scholarly journals Integrated Stress Response Signaling Pathways Induced by Supraphysiological Concentrations of Thyroid Hormone Inhibit Viral Replication

2016 ◽  
Vol 5 ◽  
pp. STI.S39844 ◽  
Author(s):  
Mohammad Ishaq ◽  
Ven Natarajan
Keyword(s):  
Stress Response ◽  
Signaling Pathways ◽  
Antiviral Agents ◽  
Integrated Stress Response ◽  
Dependent Protein Kinase ◽  
Antiviral Responses ◽  
Stress Markers ◽  
Signaling Mechanisms ◽  
Dependent Protein ◽  
Vesicular Stomatitis

Supraphysiological concentrations (SPCs) of triiodo-L-thyronine (T3) have been used in the treatment of a number of nonviral diseases. However, the signaling mechanisms that regulate the function of T3 at these concentrations and their role in modulating cellular stress pathways and antiviral responses are unknown. Here, we have investigated the effects of SPCs of T3 on integrated stress response (ISR) signaling pathways and the replication of vesicular stomatitis virus (VSV). T3 amplified Poly IC-induced activation of RNA-dependent protein kinase, induced phosphorylation of eIF2α, stress granule (SG) formation, IRE1α phosphorylation, XBP1 splicing, and the expression of stress markers. T3 inhibited VSV replication by modulating SG formation and the expression of stress response markers. ISR activator guanabenz also inhibited VSV replication and amplified T3-induced anti-VSV response. To summarize, we have uncovered novel functions of T3 at SPCs as an activator of ISR signaling pathways and an inhibitor of VSV replication. This study offers a proof of principle of the concept that ISR activating agents like SPC of T3 and guanabenz can be potential antiviral agents.

scholarly journals Dishevelled activates Ca2+ flux, PKC, and CamKII in vertebrate embryos

2003 ◽  
Vol 161 (4) ◽  
pp. 769-777 ◽  
Author(s):  
Laird C. Sheldahl ◽  
Diane C. Slusarski ◽  
Petra Pandur ◽  
Jeffrey R. Miller ◽  
Michael Kühl ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Heart Development ◽  
Intracellular Signaling ◽  
Planar Cell Polarity ◽  
Intracellular Protein ◽  
Dependent Protein Kinase ◽  
Calcium Calmodulin Dependent ◽  
Wnt Ligands ◽  
Dependent Protein ◽  
Vertebrate Embryos

Wnt ligands and Frizzled (Fz) receptors have been shown to activate multiple intracellular signaling pathways. Activation of the Wnt–β-catenin pathway has been described in greatest detail, but it has been reported that Wnts and Fzs also activate vertebrate planar cell polarity (PCP) and Wnt–Ca2+ pathways. Although the intracellular protein Dishevelled (Dsh) plays a dual role in both the Wnt–β-catenin and the PCP pathways, its potential involvement in the Wnt–Ca2+ pathway has not been investigated. Here we show that a Dsh deletion construct, XDshΔDIX, which is sufficient for activation of the PCP pathway, is also sufficient for activation of three effectors of the Wnt–Ca2+ pathway: Ca2+ flux, PKC, and calcium/calmodulin-dependent protein kinase II (CamKII). Furthermore, we find that interfering with endogenous Dsh function reduces the activation of PKC by Xfz7 and interferes with normal heart development. These data suggest that the Wnt–Ca2+ pathway utilizes Dsh, thereby implicating Dsh as a component of all reported Fz signaling pathways.

scholarly journals The Tor and cAMP-dependent protein kinase signaling pathways coordinately control autophagy inSaccharomyces cerevisiae

Autophagy ◽  
2010 ◽  
Vol 6 (2) ◽  
pp. 294-295 ◽  
Author(s):  
Joseph S. Stephan ◽  
Yuh-Ying Yeh ◽  
Vidhya Vidhya Ramachandran ◽  
Stephen J. Deminoff ◽  
Paul K. Herman
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Kinase Signaling ◽  
Dependent Protein Kinase ◽  
Camp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Protein Kinase Signaling

5. Analysis of antiviral state in RD114 and A204 cells after interferon treatment

1982 ◽  
Vol 299 (1094) ◽  
pp. 135-137
Keyword(s):  
Encephalomyocarditis Virus ◽  
3T3 Cells ◽  
Dependent Protein Kinase ◽  
Clonal Cell Line ◽  
Antiviral State ◽  
Antiviral Effects ◽  
Dependent Protein ◽  
Antiviral Activities ◽  
Vesicular Stomatitis ◽  
Nih 3T3

Interferon exerts antiviral and various non-antiviral activities on cells. For the development of the antiviral state in cells against exogenous infection of cytolytic viruses such as vesicular stomatitis virus and encephalomyocarditis virus (EMCV), induction of 2'-5'-oligo(A) synthetase or double-stranded (ds)-RNA-dependent protein kinase, or both, has been shown to have a crucial role (Revel 1979). However, in some cases, the antiviral effects of interferon are virus-specific (Nilsen et al. 1980; Samuel & Knutson 1981). Recently, different effects of mouse interferon on retrovirus production and on EM CV replication in a clonal cell line from NIH / 3T3 cells were reported (Gzarniecki et al. 1981).

VEGF induces NO-dependent hyperpermeability in coronary venules

1996 ◽  
Vol 271 (6) ◽  
pp. H2735-H2739 ◽  
Author(s):  
H. M. Wu ◽  
Q. Huang ◽  
Y. Yuan ◽  
H. J. Granger
Keyword(s):  
Microvascular Permeability ◽  
Vascular Endothelial ◽  
Dependent Protein Kinase ◽  
Apparent Permeability ◽  
Signaling Mechanisms ◽  
Apparent Permeability Coefficient ◽  
Dependent Protein ◽  
Endothelial Growth Factor ◽  
Stimulation Of

The purpose of this study was to investigate the direct effect of vascular endothelial growth factor (VEGF) on microvascular permeability and its signaling mechanisms. The apparent permeability coefficient to albumin was measured in isolated coronary venules. Topical application of VEGF dose-dependently and transiently increased albumin permeability by two- to threefold. Inhibition of nitric oxide (NO) synthesis with NG-monomethyl-L-arginine abolished VEGF-induced venular hyperpermeability. Furthermore, because NO exerts vasoactive effects through stimulation of guanylate cyclase (GC) and the subsequent production of guanosine 3',5'-cyclic monophosphate (cGMP), we examined the role of GC and cGMP-dependent protein kinase (PKG) in the mediation of VEGF's action. The permeability response to VEGF was measured in the presence of the selective GC inhibitor 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one and the specific PKG inhibitor KT-5823. Both inhibitors reduced basal permeability and prevented the hyperpermeability response to VEGF. Therefore, we suggest that VEGF modulates microvascular permeability via a signaling cascade involving NO synthesis, GC stimulation, and PKG activation.

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