• 제목/요약/키워드: GADD45

검색결과 28건 처리시간 0.019초

Antioxidant Activity and Its Mechanism of Paeonia lactiflora Pall Extract

  • Heo, Jee-In;Kim, Jeong-Hyeon;Lee, Jeong-Min;Kim, Sung-Chan;Park, Jae-Bong;Kim, Jaebong;Lee, Jae-Yong
    • Natural Product Sciences
    • /
    • 제19권1호
    • /
    • pp.49-53
    • /
    • 2013
  • Paeonia lactiflora Pall (PL) has been used as a traditional herbal medicine in China, Korea, and Japan for more 1,200 years. PL has reported to have antioxidant activity and protective effect of cells from oxidative stress, although the mechanism has not been verified. FOXO3a is a transcription factor that binds to its target gene's consensus FOXO binding site. FOXO3a protein modulates the various biological functions including cell cycle control, apoptosis, DNA repair, and ROS detoxification. Therefore, FOXO3a activity is associated with cancer, aging, diabetes, infertility, neurodegeneration, and immune system dysfunction. Here we found that FOXO3a was activated by PL extract. Transcriptional target genes such as MnSOD, p27, and GADD45 were activated by PL extract. Protein levels of MnSOD and catalase were increased, consequently, ROS level was reduced in HEF cells by PL extract. These findings suggest that PL extract has an antioxidant activity through FOXO activation and thereby activation of FOXO target genes, MnSOD and catalase.

Assessment of Biomarkers in Acetaminophen-Induced Hepatic Toxicity by siRNA

  • Kang, Jin-Seok;Yum, Young-Na;Kim, Joo-Hwan;Park, Sue-Nie
    • Biomolecules & Therapeutics
    • /
    • 제17권4호
    • /
    • pp.438-445
    • /
    • 2009
  • We investigated global gene expression from both mouse liver and mouse hepatic cell lines treated with acetaminophen (APAP) in order to compare in vivo and in vitro profiles and to assess the feasibility of the two systems. During our analyses of gene expression profiles, we picked up several down-regulated genes, such as the cytochrome P450 family 51 (Cyp51), sulfotransferase family cytosolic 1C member 2 (Sult1c2), 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (Hmgcs1), and several genes that were up-regulated by APAP, such as growth arrest and DNA-damage-inducible 45 alpha (Gadd45a), transformation related protein 53 inducible nuclear protein 1 (Trp53inp1) and zinc finger protein 688 (Zfp688). For validation of gene function, synthesized short interfering RNAs (siRNAs) for these genes were transfected in a mouse hepatic cell line, BNL CL.2, for investigation of cell viability and mRNA expression level. We found that siRNA transfection of these genes induced down-regulation of respective mRNA expression and decreased cell viability. siRNA transfection for Cyp51 and others induced morphological alterations, such as membrane thickening and nuclear condensation. Taken together, siRNA transfection of these six genes decreased cell viability and induced alteration in cellular morphology, along with effective inhibition of respective mRNA, suggesting that these genes could be associated with APAP-induced toxicity. Furthermore, these genes may be used in the investigation of hepatotoxicity, for better understanding of its mechanism.

