- |||||||||| Journal: AICAR enhances the cytotoxicity of PFKFB3 inhibitor in an AMPK signaling-independent manner in colorectal cancer cells. (Pubmed Central) - Mar 1, 2022
Moreover, it failed to enhance PFK-15's cytotoxicity in the AKT1/2-silenced cells, indicating AKT-mTORC1 participated during these processes. Collectively, the presented data demonstrated that PFK-15 inhibited cell viability, AMPK, and AKT-mTORC1 signaling, and AICAR probably enhanced the cell viability loss aroused by PFK-15 in an AKT-dependent and AMPK-independent manner, thereby revealing a more intimate relationship among PFKFB3, AMPK, and AKT-mTORC1 signaling pathways.
- |||||||||| dorsomorphin (Compound C) / EMD Serono
Journal: Icariin inhibits isoproterenol-induced cardiomyocyte hypertropic injury through activating autophagy via the AMPK/mTOR signaling pathway. (Pubmed Central) - Mar 1, 2022 Mechanistically, ICA increased the phosphorylation levels of AMPK and autophagy-related markers beclin-1, Atg5 and the LC3II/I ratio, and decreased phosphorylated mTOR. But the effects of ICA on ISO-induced cardiomyocytes hypertrophy were attenuated by selective AMPK inhibitor Compound C. In conclusion, these findings indicated that ICA attenuated cardiomyocyte hypertrophy induced by ISO and prevented cell injury, and the specific mechanism was mediated by AMPK/mTOR pathway to enhance autophagy and reduce autophagy-related cardiomyocyte apoptosis.
- |||||||||| luminespib (AUY922) / Ligand
Journal: NVP-AUY922 alleviates radiation-induced lung injury via inhibition of autophagy-dependent ferroptosis. (Pubmed Central) - Mar 1, 2022 Mechanistically, NVP-AUY922 prevented chaperone-mediated autophagy of the GPX4 pathway in vitro and in vivo, and the autophagy inhibitor Baf-A1 significantly increased the level of GPX4 and alleviated lung inflammation. NVP-AUY922 can alleviate RILI by inhibiting chaperone-mediated lysosomal degradation of GPX4, demonstrating its potential as a novel protective agent against RILI.
- |||||||||| Journal: Vitamin D3 promotes autophagy in THP-1 cells infected with Mycobacterium tuberculosis. (Pubmed Central) - Mar 1, 2022
In conclusion, the present study indicated that vitamin D3 may activate cell autophagy signals by inhibiting the concentration of Ca. These data may improve understanding of the effect of vitamin D3 on M.tb infection and help determine the underlying mechanism of vitamin D3 to alleviate and treat the inflammatory response caused by TB.
- |||||||||| sirolimus / Generic mfg.
Journal: ATGL deficiency aggravates pressure overload-triggered myocardial hypertrophic remodeling associated with the proteasome-PTEN-mTOR-autophagy pathway. (Pubmed Central) - Feb 27, 2022 Interestingly, ATGL KO-mediated cardiac dysfunction and remodeling were markedly reversed by proteasome inhibitor (epoxomicin) or autophagic activator (rapamycin), but accelerated by PTEN inhibitor (VO-OHpic) or autophagy inhibitor 3-MA...TAC-induced downregulation of ATGL results in increased proteasome (β1i/β2i/β5i) activity, which in turn promotes degradation of PTEN and activation of AKT-mTOR signaling and then inhibits autophagy and ATP production, thereby leading to cardiac hypertrophic remodeling and dysfunction. Conversely, blocking proteasome activity or activating autophagy attenuates these effects.
- |||||||||| temozolomide / Generic mfg.
