• International Journal of Oral Biology
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• 제43권1호
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• pp.29-35
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• 2018

It is noted that chalcone derivatives have characteristic diverse pharmacological properties, and that precise evidence has been growing that they could regulate a tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) induced insulin resistance. The purpose of the present investigation is to elucidate the effects of the identified chalcone derivatives on adipogenesis, and to find the underlying mechanism of action in that case. Consequently, we first investigated whether the chalcone derivatives could affect the identified $PPAR{\gamma}$-induced transcriptional activity on the proliferator-activated receptor response elements (PPRE) at target promoters, and find that trans-chalcone most significantly increased the $PPAR{\gamma}$-induced transcriptional activity. Additionally, we confirmed that there were up-regulatory effects of trans-chalcone during the adipogenesis and lipid accumulation, and on the mRNA of adipogenic factors in 3T3-L1 cells. Next, we examined the effect of trans-chalcone on the inhibition induced by $TNF-{\alpha}$ on adipogenesis. To that end, we noted that the treatment with trans-chalcone attenuated the effect of $TNF-{\alpha}$ mediated secretion of various adipokines that are involved in insulin sensitivity. For this reason, we noted that this study clearly demonstrates that trans-chalcone enhanced adipogenesis, in part, by its potent effect on $PPAR{\gamma}$ activation and by its reverse effect on $TNF-{\alpha}$.

• 한국축산식품학회지
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• 제30권5호
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• pp.787-794
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• 2010

Calcium plays a role as a signaling molecule in various cellular events. It has been reported that calcium suppresses adipocyte differentiation only in the early phase of adipogenesis. Herein, we demonstrate that treatment of A23187, a mobilizer of intracellular calcium, on day 4 post adipocyte differentiation could still reduce lipid accumulation in differentiating 3T3-L1 cells for 48 h. In addition, luciferase reporter gene and RT-Q-PCR assays demonstrate that A23187 can selectively inhibit transcriptional activities and expression of PPAR$\gamma$ and LXR$\alpha$, suggesting that A23187 may reduce lipid accumulation in the late phase of adipogenesis via downregulation of PPAR$\gamma$ and LXR$\alpha$ expression and transactivation. Moreover, inhibition of HDAC activity by trichostatin A (TSA) partially blocked A23187-mediated downregulation of transcriptional activities of PPAR$\gamma$ and LXR$\alpha$. Together, our data demonstrate that calcium mobilization inhibits expression and transcriptional activities of PPAR$\gamma$ and LXR$\alpha$, resulting in reduced lipid accumulation in differentiating adipocytes, and thus, mobilization of intracellular calcium in adipocytes may serve as a new preventive and therapeutic approach for obesity.

• 약학회지
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• 제54권2호
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• pp.91-96
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• 2010

Berberine, an isoquinoline alkaloid, has a wide range of pharmacological effects, including anti-inflammation. It has been reported that berberine inhibits experimental colitis through inhibition of IL-8, and that inhibitory effect of berberine on inflammatory cytokine expression is mediated through peroxisome proliferator activated receptor (PPAR)-$\gamma$. In this study, we examined the effects and action mechanism of berberine on the tumor necrosis factor (TNF)-$\alpha$-induced monocyte adhesion to HT29 human colonic epithelial cells, which is commonly used as an in vitro model of inflammatory bowel disease (IBD). Berberine significantly inhibited the TNF-$\alpha$-induced monocyte adhesion to HT29, which is similar to the effect of PDTC, a nuclear factor (NF)-$\kappa$B inhibitor. However, ciglitazone and GW, the ligands of PPAR-$\gamma$, did not suppress the TNF-$\alpha$-induced monocyte adhesion to HT29 cells. In addition, TNF-$\alpha$-induced chemokine expression and NF-$\kappa$B transcriptional activity were significantly inhibited by berberine in a concentration-dependent manner. The results suggest that inhibitory effect of berberine on colitis is mediated through suppression of NF-$\kappa$B and NF-$\kappa$B-dependent chemokine expression.