Early Gene Expression in Mouse Spleen Cells after Exposure to Nickel Acetate

  • Koh Jae-Ki;Kim Woo-Hyoung;Lee Chang-Ho;Nam Hae-Seon;Kim Sung-Ho;Woo Kee-Min;Lee Sang-Han
    • Toxicological Research
    • /
    • 제22권2호
    • /
    • pp.95-102
    • /
    • 2006
  • Exposure to soluble nickel compound produces toxic effects on immune system, but the mechanism of action remains to be elucidated. Differential gene expression was studied to understand the potential molecular mechanism responsible for acute toxicity induced by nickel acetate in spleen cells. We exposed mouse spleen cells to nickel acetate with a nontoxic dose ($40{\mu}M$) and then extracted total RNA at 6 h and 12 h after exposure. The RNA was hybridized onto 10K mouse oligonucleotide microarrays, and data were analyzed using GeneSpring 7.1. Nickel had a modest effects on expression of many genes, in the range of 1.3-3 fold. The expression profile showed time-dependent changes in expression levels of differentially expressed genes, including some important genes related to cell cycle, apoptosis and DNA repair. In hierarchical cluster analysis of duplicate experiments, 111 genes were screened out. Out of these, 44 genes showing time- dependent up-regulation (>1.5 fold) and 38 genes showing down-regulation (>1.5 fold) at all time points were chosen for further analysis. The change in the expression of three genes (GPX1, GADD45B and FAIM) after nickel treatment was validated using RT-PCR. As a rule, a number of genes appear to be coordinately regulated between cell survival and cell death from nickel toxicity. In conclusion, changes in the gene profile in the spleen after nickel treatment are complex and genes with diverse functions are modulated. These findings will be contributed to the understanding of the complicated biological effects of nickel.

백굴채 추출물의 항산화 활성과 기전 (Antioxidant Activity and Its Mechanism of Chelidonium majus Extract)

  • 허지인;김정현;이정민;임순성;김성찬;박재봉;김재봉;이재용
    • 한국약용작물학회지
    • /
    • 제21권2호
    • /
    • pp.136-141
    • /
    • 2013
  • Chelidonium majus (CM) contains several isoquinoline alkaloids that have been reported to have various biological activities such as anti-inflammatory, antimicrobial, antioxidant, immune-modulatory, and antitumoral. It has been reported that the extract of CM had an antioxidant potential, however the mechanism has not been verified. In this study, we found that CM extract activated FOXO3a. FOXO3a is a transcription factor that involved in various biological processes such as cell cycle arrest, apoptosis, DNA repair, and ROS detoxification. Transcriptional activities of FOXO3a were regulated by post-translational modifications including phosphorylation, acetylation, and ubiquitination. Protein level of FOXO3a was increased by CM extract. Promoter activities of FOXO-transcriptional target genes such as MnSOD, p27 and GADD45 were activated by CM extract in a dose dependent manner. In addition, protein level of MnSOD, major antioxidant enzyme, was increased by CM extract. Thereby ROS level was decreased by CM in old HEF cells. These results suggest that CM extract has an antioxidant activity through FOXO activation.

Analysis of Genes Regulated by HSP90 Inhibitor Geldanamycin in Neurons

  • ;;권오유
    • 대한의생명과학회지
    • /
    • 제15권1호
    • /
    • pp.97-99
    • /
    • 2009
  • Geldanamycin is a benzoquinone ansamycin antibiotic that binds to cytosol HSP90 (Heat Shock Protein 90) and changes its biological function. HSP90 is involved in the intracellular important roles for the regulation of the cell cycle, cell growth, cell survival, apoptosis, angiogenesis and oncogenesis. To identify genes expressed during geldanamycin treatment against neurons of rats (PC12 cells), DNA microarray method was used. We have isolated 2 gene groups (up-or down-regulated genes) which are geldanamycin differentially expressed in neurons. Granzyme B is the gene most significantly increased among 204 up-regulated genes (more than 2 fold over-expression) and Chemokine (C-C motif) ligand 20 is the gene most dramatically decreased among 491 down-regulated genes (more than 2 fold down-expression). The gene increased expression of Cxc110, Cyp11a1, Gadd45a, Gja1, Gpx2, Ifua4, Inpp5e, Sox4, and Stip1 are involved stress-response gene, and Cryab, Dnaja1, Hspa1a, Hspa8, Hspca, Hspcb, Hspd1, Hspd1, and Hsph1 are strongly associated with protein folding. Cell cycle associated genes (Bc13, Brca2, Ccnf, Cdk2, Ddit3, Dusp6, E2f1, Illa, and Junb) and inflammatory response associated genes (Cc12, Cc120, Cxc12, Il23a, Nos2, Nppb, Tgfb1, Tlr2, and Tnt) are down-regulated more than 2 times by geldanamycin treatment. We found that geldanamycin is related to expression of many genes associated with stress response, protein folding, cell cycle, and inflammation by DNA microarray analysis. Further experimental molecular studies will be needed to figure out the exact biological function of various genes described above and the physiological change of neuronal cells by geldanamycin. The resulting data will give the one of the good clues for understanding of geldanamycin under molecular level in the neurons.

