• 제목/요약/키워드: Wy-14,643

검색결과 3건 처리시간 0.021초

Nuclear Receptor PPARα Agonist Wy-14,643 Ameliorates Hepatic Cell Death in Hepatic IKKβ-Deficient Mice

  • Kim, Taehyeong;Wahyudi, Lilik Duwi;Gonzalez, Frank J.;Kim, Jung-Hwan
    • Biomolecules & Therapeutics
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    • 제25권5호
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    • pp.504-510
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    • 2017
  • Inhibitor of nuclear factor kappa-B kinase beta ($IKK{\beta}$) plays a critical role in cell proliferation and inflammation in various cells by activating $NF-{\kappa}B$ signaling. However, the interrelationship between peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) and $IKK{\beta}$ in cell proliferation is not clear. In this study, we investigated the possible role of $PPAR{\alpha}$ in the hepatic cell death in the absence of $IKK{\beta}$ gene using liver-specific Ikkb-null ($Ikkb^{F/F-AlbCre}$) mice. To examine the function of $PPAR{\alpha}$ activation in hepatic cell death, wild-type ($Ikkb^{F/F}$) and $Ikkb^{F/F-AlbCre}$ mice were treated with $PPAR{\alpha}$ agonist Wy-14,643 (0.1% w/w chow diet) for two weeks. As a result of Wy-14,643 treatment, apoptotic markers including caspase-3 cleavage, poly (ADP-ribose) polymerase (PARP) cleavage and TUNEL-positive staining were significantly decreased in the $Ikkb^{F/F-AlbCre}$ mice. Surprisingly, Wy-14,643 increased the phosphorylation of p65 and STAT3 in both Ikkb and $Ikkb^{F/F-AlbCre}$ mice. Furthermore, BrdU-positive cells were significantly increased in both groups after treatment with Wy-14,643. Our results suggested that $IKK{\beta}-derived$ hepatic apoptosis could be altered by $PPAR{\alpha}$ activation in conjunction with activation of $NF-{\kappa}B$ and STAT3 signaling.

Adenophorae Radix 뿌리 추출물에 의한 Keratinocyte의 분화 및 피부장벽 기능에 대한 연구 (Study on Keratinocyte Differentiation and Skin Barrier Function of Adeonphorae Radix Root Extracts)

  • 남개원
    • 대한화장품학회지
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    • 제43권4호
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    • pp.329-335
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    • 2017
  • Triterpenoid, saponin, 전분 등이 함유되어 있는 것으로 알려진 Adenophorae radix (A. radix)의 뿌리 추출물을 이용하여 각질형성세포의 분화와 피부장벽기능에 대한 연구를 수행하였다. A. radix의 뿌리 추출물은 CV-1 세포를 이용하여 $PPAR{\alpha}$ 발현을 살펴본 결과, Wy-14,643 $0.5-1.0{\mu}M$ 수준의 발현양을 나타내었다. 인체 각질형성 세포주(HaCaT)와 각질형성세포(nomal human keratinocyte)에 대한 각질형성능(cornified envelop formation, CE)은 대조군에 비해 통계적으로 유의한 증가를 보였다. HaCaT 세포에 A. radix의 뿌리 추출물 처리하였을 때, transglutaminase (TGase-1)의 유의적 증가를 보였다. A. radix의 뿌리 추출물을 함유한 간단한 화장품 제형을 약 2주간에 걸쳐 임상시험을 실시한 결과, TEWL의 유의적 감소와 수분량의 증가를 살펴볼 수 있었으며, 하박 내측에서 지질을 추출하여 세라마이드를 분석한 결과 통계적으로 유의한 증가를 관찰할 수 있었다. 이를 통하여 A. radix의 뿌리 추출물을 건조피부나 아토피 등의 피부질환과 관련된 질환의 예방 및 치료제로 사용될 수 있을 것이다.

The Korean Traditional Medicine Gyeongshingangjeehwan Reduces Lipid Accumulation in Skeletal Muscle and C2C12 Cells

  • Yoon, Mi-Chung
    • 대한의생명과학회지
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    • 제17권4호
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    • pp.283-289
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    • 2011
  • Our previous study demonstrated that the Korean traditional medicine Gyeongshingangjeehwan (GGEx) activates AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) critical for fatty acid oxidation in skeletal muscle and C2C12 skeletal muscle cells. Thus, we examined whether GGEx can reduce lipid accumulation in these cells and tissues. After obese and type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats were treated with GGEx, we studied the effects of GGEx on skeletal muscle lipid accumulation. The effects of GGEx and/or the AMPK inhibitor compound C on lipid accumulation and expression of AMPK and $PPAR{\alpha}$ were measured in C2C12 skeletal muscle cells. Compared with lean Long-Evans Tokushima Otsuka rats, obese OLETF rats had increased triglyceride droplets. However, administration of GGEx to OLETF rats for 8 weeks significantly decreased triglyceride droplets in skeletal muscle. Consistent with the $in$ $vivo$ data, GGEx inhibited lipid accumulation, the degree of which was comparable to Wy14,643, the potent activator of $PPAR{\alpha}$. GGEx also increased skeletal muscle mRNA levels of AMPK${\alpha}1$, AMPK${\alpha}2$, and $PPAR{\alpha}$. However, compound C inhibited these effects in C2C12 cells. These results suggest that GGEx suppresses skeletal muscle lipid accumulation and this process may be mediated by AMPK and $PPAR{\alpha}$ activation.