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https://www.readbyqxmd.com/read/28724761/isg15-modulates-type-i-interferon-signaling-and-antiviral-response-during-hepatitis-e-virus-replication
#1
Harini Sooryanarain, Adam J Rogers, Dianjun Cao, Mary Etna R Haac, Yogesh A Karpe, Xiang-Jin Meng
Hepatitis E virus (HEV), a single-stranded positive-sense RNA virus, generally causes a self-limiting acute viral hepatitis, although chronic HEV infection has recently become a significant clinical problem in immunocompromised individuals especially in solid organ transplant recipients. Innate immunity, via type-I interferon (IFN) response, plays an important role during initial stages of a viral infection. ISG15, an IFN-induced ubiquitin-like protein, is known to have an immunomodulatory role, as well as can impart a direct antiviral effect against a wide spectrum of virus families...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724458/clinical-and-therapeutic-potential-of-protein-kinase-pkr-in-cancer-and-metabolism
#2
M B Garcia-Ortega, G J Lopez, G Jimenez, J A Garcia-Garcia, V Conde, H Boulaiz, E Carrillo, M Perán, J A Marchal, M A Garcia
The protein kinase R (PKR, also called EIF2AK2) is an interferon-inducible double-stranded RNA protein kinase with multiple effects on cells that plays an active part in the cellular response to numerous types of stress. PKR has been extensively studied and documented for its relevance as an antiviral agent and a cell growth regulator. Recently, the role of PKR related to metabolism, inflammatory processes, cancer and neurodegenerative diseases has gained interest. In this review, we summarise and discuss the involvement of PKR in several cancer signalling pathways and the dual role that this kinase plays in cancer disease...
July 20, 2017: Expert Reviews in Molecular Medicine
https://www.readbyqxmd.com/read/28703114/inhibition-of-perk-dependent-pro-adaptive-signaling-pathway-as-a-promising-approach-for-cancer-treatment
#3
Wioletta Rozpędek, Dariusz Pytel, Łukasz Dziki, Alicja Nowak, Adam Dziki, J Alan Diehl, Ireneusz Majsterek
Endoplasmic Reticulum (ER) is an organelle that is vital for cell growth and maintenance of homeostasis. Recent studies have reported that numerous human diseases, including cancer, are strictly connected to disruption of ER homeostasis. In order to counteract adverse intracellular conditions, cancer cells induce protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)-dependent, pro-adaptive unfolded protein response (UPR) signaling branches. If ER stress is severe or prolonged, pro-adaptive signaling networks are insufficient, resulting in apoptotic cell death of cancer cells...
June 30, 2017: Polski Przeglad Chirurgiczny
https://www.readbyqxmd.com/read/28702377/dsrna-binding-domain-of-pkr-is-proteolytically-released-by-enterovirus-a71-to-facilitate-viral-replication
#4
Yu-Hsiu Chang, Kean Seng Lau, Rei-Lin Kuo, Jim-Tong Horng
Enterovirus 71 (EV-A71) causes hand, foot and mouth disease in young children and infants, but can also cause severe neurological complications or even death. The double-stranded RNA (dsRNA)-dependent protein kinase R (PKR), an interferon-induced antiviral protein, phosphorylates the regulatory α-subunit of the eukaryotic translation initiation factor 2 in response to viral infection, thereby blocking the translation of cellular and viral mRNA and promoting apoptosis. The cleavage of PKR after infection with poliovirus, a prototype enterovirus, has been reported by others, but the underlying mechanism of this cleavage and its role in viral replication remain unclear...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28688954/rifampicin-induced-injury-in-hepg2-cells-is-alleviated-by-tudca-via-increasing-bile-acid-transporters-expression-and-enhancing-the-nrf2-mediated-adaptive-response
#5
Weiping Zhang, Lihong Chen, Hui Feng, Wei Wang, Yi Cai, Fen Qi, Xiaofang Tao, Jun Liu, Yujun Shen, Xiaofei Ren, Xi Chen, Jianming Xu, Yuxian Shen
Bile acid transporters and the nuclear factor erythroid 2-related factor (Nrf-2)-mediated adaptive response play important roles in the development of drug-induced liver injury (DILI). However, little is known about the contribution of the adaptive response to rifampicin (RFP)-induced cell injury. In this study, we found RFP decreased the survival rate of HepG2 cells and increased the levels of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), γ-glutamyl-transferase (γ-GT), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total bile acid (TBA) and adenosine triphosphate (ATP) in the cell culture supernatants in both a concentration- and a time-dependent manner...
