The involvement of HIF-1α reduction in quercetin-based cancer control was clearly shown in conditions of mTOR inhibition by rapamycin, an mTOR inhibitor. Surprisingly, quercetin induced an AMPK-suppressed state in a CoCl 2 -induced hypoxic condition. It is speculated that quercetin is capable of...
Additionally, hGECs was pretreated with LY294002 (PI3K signaling inhibitor) or Compound C (AMPK inhibitor) for 12 h and exposed them to Pg for 24 h. Subsequently, apoptosis was detected using flow cytometry, and expression and activity of Bcl-2, Bad, Bax, PI3K, AKT, AMPK, mTOR, and ...
Furthermore,autophagyispromotedbyAMPactivatedproteinkinase(AMPK),whichisakeyenergysensorandregulatescellular metabolismtomaintainenergyhomeostasis.Conversely,autophagyisinhibitedbythemammaliantargetofrapamycin(mTOR), acentralcell-growthregulatorthatintegratesgrowthfactorandnutrientsignals.Herewedemonstrateamolecularmechanism ...
The Akt/mTOR signaling pathway is activated in colon cancer. The well known mTOR inhibitor rapamycin has a disadvantage of feedback stimulation of Akt. Anthocyanins are naturally-occurring mTOR inhibitor possessing Akt inhibitory activities. We have investigated the mTOR inhibitory effect of anthocyanins...
mTORC1 与ULK1 复合体分离,使得ULK1 与mAtg13 抑制性磷酸化位点去磷酸化, ULK1 除发生自身磷酸化外,还可进一步磷酸化 FIP200 及 mAtg13 的激活性磷酸化位点,使得它 们再反馈激活ULK1,从而促进自噬的发生。 120 在哺乳动物中,AMPK 或 ULK1 的缺失会导致自噬特异性蛋白 p62 的异常积累以及缺 ...
The degree of injury to the myocardium/cells, oxidative stress, AMPK/mammalian target of rapamycin (mTOR) signaling and autophagy status were analyzed. In diabetic rats the myocardial infarct size, and creatine kinase‑MB and malondialdehyde release, were increased compared with non‑diabetic rats...
To determine whether activation of AMPK is truly responsible for iron chelation-induced mTORC1 inhibition, A549, A427, and Rh30 cells were pretreated with Compound C, an AMPK inhibitor, followed by CPX or Dp44mT treatment for 24 h. As expected, Compound C successfully inhibited iron chelation...
[29]. Here, salicylate activated AMPK, which was largely prevented by the AMPK inhibitor dorsomorphin (Fig.7A). Furthermore, the induction of NRF2 and NQO1, which is encoded by a NRF2 target gene, by salicylate was largely prevented by dorsomorphin (Fig.7A). Finally, the induction ofpri-...
作用通路:Epigenetics; PI3K/Akt/mTOR; TGF-beta/Smad; Autophagy; 体外研究: 在肝细胞中,Dorsomorphin通过AICAR或二甲双胍抑制ACC失活,并减弱AICAR或二甲双胍增加脂肪酸氧化或抑制脂肪生成基因的作用。HT-29细胞中,Dorsomorphin对AMPK活性的抑制几乎完全抑制自噬蛋白质水解。此外,Dorsomorphin选择性抑制BMPI型受体ALK2,...
而AMPK所起到的抑制脂肪合成以及促进脂肪分解等功能可以使这些疾病中的代谢从紊乱状态回归到正常稳态，特别是其同时通过抑制另一个促进合成代谢和细胞增殖的蛋白质mTOR的活性，能够缓解上述病征，甚至延年益寿。“辟谷精”正是通过模拟卡路里限制，造成类似于葡萄糖水平下降时的“假饥饿” ——即便在吃饱喝足状态下——...