• 한국식품영양과학회지
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• 제43권7호
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• pp.963-971
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• 2014

본 연구에서는 4주간의 고지방식이와 지구성 운동이 골격근의 PGC-$1{\alpha}$, PPAR-${\gamma}$ 및 인슐린 저항성(glucose uptake, GLUT-4)에 미치는 영향을 분석하였다. 인슐린 민감도 지표인 혈당내성검사에서는 일반식이와 비교하여 고지방식이에서 포도당 투여 후 30분과 60분에서 유의하게 증가하였으며, 운동집단에서는 일반식이와 고지방식이집단에 비해 유의하게 감소한 것을 알 수 있었다. 골격근의 포도당 운반률, PGC-$1{\alpha}$, GLUT-4, PPAR-${\gamma}$의 결과에서는 일반식이에 비해 고지방식이집단에서 감소하는 경향이 나타났으나 통계적으로 유의한 차이가 없는 것으로 나타났다. 그러나 운동집단(저/중/고강도운동)에서는 일반/고지방식이집단과 비교하여 유의하게 증가한 것으로 나타났다. 운동집단의 운동강도 차이에서 GLUT-4와 PPAR-${\gamma}$는 집단 간 유의한 차이가 없는 것으로 나타났다. 그러나 골격근의 포도당 운반률과 PGC-$1{\alpha}$ 단백질 발현은 저/중강도 운동과 비교하여 고강도 운동이 유의하게 증가한 것을 알 수 있었다. 이상의 결과를 종합해 볼 때 4주간의 고지방식이는 whole body의 인슐린 저항성을 발생시켰으나 근육 내 인슐린 저항에는 영향을 미치는 못한 것으로 사료된다. 그러므로 추후 고지방식이의 함량, 섭취 기간 등을 고려한 연구가 필요할 것으로 생각된다. 또한 4주간의 지속적인 지구성 운동이 고지방식이로 인해 발생된 골격근 인슐린 저항성을 감소시키는데 효과적인으로 나타났으나 운동 강도에 따른 골격근의 포도당 운반률, PGC-$1{\alpha}$, GLUT-4, PPAR-${\gamma}$의 변화가 인슐린 저항성이 개선시켰다고 설명하기는 부족한 것으로 판단된다. 그러므로 추후 본 연구의 결과를 바탕으로 운동 형태(운동 기간, 운동강도)에 따른 골격근의 PGC-$1{\alpha}$와 insulin signalling pathway에 대한 세부적인 연구가 필요할 것으로 생각된다.

• 생명과학회지
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• 제19권11호
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• pp.1637-1643
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• 2009

천연생약 자초의 한 성분인 shikonin은 항염증, 항암 및 항비만 등 다양한 분야에 효과를 보여왔다. 이번 연구에서는 shikonin이유도하는 adipogenesis억제 과정에 어떤 인자들이 작용하는지 살펴보았다. Shikonin의 효과에 대한 분자적 메커니즘을 규명하기 위해, real-time PCR을 이용하여 C/EBPs, $PPAR{\gamma}$를 포함한 다양한 adipogenesis 인자들의 mRNA 발현량을 분석하였다. 그 결과, 초기 분화의 주요 조절자인 C/$EBP{\beta}$와 C/$EPB{\delta}$는 shikonin에 의해 거의 변화가 없었으나, 후기 분화의 주요 조절자인 $PPAR{\gamma}$와 C/$EPB{\alpha}$의 mRNA 발현은 유의하게 감소하였다. Shikonin에 의한 adipogenesis억제의 메커니즘을 좀 더 자세히 밝히기 위해 adipogenesis과정의 상위 단계에 위치한 조절자들의 mRNA 발현을 분석하였다. C/$EBP{\beta}$의 상위 조절자인 C/$EBP{\gamma}$, CHOP은 shikonin에 의해 영향을 받지 않았으나, KROX20의 경우 유의하게 감소하였다. 이러한 결과는 Pro-adipogenic 인자인 KROX20의 감소가 C/$EBP{\beta}$에 영향을 주기 보다는 C/$EBP{\beta}$와 독립적으로 그 하위의 인자들에게 영향을 줄 수 있음을 제시한다. $PPAR{\gamma}$의 상위 조절자로 알려져 있는 KLF 들 중에서 pro-adipogenic 인자인 KLF15의 mRNA 발현은 shikonin에 의해 급격히 감소하였으나 anti-adipogenic 인자인 KLF2는 shikonin에 의한 변화가 거의 없었다. 또 다른 pro-adipogenic 인자인 KLF5의 경우, 주로 작용하는 초기 분화에서는 shikonin에 의해 거의 변화가 없었지만, 후기 분화에서는 조금 증가하였다. 이러한 후기 분화에서의 KLF5의 변화는 KLF15에 비해 전체 분화에 크게 영향을 주지 못하는 것 같다. 결론적으로, shikonin은 pro-adipogenic 인자인, KROX20과 KLF15의 조절을 통해 $PPAR{\gamma}$ 및 C/$EPB{\alpha}$의 mRNA 발현을 억제함으로써 지방 세포의 분화를 저해한다고 사료된다.

