RISS 검색 - 국내학술지논문

무료
기관 내 무료
유료

내보내기
내책장담기
한글로보기

정확도순

내림차순

내림차순

10개씩 출력

1
Muscarinic acetylcholine receptors mediate eIF4B phosphorylation in SNU-407 colon cancer cells

Liu, Ziyu,Cho, Nam Jeong Academic Press 2016 Biochemical and biophysical research communication Vol. No.
- 원문보기
Abstract We have previously shown that muscarinic acetylcholine receptors (mAChRs) promote global protein biosynthesis in SNU-407 colon cancer cells. To gain insight into the molecular mechanisms underlying this event, we examined whether mAChRs regulate the phosphorylation of eIF4B (eukaryotic initiation factor 4B), an essential component of the translation machinery. When SNU-407 cells were treated with the cholinergic agonist carbachol, eIF4B was phosphorylated in a dose- and time-dependent manner. This carbachol effect was almost completely blocked by the muscarinic antagonist atropine, demonstrating that mAChRs specifically mediate the phosphorylation of eIF4B. Carbachol-stimulated eIF4B phosphorylation was significantly reduced by the MEK1/2 inhibitor U0126, indicating that the MEK1/2-ERK1/2 pathway plays an important role in mAChR-mediated eIF4B phosphorylation. However, treating the cells with the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 or the mTORC1 (mammalian target of rapamycin complex 1) inhibitor rapamycin had little effect on carbachol-stimulated eIF4B phosphorylation, suggesting that PI3K and mTORC1 are not the key participants in this process. We also observed that the inhibition of protein kinase C (PKC) by GF109203X greatly diminished carbachol-stimulated eIF4B phosphorylation. Together, our data show that mAChRs modulate eIF4B phosphorylation via the ERK1/2 and PKC signaling pathways in SNU-407 colon cancer cells. Highlights <UL> <LI> Muscarinic acetylcholine receptors (mAChRs) mediate eIF4B phosphorylation. </LI> <LI> The ERK1/2 signaling pathway is required for mAChR-mediated eIF4B phosphorylation. </LI> <LI> The PI3K-mTORC1 pathway is not important for mAChR-mediated eIF4B phosphorylation. </LI> <LI> Protein kinase C is involved in mAChR-mediated eIF4B phosphorylation. </LI> </UL>
2
아마인 추출물의 AKT 신호 조절을 통한 콕사키바이러스 증식억제

신하현,문성진,임병관,김진희 한국생약학회 2018 생약학회지 Vol.49 No.4
- 원문보기 2
  ScienceON
  
  DBpia
Coxsackievirus B3 (CVB3) is a very well-known causative agent for viral myocarditis and meningitis in human. However, the effective vaccine and therapeutic drug are not developed yet. CVB3 infection activates host cell AKT signaling. Inhibition of AKT signaling pathway may attenuate CVB3 replication and prevent CVB3-mediate viral myocarditis. In this study, we determined antiviral effect of the selected natural plant extract to develop a therapeutic drug for CVB3 treatment. We screened several chemically extracted natural compounds by using HeLa cell-based cell survival assay. Among them, Linum usitatissimum L. extract was selected for antiviral drug candidate. L. usitatissimum extract significantly decreased CVB3 replication and cell death in CVB3 infected HeLa cells with no cytotoxicity. CVB3 protease 2A induced eIF4G1 cleavage and viral capsid protein VP1 production were dramatically decreased by L. usitatissimum extract treatment. In addition, virus positive and negative strand genome amplification were significantly decreased by 1 mg/ml L. usitatissimum extract treatment. Especially, L. usitatissimum extract was associated with inhibition of AKT signal and maintain mTOR activity. In contrast, Atg12 and LC3 expression were not changed by L. usitatissimum extract treatment. In this study, the potential AKT signal inhibitor, L. usitatissimum extract, was significantly inhibited viral genome replication and protein production by inhibition of AKT signal. These results suggested that L. usitatissimum extract is a novel therapeutic agent for treatment of CVB3-mediated diseases.