July 6, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28688763/protective-function-of-slc30a10-induced-via-perk-atf4-pathway-against-1-methyl-4-phenylpyridinium
#6
Suzuna Go, Hisaka Kurita, Kazuki Yokoo, Masatoshi Inden, Taiho Kambe, Isao Hozumi
Solute carrier family 30 member 10 (SLC30A10) has been known as manganese transporter. It has been suggested that neurodegenerative diseases are related with cellular stress such as oxidative stress or endoplasmic reticulum (ER) stress. However, it remains unknown whether SLC30A10 is actually involved in several intracellular stress. We found that the level of Slc30a10 was increased in midbrain of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Therefore, we further investigated the role of SLC30A10 in the 1-methyl-4-phenylpiridium ion (MPP(+))-induced intracellular stress, and the molecular mechanism underlying SLC30A10 induction by MPP(+) treatment...
July 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28683312/an-ancient-pseudoknot-in-tnf-%C3%AE-pre-mrna-activates-pkr-inducing-eif2%C3%AE-phosphorylation-that-potently-enhances-splicing
#7
Lise Sarah Namer, Farhat Osman, Yona Banai, Benoît Masquida, Rodrigo Jung, Raymond Kaempfer
Tumor necrosis factor alpha (TNF-α) is expressed promptly during inflammatory responses. Efficient TNF-α mRNA splicing is achieved through a 3' UTR element that activates RNA-dependent eIF2α protein kinase (PKR). The TNF-α RNA activator, we show, folds into a pseudoknot conserved from teleost fish to humans, critical for PKR activation and mRNA splicing. The pseudoknot constrains the RNA into two double-helical stacks having parallel axes, permitting facile PKR dimerization and trans-autophosphorylation needed for kinase activation...
July 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28673044/ctenopharyngodon-idella-ikk%C3%AE-interacts-with-pkr-and-i%C3%AE%C2%BAb%C3%AE
#8
Haizhou Wang, Qun Xu, Xiaowen Xu, Yousheng Hu, Qunhao Hou, Youlin Zhu, Chengyu Hu
Inhibitor of nuclear factor kappa-B kinase β (IKKβ) is a subunit of the IKK complex. It can activate the NF-κB pathway through phosphorylating IκB in response to a wide range of stimuli. In the present study, an IKKβ gene from grass carp (Ctenopharyngodon idella; KT282114) was cloned and identified by homologous cloning and rapid-amplification of cDNA ends (RACE) technique. The complete CiIKKβ cDNA is 3428 bp in length, with the longest open reading frame (ORF) of 2337 bp encoding a polypeptide of 778 amino acids...
June 29, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28665481/the-pkr-regulatory-subunit-of-pka-is-involved-in-regulating-growth-sexual-and-asexual-development-and-pathogenesis-in-fusarium-graminearum
#9
Chaoqun Li, Yonghui Zhang, Huan Wang, Lingfeng Chen, Ju Zhang, Manli Sun, Jin-Rong Xu, Chenfang Wang
Fusarium graminearum is a causal agent of the wheat scab disease and a producer of deoxynivalenol (DON) mycotoxins. Treatment with exogenous cAMP increased its DON production. To better understand the role of the cAMP-PKA pathway in F. graminearum, in this study we functionally characterized the PKR gene encoding the regulatory subunit of PKA. Mutants deleted of PKR were viable but had severe defects in growth, conidiation, and plant infection. The pkr mutant produced compact colonies with shorter aerial hyphae that were increased in the number of nuclei in hyphal compartments...
June 30, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28662438/foot-and-mouth-disease-virus-induces-lysosomal-degradation-of-host-protein-kinase-pkr-by-3c-proteinase-to-facilitate-virus-replication
#10
Chuntian Li, Zixiang Zhu, Xiaoli Du, Weijun Cao, Fan Yang, Xiangle Zhang, Huanhuan Feng, Dan Li, Keshan Zhang, Xiangtao Liu, Haixue Zheng
The interferon-induced double-strand RNA activated protein kinase (PKR) plays important roles in host defense against viral infection. Here we demonstrate the significant antiviral role of PKR against foot-and-mouth disease virus (FMDV) and report that FMDV infection inhibits PKR expression and activation in porcine kidney (PK-15) cells. The viral nonstructural protein 3C proteinase (3C(pro)) is identified to be responsible for this inhibition. However, it is independent of the well-known proteinase activity of 3C(pro) or 3C(pro)-induced shutoff of host protein synthesis...