  • PDF

Constitutive Androstane Receptor (CAR)의 활성, 에너지 대사 및 세포의 증식과 사멸의 조절에 대한 CAR의 cross-talk 기전 (The Cross-talk Mechanisms of Constitutive Androstane Receptor (CAR) in the Regulation of its Activity, Energy Metabolism, Cellular Proliferation and Apoptosis)

  • 민계식
    • 생명과학회지
    • /
    • 제30권2호
    • /
    • pp.211-220
    • /
    • 2020
  • CAR의 활성은 리간드 결합 뿐만 아니라, 세포외신호전달 경로를 통한 관련 조절인자들의 인산화, 전사 조절인자들과의 상호작용, 그리고 coactivators 및 corepressors의 동원, 분해 및 발현 등에 의해 조절되며, 이러한 CAR의 활성 조절은 또한 외인성 화학물질과 에너지 대사, 세포의 증식 및 사멸을 포함한 다양한 생리적 항상성 조절에 영향을 미친다. CAR는 ERK1/2의 신호전달경로에 의해 인산화되어 Hsp-90/CCRP와 복합체를 형성하여 세포질 내에 잔류하는 반면, PB는 ERK1/2를 억제하여 downstream 신호전달 조절인자들의 탈인산화를 유발하고, 활성화된 RACK-1/PP2A를 동원하여 CAR를 탈인산화 함으로써 핵 이동 및 전사 활성을 유도한다. CAR의 활성은 FoxO1 및 PGC-1α와의 cross-talk을 통하여 각각 전사 활성 억제와 ubiquitination을 통한 단백질 분해를 유도하여 당합성과정에 관여하는 PEPCK 및 G6Pase 유전자의 발현을 억제한다. CAR에 의한 지방의 합성과 산화 조절은 각각 PPARγ 및 PPARα와의 cross-talk에 의한 PGC-1α의 분해와 CPT-1의 발현 억제 또는 PGC-1α와의 결합을 통해 지방 합성 유전자의 발현 억제와 조직 특이적 산화 억제 또는 촉진으로 이루어진다. CAR는 FoxO1의 억제를 통한 p21의 발현 억제와 cyclin D1의 발현을 유도하여 세포 증식을 촉진하는 반면, GADD45B의 발현을 통한 MKK7과 JNK1의 활성을 억제하여 세포 사멸을 억제한다. 결론적으로, CAR는 세포외신호전달 경로와 세포내 조절인자들과의 다양한 상호작용을 통하여 외인성 화학물질의 대사뿐만 아니라 에너지 대사 및 세포의 성장과 사멸의 조절을 통한 항상성 유지에 관여한다.

키토산 기반 나노방출제어시스템의 세포주기진행 유전자 발현 증진 효과 및 기전 (Effect and mechanism of chitosan-based nano-controlled release system on the promotion of cell cycle progression gene expression)

