6 groups of 2 full-sibs in a similar age (325.2 d), body weight (BW; 152.4 kg) and backfat thickness (BFT; 27.0 mm) at start of lactation, were allocated to accept 31 MJ (restricted group, R-group) or 53 MJ (control group, C-group) DE/d treatment, respectively. The experimental results indicated that the low energy intake resulted in excessive losses of BW and BFT during lactation in R-group sows, which may be related to decrease of serum 15-deoxy-${\Delta}^{12,14}$-prostaglandin $J_2$ (15d-$PGJ_2$), a ligand of PPAR${\gamma}$ The obvious peak and the frequency of LH, FSH and estradiol ($E_2$) were only observed in C-group sows. Except for $E_2$ at d 1 and 2, serum FSH, LH and $E_2$ concentrations in R-group were lower than those in C-group sows after weaning. However, the serum progesterone ($P_4$) level in R-group sows was always more than that in C-group. The expression abundances of PPAR${\gamma}$and GnRH receptor (GnRH-R) in pituitary, FSH receptor (FSH-R), LH receptor (LH-R), estrogen receptor (ES-R) and aromatase in ovary of anestrous sows were lower than those of estrous sows. Neither the BFT nor the BW was associated with the mRNA abundance of PPAR${\gamma}$in hypothalamus during lactation. Expressions of PPAR${\gamma}$in pituitary and ovary were affected evidently by the BFT changes and only by the loss of BW of sows during and after lactation. Furthermore, PPAR${\gamma}$mRNA level in ovary was significantly related to the expression abundances of GnRH-R, FSH-R, ES-R and aromatase, and GnRH-R was obviously associated with PPAR${\gamma}$expression in pituitary. However, PPAR${\gamma}$expression in hypothalamus likely has no effects on these genes expression and no obvious difference for all sows. Not serum $E_2$ or $P_4$ alone but the ratios of $E_2$ to $P_4$ and 15d-$PGJ_2$ to $P_4$, and serum FSH and LH were evidently related to PPAR${\gamma}$expression in pituitary and ovary. It is concluded that PPAR${\gamma}$is associated with body conditions, reproduction hormones and their receptor expression, which affected the functions of pituitary and ovary and ultimately the estrus after weaning of primiparous sows.

Peroxisome Proliferator-activated Receptor γ Is Not Associated with Adipogenesis in Female Mice

Michung Yoon,Sunhyo Jeong 대한의생명과학회 2008 Biomedical Science Letters Vol.14 No.3

The peroxisome proliferator-activated receptor γ (PPARγ) plays a central role in adipogenesis and lipid storage. The PPARγ 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 PPARγ 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 PPARγ 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 PPARγ and its target genes as well as adipocyte-specific genes in parametrial adipose tissue. These results suggest that PPARγ 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.

인슐린 비의존형 당뇨병 및 비만증 환자에서의 PPARγ2 유전자 다형성

오승준(Seung Joon Oh),강성이(Sung Yi Kang),김영설(Young Seol Kim),김덕윤(Deog Yoon Kim),우정택,김성운(Sung Woon Kim),양인명(In Myung Yang),김진우(Jin Woo Kim),최영길(Young Kil Choi),박혜순(He Soon Park),팽정령(Jung Ryung Paeng) 대한내과학회 2000 대한내과학회지 Vol.59 No.2