• Journal of Nutrition and Health
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• 제40권3호
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• pp.221-228
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• 2007

We determined the effects of dietary manipulations on messenger RNA of peroxisome proliferators activated receptor isoforms (i.e., PPAR ${\alpha},\;{\beta}/{\delta},\;{\gamma}$) in red vastus lateralis muscle of rats. Total 16 male Sprague-Dawley rats were used, and animals were divided into one of two dietary conditions: either chow diet group (CHOW; n=8) in which animals were 134 with standard rodent chow (61.8% carbohydrate, 15.7% fat, 22.5% protein) or high fat diet group (FAT n=8) in which animals were fed 24.3% carbohydrate, 52.8% fat, 22.9% protein. At the end of the 8 weeks of experimental period, red vastus lateralis muscle was dissected out from all animals, and PPAR ${\alpha},\;{\beta}/{\delta},\;{\gamma}$ mRNA expression was determined. There was no significant difference in body mass (BM) between CHOW and FAT. As expected, blood glucose and free fatty acid (FFA) concentration was higher in FAT than CHOW (p<0.05), and lactate concentration was significantly lower in FAT compared to CHOW (p<0.05). Insulin concentration tended to higher in FAT than CHOW ($67.2{\pm}21.9\;vs.\;27.0{\pm}5.2$ pmol/L), but it did not reach to the statistical significance. Gene expression of PPAR ${\alpha}$ was not significantly different between CHOW and FAT. It was not also significantly different in PPAR ${\beta}/{\delta}$. Interestingly, expression of mRNA in PPAR ${\gamma}$ however, was markedly depressed in FAT compared to CHOW (approximately 3 fold higher in CHOW; p<0.05). Results obtained from present study implies that PPAR ${\gamma}$ (as compensatory function of PPAR ${\alpha}$ is expressed) possibly exerts another major tuning roles in fatty acid transport, utilization, as well as biosynthesis in skeletal muscle cells. The situations and conditions that can be postulated for this implication need to be further examined.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.14-40
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• 2002

15-Deoxy-${\Delta}^{12, 14}$-prostaglandin $J_2$ (15-deoxy-$PGJ_2$), a naturally occurring ligand activates the peroxisome proliferator-activated $receptor-{\gamma}(PPAR-{\gamma}$). Activation of $PPAR-{\gamma}$ has been found to induce cell differentiation such as adipose cell and macrophage. Here it was investigated whether 15-deoxy-$PGJ_2$ has neuronal cell differentiation and possible underlying molecular mechanisms. Dopaminergic differentiating PC 12 cells treated with 15-deoxy-$PGJ_2$ (0.2 to 1.6 ${\mu}M$) alone showed measurable neurite extension and expression of neurofilament, markers of cell differentiation. However much greater extent of neurite extension and expression of neurofilament was observed in the presence of NGF (50 ng/ml). In parallel with its increasing effect on the neurite extension and expression of neurofilament, 15-deoxy-$PGJ_2$ enhanced NGF-induced p38 MAP kinase expression and its phosphorylation in addition to the activation of transcription factor AP-1 in a dose dependent manner. Moreover, pretreatment of SD 203580, a specific inhibitor of p38 MAP kinase inhibited the promoting effect of 15-deoxy-$PGJ_2$(0.8 ${\mu}M$) on NGF-induced neurite extension. This inhibition correlated well with the ability of SB203580 to inhibit the enhancing effect of 15-deoxy-$PGJ_2$ on the expression of p38 MAP kinase and activation of AP-1, The promoting ability of 15-deoxy-$PGJ_2$ did not occur through $PPAR-{\gamma}$, as synthetic PPAR-${\gamma}$ agonist andantagonist did not change the neurite promoting effect of 15-deoxy-PGJ$_2$. In addition, contrast to other cells (embryonic midbrain and SK-N-MC cells), $PPAR-{\gamma}$ was not expressed in PC-12 cells. Other structure related prostaglandins, PGD$_2$ and $PGE_2$ acting via a cell surface G-protein-coupled receptor (GPCR) did not increase basal or NGF-induced neurite extension. Moreover, GPCR (EP and DP receptor) antagonists did not alter the promoting effect of f 5-deoxy-$PGJ_2$ on neurite extension and activation of p38 MAP kinase, suggesting that the promoting effect of 15-deoxy-$PGJ_2$ may not be mediated GPCR. These data demonstrate that activation of p38 MAP kinase in conjunction with AP-1 single pathway may be important in the promoting activity of 15-deoxy-$PGJ_2$ cells.

