The {beta}4 subunit of Cav1.2 channels is required for an optimal interferon response in cardiac muscle cells

The auxiliary β4 subunit of the cardiac Cav1.2 channel plays a poorly understood role in gene transcription. Here, we characterized the regulatory effects of the β4 subunit in H9c2 rat cardiac cells on the abundances of Ifnb mRNA [which encodes interferon-β (IFN-β)] and of the IFN-β–related genes Ddx58, Ifitm3, Irf7, Stat2, Ifih1, and Mx1, as well as on the abundances of the antiviral proteins DDX58, IRF7, STAT2, and IFITM3. Knocking down the β4 subunit in H9c2 cells reduced the expression of IFN-β–stimulated genes. In response to inhibition of the kinase JAK1, the abundances of β4 subunit mRNA and protein were decreased. β4 subunit abundance was increased, and it translocated to the nucleus, in cells treated with IFN-β, infected with dengue virus (DENV), or transfected with poly(I:C), a synthetic analog of double-stranded RNA. Cells that surrounded the virus-infected cells showed translocation of β4 subunit proteins to nuclei in response to spreading infection. We showed that the β4 subunit interacted with the transcriptional regulator IRF7 and that the activity of an Irf7 promoter–driven reporter was increased in cells overexpressing the β4 subunit. Last, overexpressing β4 in undifferentiated and differentiated H9c2 cells reduced DENV infection and decreased the abundance of the viral proteins NS1, NS3, and E-protein. DENV infection and poly(I:C) also increased the concentration of intra...
Source: Signal Transduction Knowledge Environment - Category: Science Authors: Tags: STKE Research Articles Source Type: news

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Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
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Source: Cell Host and Microbe - Category: Microbiology Authors: Tags: Cell Host Microbe Source Type: research
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Source: Viruses - Category: Virology Authors: Tags: Communication Source Type: research
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Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research
CONCLUSIONS: Our results suggest that severe stress alters molecules implicated in the development of leukopoietic stem cells, thereby leading to depletion of cellular and molecular repertoires of protective immunity. Suppressed molecules mediating membrane trafficking of recycling endosomes, membrane translocation and localization of the antigen processing mechanisms and cell adhesions indicate suboptimal antigen presentation, impaired formation of productive immunological synapses, and inhibited T-cell activations. These factors may collectively be responsible for compromised protective immunity (infection susceptibility...
Source: Brain, Behavior, and Immunity - Category: Neurology Authors: Tags: Brain Behav Immun Source Type: research
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Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
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Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
The β4 subunit of Cav1.2 channels is required for an optimal interferon response in cardiac muscle cells. Sci Signal. 2018 Dec 11;11(560): Authors: Tammineni ER, Carrillo ED, Soto-Acosta R, Angel-Ambrocio AH, García MC, Bautista-Carbajal P, Del Angel RM, Sánchez JA Abstract The auxiliary β4 subunit of the cardiac Cav1.2 channel plays a poorly understood role in gene transcription. Here, we characterized the regulatory effects of the β4 subunit in H9c2 rat cardiac cells on the abundances of Ifnb mRNA [which encodes interferon-β (IFN-β)] and of the IFN-β-relat...
Source: Science Signaling - Category: Biomedical Science Authors: Tags: Sci Signal Source Type: research
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Source: Prostaglandins and Other Lipid Mediators - Category: Lipidology Source Type: research
Publication date: Available online 4 May 2018 Source:Prostaglandins & Other Lipid Mediators Author(s): M.G. Anupriya, Sneha Singh, Neha Vijay Hulyalkar, Easwaran Sreekumar Dengue has emerged as a major mosquito-borne disease in the tropics and subtropics. In severe dengue, enhanced microvascular endothelial permeability leads to plasma leakage. Direct dengue virus (DENV) infection in human microvascular endothelial cells (HMEC-1) can enhance trans-endothelial leakage. Using a microarray-based analysis, we identified modulation of key endothelial cell signaling pathways in DENV-infected HMEC-1 cells. One among them was...
Source: Prostaglandins and Other Lipid Mediators - Category: Lipidology Source Type: research
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