September 2017: Virology
https://www.readbyqxmd.com/read/28648883/molecular-cloning-and-functional-analysis-of-tumor-necrosis-factor-receptor-associated-factor-6-traf6-in-crossastrea-gigas
#11
Fan Mao, Jun Li, Yuehuan Zhang, Zhiming Xiang, Yang Zhang, Ziniu Yu
Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been demonstrated to be a key signaling molecule involved in adaptive and innate immunity. In this study, we obtained the full length CgTRAF6 cDNA and analyzed the characteristics of the ORF and the peptide sequence in Crassostrea gigas. The deduced protein sequence of CgTRAF6 includes a conserved C-terminal TRAF domain following the RING and the zinc finger domain. The TRAF domain is composed of coiled-coil TRAF-N and MATH (meprin and TRAF-C homology) subdomains...
June 23, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28628858/unravelling-the-structural-interactions-between-pkr-kinase-domain-and-its-small-molecule-inhibitors-using-computational-approaches
#12
Sagar Barage, Abhijeet Kulkarni, Jayanta K Pal, Manali Joshi
The RNA-dependent protein kinase (PKR), an eIF2α kinase plays an important role in anti-viral response, apoptosis and cell survival. It is also implicated to play a role in several cancers, metabolic and neurodegenerative disorders. A few ATP competitive inhibitors of the PKR have been reported in the literature with promising results in vitro and in vivo. The aim of this study was to unravel the structural interactions between these inhibitors and the PKR kinase domain using molecular simulations and docking...
June 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28628829/ectromelia-virus-accumulates-less-double-stranded-rna-compared-to-vaccinia-virus-in-bs-c-1-cells
#13
Tiffany R Frey, Michael H Lehmann, Colton M Ryan, Marie C Pizzorno, Gerd Sutter, Adam R Hersperger
Most orthopoxviruses, including vaccinia virus (VACV), contain genes in the E3L and K3L families. The protein products of these genes have been shown to combat PKR, a host defense pathway. Interestingly, ectromelia virus (ECTV) contains an E3L ortholog but does not possess an intact K3L gene. Here, we gained insight into how ECTV can still efficiently evade PKR despite lacking K3L. Relative to VACV, we found that ECTV-infected BS-C-1 cells accumulated considerably less double-stranded (ds) RNA, which was due to lower mRNA levels and less transcriptional read-through of some genes by ECTV...
September 2017: Virology
https://www.readbyqxmd.com/read/28624282/effect-of-endoplasmic-reticulum-stress-on-metabolic-and-stress-signaling-and-kidney-specific-functions-in-madin-darby-bovine-kidney-cells
#14
E Chiappisi, R Ringseis, K Eder, D K Gessner
Recent studies demonstrated induction of endoplasmic reticulum (ER) stress in tissues of cows after parturition, but knowledge about the effect of ER stress on important cellular processes, such as critical signaling and metabolic pathways, in cattle is scarce. Thus, the present study aimed to investigate the effect of ER stress induction on nuclear factor-κB (NF-κB), nuclear factor E2-related factor 2 (Nrf2), and sterol regulatory element-binding protein (SREBF1) pathway in Madin-Darby bovine kidney (MDBK) cells, a widely used in vitro model in ruminant research...
June 14, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28623239/-ccug-n-rna-toxicity-in-a-drosophila-model-for-myotonic-dystrophy-type-2-dm2-activates-apoptosis
#15
Vildan Betul Yenigun, Mario Sirito, Alla Amcheslavky, Tomek Czernuszewicz, Jordi Colonques-Bellmunt, Irma García-Alcover, Marzena Wojciechowska, Clare Bolduc, Zhihong Chen, Arturo López Castel, Ralf Krahe, Andreas Bergmann
The myotonic dystrophies are prototypic toxic RNA gain-of-function diseases. Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are caused by different unstable, noncoding microsatellite repeat expansions -- (CTG)DM1 in DMPK and (CCTG)DM2 in CNBP Although transcription of mutant repeats into (CUG)DM1 or (CCUG)DM2 appears to be necessary and sufficient to cause disease, their pathomechanisms remain incompletely understood. To study the mechanisms of (CCUG)DM2 toxicity and develop a convenient model for drug screening, we generated a transgenic DM2 model in the fruit fly Drosophila melanogaster with (CCUG)n repeats of variable length (n=16 and 106)...