  • 이원중;박광만;이성복;황유정;이석원
    • 대한치과보철학회지
    • /
    • 제59권4호
    • /
    • pp.379-394
    • /
    • 2021
  • 목적: 이전 연구에서 치은섬유아세포 혹은 성견 구개 연조직에 trichloroacetic acid (TCA)를 적용하는 것이 세포주기진행 유전자 발현의 변화를 일으키는 것으로 밝혀졌다. 이에 따라 본 연구에서는, hydrophobically modified glycol chitosan (HGC)기반의 나노방출제어시스템을 이용한 TCA 및 상피세포성장인자(EGF)의 순차적 방출시스템에서 이 효과를 검증하기 위하여 다양한 세포주기진행 유전자들의 발현을 규명하였다. 재료 및 방법: TCA와 EGF를 담지하는 HGC기반 나노방출제어시스템을 제작하였다. 실험군은 대조군(CON); TCA-담지형 나노방출제어시스템 투여군(EXP1); TCA- 및 EGF-담지형 나노방출제어시스템 투여군(EXP2)으로 정의되었다. 24시간 및 48시간 배양 시 37개 세포주기 유전자들의 발현을 분석하였다. 영향인자로서의 유전자 및 상관관계에 대해서도 분석하였다. 결과: Cyclins (CCNDs), cell division cycles (CDCs), cyclin-dependent kinases (CDKs), E2F transcription factors (E2Fs), extracellular signal-regulated kinases (ERKs)와 같은 다수의 유전자들과 기타 다른 세포주기 유전자들의 발현이 EXP1과 EXP2에서 상향조절되었다. E2F4, E2F5, GADD45G와 같은 세포주기차단 유전자들의 발현도 상향조절되었으나, 또다른 세포주기차단 유전자인 SMAD4의 발현은 하향조절되었다. 다중회귀분석에서 CCNA2, CDK4 그리고 ANAPC4가 ERK 유전자 발현에 가장 영향력 있는 유전자로 선정되었다. 결론: HGC기반 순차적 나노방출제어시스템을 이용한 TCA 및 EGF의 적용은 다양한 세포주기진행 유전자들의 발현을 상향조절함이 밝혀졌고, 이를 토대로 한 구강연조직증대시스템 개발의 가능성이 확보되었다.

ATF3 발현을 통한 curcumin의 대장암 세포 성장 저해 (Curcumin Inhibits Cell Proliferation of Human Colorectal HCT116 Cells through Up-Regulation of Activating Transcription Factor 3 (ATF3))

  • 김효림;손정빈;임승현;김종식
    • 생명과학회지
    • /
    • 제22권4호
    • /
    • pp.492-498
    • /
    • 2012
  • 파이토케미칼이 암 세포 성장에 미치는 영향을 확인하기 위하여, 대장암 세포주 HCT116에 네 종류의 파이토케미칼을 각각 25 ${\mu}M$의 농도로 처리하였다. 처리한 파이토케미칼 중 curcumin이 가장 강력하게 세포 성장을 억제하였다. 또한 curcumin은 농도의존적으로 세포 성장을 억제하였다. Curcumin에 의한 대장암 세포주 성장 저해 활성에 대한 분자생물학적 기전을 연구하기 위하여 oligo DNA microarray 실험을 수행하였다. 그 결과, 25 ${\mu}M$ curcumin 처리에 의해 2배 이상 발현이 증가된 유전자 137개, 발현이 감소된 유전자 141개를 선별하였다. 발현이 증가된 유전자 중, 세포사멸과 밀접한 관련이 있는 것으로 알려진 유전자 3개를 선택하여, RT-PCR을 통해 이들 유전자의 발현이 감소됨을 확인하였다. 처리한 파이토케미칼 중 curcumin은 가장 강력한 ATF3의 유도자였으며, 농도의존적으로 ATF3의 발현을 증가시켰다. 흥미롭게도, curcumin에 의한 성장 저해는 ATF3-siRNA에 의한 ATF3 유전자 발현감소에 의해 성장이 회복되었다. 또한, ATF3 유전자의 과대발현 후 발현이 변화되는 유전자를 선별한 결과, 세포사멸과 관련된 많은 유전자들이 증가됨을 확인하였다. 결론적으로, 대장암 세포주에서 curcumin에 의한 항 성장활성에 있어서 ATF3 유전자가 중요한 역할을 할 것으로 생각된다.