105 research outputs found
Interferon-alpha-induced mTOR activation is an anti-hepatitis C virus signal via the phosphatidylinositol 3-kinase-Akt-independent pathway.
OBJECT: The interferon-induced Jak-STAT signal alone is not sufficient to explain all the biological effects of IFN. The PI3-K pathways have emerged as a critical additional component of IFN-induced signaling. This study attempted to clarify that relationship between IFN-induced PI3-K-Akt-mTOR activity and anti-viral action. RESULT: When the human normal hepatocyte derived cell line was treated with rapamycin (rapa) before accretion of IFN-alpha, tyrosine phosphorylation of STAT-1 was diminished. Pretreatment of rapa had an inhibitory effect on the IFN-alpha-induced expression of PKR and p48 in a dose dependent manner. Rapa inhibited the IFN-alpha inducible IFN-stimulated regulatory element luciferase activity in a dose-dependent manner. However, wortmannin, LY294002 and Akt inhibitor did not influence IFN-alpha inducible luciferase activity. To examine the effect of PI3-K-Akt-mTOR on the anti-HCV action of IFN-alpha, the full-length HCV replication system, OR6 cells were used. The pretreatment of rapa attenuated its anti-HCV replication effect in comparison to IFN-alpha alone, whereas the pretreatment with PI3-K inhibitors, wortmannin and LY294002 and Akt inhibitor did not influence IFN-induced anti-HCV replication. CONCLUSION: IFN-induced mTOR activity, independent of PI3K and Akt, is the critical factor for its anti-HCV activity. Jak independent mTOR activity involved STAT-1 phosphorylation and nuclear location, and then PKR is expressed in hepatocytes
Experimental and Theoretical Mechanistic Investigation of the Iridium-Catalyzed Dehydrogenative Decarbonylation of Primary Alcohols
Phosphines having a 2,3,4,5-tetraphenylphenyl moiety: Effective ligands in palladium-catalyzed transformations of aryl chlorides
Nickel-Catalyzed Acylstannylation of 1,3-Dienes: Synthesis and Reaction of Δ-Oxoallylstannanes
Rhodium(I) complexes with N-heterocyclic carbenes bearing a 2,3,4,5-tetraphenylphenyl and its higher dendritic frameworks
A bowl-shaped phosphine as a ligand in palladium-catalyzed Suzuki-Miyaura coupling of aryl chlorides: Effect of the depth of the bowl
Transition-Metal Complexes with Nano-Sized Phosphine and Pyridine Ligands-Catalysis, Fluxional Behavior and Molecular Recognition
Microvascular coupler device versus handâsewn venous anastomosis: A systematic review of the literature and data metaâanalysis
Venous Repair with Vascular Clips and Conventional Suture: A Comparative Experimental Study
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