Background : Peroxisome proliferator activated receptor-gamma (PPAR-γ) is a nuclear receptor that regulate adipocyte differentiation and modulate intracellular insulin-signaling events. As such, PPARγ is a candidate gene for several human disorders including obesity and type 2 diabetes mellitus. The objective of our study was to examine the relationship between genetic variation of PPARγ2 and diabetes and obesity in Korean subjects. Methods : We studied 99 subjects with type 2 diabetes mellitus, 128 obesity patients and 97 controls. Screening for mutation at codon 12 and 115 of PPARγ2 were carried out by PCR-RFLP analyses. Statistical significance was evaluated by Chi-square test. Results : The allele frequency of the Pro12Ala PPARγ2 variant were 0.05 in controls, 0.06 in type 2 diabetes group, and 0.07 in obesity group (p=0.47). Pro115Gln variant were only proline homozygote in all groups. Genotype frequencies were also similar and conformed to expectations of the Hardy-Weinberg rule. The presence of PPARγ2 gene variant was no associated with concentrations of total cholesterol, triglyceride, HDL-cholesterol, and also with fasting glucose. Conclusion : We concluded that the Pro12Ala and Pro115Gln PPARγ2 missense mutation may not be associated with type 2 diabetes mellitus and obesity in Korean patients.(Korean J Med 59:132-141, 2000)

Peroxisome Proliferator-Activated Receptor-γ Gene Expression and Its Association with Oxidative Stress in Patients with Metabolic Syndrome

Mehdi Hatami,Massoud Saidijam,Reza Yadegarzari,Shiva Borzuei,Alireza Soltanian,Marzieh Safi Arian,Mohammad Taghi Goodarzi 전남대학교 의과학연구소 2016 전남의대학술지 Vol.52 No.3

Regulation of the peroxisome proliferator-activated receptor-γ (PPAR-γ) gene plays an important role in controlling the metabolism of lipids and inflammatory processes. Therefore, it can be associated with the pathogenesis of metabolic syndrome (MetS). The purpose of this study was to determine the expression of this gene in peripheral blood mononuclear cells (PBMC) in patients with metabolic syndrome. Using real-time polymerase chain reaction (PCR), mRNA expression of PPAR-γ was found in PBMC from 37 subjects with MetS and 30 healthy controls. Serum levels of glucose and lipid profiles were measured. The total antioxidant capacity (TAC) was measured using the ferric reducing ability of plasma (FRAP) test. Malondialdehyde (MDA) was determined using a fluorimetric method. Total oxidant status (TOS) in serum was assayed according to oxidation of ferric to ferrous in the presence of methyl orange. Super oxide dismutase (SOD) activity was measured using a Randox kit. Expression of PPAR-γ gene was significantly increased in patients with MetS compared to the control subjects (p=0.002). There was no difference in serum levels of TAC, MDA and SOD between the two study groups, but a significant difference was observed in the TOS (p=0.03). Serum levels of triglycerides and glucose were significantly higher in subjects with MetS. According to the results of our study, an increase in the expression of PPAR-γ in subjects with MetS indicated a possible role of PPAR-γ in the pathogenesis of this disease.

3T3-L1 지방전구세포에서 청가시덩굴 추출물의 항비만 활성

박서현,이정아,홍성수,안은경 한국응용생명화학회 2023 Journal of Applied Biological Chemistry (J. Appl. Vol.66 No.-

Smilax sieboldii is one of the Smilax species. A number of Smilax plants have multiple physiologically-active components and anti-inflammatory/anti-oxidant effects. Antiobesity effects induced by Smilax sieboldii have not been reported. In this study, we investigated the effects and molecular mechanisms of anti-obesity activity of 70% ethanol Smilax sieboldii extract (SSE). The anti-obesity effect of SSE was determined using 3T3-L1 adipocytes. We confirmed that SSE was not cytotoxic to murine 3T3-L1 preadipocytes, we evaluated SSE dosedependently decreased the accumulation of lipids via an Oil Red O assay and triglyceride assay. These anti-obesity activities of SSE were mediated by the inhibition of adipogenesis-related marker genes (peroxisome proliferator activated receptor-γ, CCAATenhancer- binding protein α, and SREBP1c) and lipogenesisrelated marker genes (fatty acid synthase and aP2). These results suggest that SSE has the potential to exert anti-obesity and antihyperlipidemia effects by regulating adipogenic transcription factors and inhibiting the expression of adipogenic markers.