June 16, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28615521/ier3ip1-deficiency-leads-to-increased-%C3%AE-cell-death-and-decreased-%C3%AE-cell-proliferation
#16
Juan Sun, Decheng Ren
Mutations in the gene for Immediate Early Response 3 Interacting Protein 1 (IER3IP1) cause permanent neonatal diabetes mellitus in human. The mechanisms involved have not been determined and the role of IER3IP1 in β-cell survival has not been characterized. In order to determine if there is a molecular link between IER3IP1 deficiency and β-cell survival and proliferation, we knocked down Ier3ip1 gene expression in mouse MIN6 insulinoma cells. IER3IP1 suppression induced apoptotic cell death which was associated with an increase in Bim and a decrease in Bcl-xL...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611419/interaction-of-pkr-with-single-stranded-rna
#17
Christopher B Mayo, James L Cole
Although the antiviral kinase PKR was originally characterized as a double-stranded RNA activated enzyme it can be stimulated by RNAs containing limited secondary structure. Single-stranded regions in such RNAs contribute to binding and activation but the mechanism is not understood. Here, we demonstrate that single-stranded RNAs bind to PKR with micromolar dissociation constants and can induce activation. Addition of a 5'-triphosphate slightly enhances binding affinity. Single-stranded RNAs also activate PKR constructs lacking the double-stranded RNA binding domain and bind to a basic region adjacent to the N-terminus of the kinase...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28602740/protective-immunity-against-rock-bream-iridovirus-rbiv-infection-and-tlr3-mediated-type-i-interferon-signaling-pathway-in-rock-bream-oplegnathus-fasciatus-following-poly-i-c-administration
#18
Myung-Hwa Jung, Sung-Ju Jung
In this study, we evaluated the potential of poly (I:C) to induce antiviral status for protecting rock bream from RBIV infection. Rock bream injected with poly (I:C) at 2 days before infection (1.1 × 10(4)) at 20 °C had significantly higher protection with RPS 13.4% and 33.4% at 100 and 200 μg/fish, respectively, through 100 days post infection (dpi). The addition of boost immunization with poly (I:C) at before/post infection at 20 °C clearly enhanced the level of protection showing 33.4% and 60.0% at 100 and 200 μg/fish, respectively...
August 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28601430/imiquimod-induced-autophagy-is-regulated-by-er-stress-mediated-pkr-activation-in-cancer-cells
#19
Shu-Hao Chang, Shi-Wei Huang, Sin-Ting Wang, Kai-Cheng Chung, Chia-Wei Hsieh, Jun-Kai Kao, Yi-Ju Chen, Chun-Ying Wu, Jeng-Jer Shieh
BACKGROUND: Autophagy is a highly conserved cellular catabolic pathway for degradation and recycling of intracellular components in response to nutrient starvation or environmental stress. Endoplasmic reticulum (ER) homeostasis can be disturbed by physiological and pathological influences, resulting in accumulation of misfolded and unfolded proteins in the ER lumen, a condition referred to as ER stress. Imiquimod (IMQ), a Toll-like receptor (TLR) 7 ligand, possesses anti-tumor and anti-viral activities in vitro and in vivo...
May 2, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28592527/zika-virus-hijacks-stress-granule-proteins-and-modulates-the-host-stress-response
#20
Shangmei Hou, Anil Kumar, Zaikun Xu, Adriana M Airo, Iryna Stryapunina, Cheung Pang Wong, William Branton, Egor Tchesnokov, Matthias Götte, Christopher Power, Tom C Hobman
Zika virus (ZIKV), a member of the Flaviviridae family, has recently emerged as an important human pathogen with increasing economic and health impact worldwide. Because of its teratogenic nature and association with the serious neurological condition Guillain-Barré syndrome, a tremendous amount of effort has focused on understanding ZIKV pathogenesis. To gain further insights into ZIKV interaction with host cells, we investigated how this pathogen affects stress response pathways. While ZIKV infection induces stress signaling that leads to phosphorylation of eIF2α and cellular translational arrest, stress granule (SG) formation was inhibited...
June 7, 2017: Journal of Virology
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