Clinical, Review, Journal: Autophagy inhibition is the next step in the treatment of glioblastoma patients following the Stupp era. (Pubmed Central) - Feb 26, 2022 Promising results have been observed in patients with glioma for over a decade now when autophagy inhibition with chloroquine derivatives coupled with conventional therapy. The application of autophagy inhibitors, the role of immune cell-induced autophagy, and the potential role of novel cellular and gene therapies, should now be considered for development as part of this well-established regimen.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: NRF2 Activation in Autophagy Defects Suppresses a Pharmacological Transactivation of the Nuclear Receptor FXR. (Pubmed Central) - Feb 26, 2022 Obeticholic acid as a potent FXR agonist has been approved to treat primary biliary cholangitis and clinical trials for its use in the treatment of other liver diseases are underway...Finally, we demonstrate that NRF2 activation by the treatment with the food antioxidant butylated hydroxyanisole is necessary and sufficient to inhibit the pharmacological activation of FXR in vivo. These results reveal a novel function of the basal autophagy-NRF2 axis for the regulation of FXR transactivation, and shed light on a potential therapeutic strategy in metabolic disease.
- |||||||||| sirolimus / Generic mfg.
Journal: Fisetin Inhibits Autophagy in HepG2 Cells via PI3K/Akt/mTOR and AMPK Pathway. (Pubmed Central) - Feb 25, 2022 Taken together, the results revealed that fisetin inhibited autophagy by the activation of PI3K/Akt/mTOR and modulation of AMPK signaling pathways. Our findings indicate that suppression of autophagy by fisetin may serve as an effective therapeutic strategy against HCC.
- |||||||||| Review, Journal: AMPK: a key regulator of energy stress and calcium-induced autophagy. (Pubmed Central) - Feb 25, 2022
However, the physiological significance of the regulation of autophagy by cytoplasmic calcium is currently unclear. This review focuses on the current understanding of the mechanism of autophagy and its regulation by AMPK.
- |||||||||| GYY4137 / National University of Singapore
Journal: AMPK S-sulfuration contributes to HS donors-induced AMPK phosphorylation and autophagy activation in dopaminergic cells. (Pubmed Central) - Feb 24, 2022 In this study we reported that exogenous HS donors NaHS and GYY4137 (GYY) enhanced the autophagy activity, as indicated by the increases of autophagy marker LC3-II expression and LC3 dots formation even during lysosome inhibition in dopaminergic cell lines and HEK293 cells...Further, NaHS was able to attenuate α-synuclein accumulation in a cellular model induced by dopamine oxidized metabolite 3, 4-dihydroxyphenylacetaldehyde (DOPAL), and this effect was interfered by autophagy inhibitor wortmannin and also eliminated in AMPK Cys302A-transfected cells. In sum, the findings identified a role of Cys302 S-sulfuration in AMPK activation induced by exogenous HS and demonstrated that HS donors could enhance the autophagic flux via AMPK-mTOR signaling and thus reduce α-synuclein accumulation in vitro.
- |||||||||| cisplatin / Generic mfg.
Journal, Cancer stem cells: Autophagy regulates the cancer stem cell phenotype of head and neck squamous cell carcinoma through the noncanonical FOXO3/SOX2 axis. (Pubmed Central) - Feb 24, 2022 Pretreatment with autophagy inhibitors, such as 3-MA and chloroquine, diminished the CSC properties acquired under adverse conditions...Taken together, our findings suggest that the activation of autophagy is essential for the acquisition of CSC properties in adverse conditions and the self-renewal of CSCs. We clarify the role of autophagy in regulating the CSC phenotype and demonstrate that the noncanonical FOXO3/SOX2 axis is the intrinsic regulatory mechanism.
- |||||||||| sirolimus / Generic mfg.
Biomarker, Journal: Robust LC3B lipidation analysis by precisely adjusting autophagic flux. (Pubmed Central) - Feb 24, 2022 Significant autophagic flux increase by rapamycin could only be observed when combining it with BafA concentrations not affecting basal flux, a condition which created a bottleneck, rather than fully blocking autophagosome-lysosome fusion, concomitant with autophagy stimulation...To demonstrate the validity of this approach, we show that a novel inhibitor of the acetyltransferase EP300 activates autophagy in a mTORC1-dependent manner. We propose that the creation of a sensitized background rather than a full block of autophagosome progression is required to quantitatively capture changes in autophagic flux.
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