• Clinical and Experimental Reproductive Medicine
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• 제40권2호
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• pp.67-75
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• 2013

Objective: To investigate the effect of peroxisome proliferator activated receptor ${\gamma}$(PPAR${\gamma}$) agonist on the cell proliferation properties and expression of human telomerase reverse transcriptase (hTERT) and aromatase in cultured endometrial stromal cell (ESC) from patients with endometriosis. Methods: Human endometrial tissues were obtained from women with endometriosis and healthy women (controls) using endometrial biopsy. Isolated ESCs were cultured and the cell proliferation was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and expression of hTERT, aromatase, and cyclooxygenase (COX)-2 by western blotting according to the addition of rosiglitazone (PPAR${\gamma}$ agonist). Results: We demonstrate that the cultured ESCs of endometriosis showed hTERT protein overexpression and increased cellular proliferation, which was inhibited by rosiglitazone, in a dose-dependent manner. At the same time, PPAR${\gamma}$ agonist also inhibited aromatase and COX-2 expression, resulting in decreased prostaglandin $E_2$ production in the ESCs of endometriosis. Conclusion: This study suggests that PPAR${\gamma}$ agonist plays an inhibitory role in the proliferative properties of eutopic endometrium with endometriosis by down-regulation of hTERT and COX-2 expression; this could be a new treatment target for endometriosis.

• 한국임상수의학회지
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• 제31권6호
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• pp.469-476
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• 2014

본 연구는 염증상태에서의 CLA의 효과와 작용기전을 알아보기 위해 LPS-자극 RAW 264.7 macrophages에 있어 ROS 생성과 TNF-${\alpha}$ 생산, NF-${\kappa}B$ 및 $PPAR{\gamma}$ 활성을 검토하였다. t10c12-CLA는 LPS로 자극하지 않은 비염증시의 RAW 세포에서는 ROS 생성을 증가시켜 TNF-${\alpha}$ 생산을 유도하였으며, 이 효과는 $PPAR{\gamma}$ 활성화에 의존해서 NF-${\kappa}B$ 활성 증가에 의해 매개되었다. 반면, LPS로 자극한 염증조건의 RAW 세포에서는 t10c12-CLA가 $PPAR{\gamma}$ 활성화에 의존하지 않는 경로로 ROS 생성 및 과도한 TNF-${\alpha}$ 생산을 억제하였다. 본 결과로부터 CLA는 ROS 생성을 통해 TNF-${\alpha}$ 생산 및 NF-${\kappa}B$ 활성을 염증 유무에 따라 조절하는 것으로 사료되었다.

• Natural Product Sciences
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• 제28권2호
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• pp.80-88
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• 2022

Colorectal cancer is one of the most common cancers globally, ranking second for the number of cancer-related deaths. Metastasis has been reported as the main cause of death in patients with colorectal cancer. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a transcription factor that functions as a tumor suppressor by inhibiting cellular proliferation, migration, and invasion. In our previous efforts to generate natural product-motivated PPAR-γ ligands, the compounds 1 and 2 were obtained. These compounds activated PPAR-γ and inhibited the migration and invasion of HCT116 colorectal cancer cells, and they were also found to inhibit the epithelial-to-mesenchymal transition, which is a key process in cancer metastasis. Compounds 1 and 2 upregulated expression of the epithelial marker (E-cadherin), and downregulated expression of the mesenchymal marker (N-cadherin) and transcriptional factor (Snail). Therefore, the PPAR-γ agonists 1 and 2 could serve as a valuable model for the study on anti-metastatic leads for the treatment of colorectal cancer.