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https://www.readbyqxmd.com/read/28070110/melatonin-suppresses-methamphetamine-triggered-endoplasmic-reticulum-stress-in-c6-cells-glioma-cell-lines
#1
Wanida Tungkum, Pichaya Jumnongprakhon, Chainarong Tocharus, Piyarat Govitrapong, Jiraporn Tocharus
Methamphetamine (METH) is a neurotoxic drug that causes brain damage by inducing neuronal and glial cell death together with glial cell hyperactivity-mediated progressive neurodegeneration. Previous studies have shown that METH induced glial cell hyperactivity and death via oxidative stress, the inflammatory response, and endoplasmic reticulum stress (ER stress) mechanisms, and melatonin could reverse these effects. However, the exact mechanism of the protective role of melatonin in METH-mediated ER stress has not been understood...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28069888/human-non-coding-rna-886-nc886-adopts-two-structurally-distinct-conformers-that-are-functionally-opposing-regulators-of-pkr
#2
Brenda M Calderon, Graeme L Conn
The double-stranded RNA (dsRNA)-activated protein kinase (PKR) senses dsRNA produced during viral infection and halts cellular protein synthesis to block viral replication. How basal PKR activity is controlled in the absence of infection was unclear until the recent identification of a potential endogenous regulator, the cellular non-coding RNA 886 (nc886). However, nc886 adopts two distinct conformations for which the structural details and potential functional differences remain unclear. Here, we isolated and separately dissected the function of form of nc886 to more clearly define the molecular mechanism of nc886-mediated PKR inhibition...
January 9, 2017: RNA
https://www.readbyqxmd.com/read/28069423/identification-and-characterization-of-pyrokinin-and-capa-peptides-and-corresponding-gpcrs-from-spotted-wing-drosophila-drosophila-suzukii
#3
Man-Yeon Choi, Seung-Joon Ahn, A Young Kim, Youngho Koh
The family of FXPRLamide peptides serves as a major insect hormone. It is characterized by a core active amino acid sequence conserved at the C-terminal ends, and provides various physiological roles across the Insecta. In this study we identified and characterized pyrokinin (PK) and Capa cDNAs encoding two FXPRLamide peptides, pyrokinin and CAPA-DH (diapause hormone), and two corresponding G-protein-coupled receptors (GPCRs) from spotted wing drosophila (SWD), Drosophila suzukii. Expressions of PK and CAPA mRNAs were differentially observed during all life stages except the embryo, and the detection of CAPA transcription was relatively strong compared with the PK gene in SWD...
January 6, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28062005/gga-mir-2127-downregulates-the-translation-of-chicken-p53-and-attenuates-chp53-mediated-innate-immune-response-against-ibdv-infection
#4
Wei Ouyang, Yong-Shan Wang, Kai Meng, Qun-Xing Pan, Xiao-Li Wang, Xing-Xia Xia, Yu-Mei Zhu, Zhen-Wei Bi, Hai-Bin Zhang, Kai Luo
Infectious bursal disease (IBD) is characterized by the immune suppression of infected birds. The molecular mechanism by which IBD virus (IBDV) suppresses the host immune system remains to be elucidated. The tumor suppressor protein p53 can inhibit the replication of various viruses, but its effect on IBDV remains unknown. This study established an in vitro infection model based on DF-1 cells (chicken embryo fibroblast cell line) to investigate the antiviral effects of chicken p53 (chp53) on IBDV infection...
January 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28061446/%C3%AE-40p53-is-involved-in-the-inactivation-of-autophagy-and-contributes-to-inhibition-of-cell-death-in-hct116-%C3%AE-40p53-cells
#5
Yunjin Zang, Ying Shi, Kai Liu, Luxin Qiao, Xianghua Guo, Dexi Chen
Δ40p53 is an isoform of wild-type p53 (wtp53). Here, we assessed whether Δ40p53 has the same functions as wild-type p53 in the regulation of cell death and autophagy. First, we used HCT116 (p53+/+) and H1299 (p53-free) cells to produce two cell lines (HCT116-Δ40p53 and H1299-Δ40p53) that express exogenous Δ40p53 but not wtp53. By using these cell lines, we determined that Δ40p53 inhibited starvation-induced autophagy, as does wtp53. This inhibition arises from both Δ40p53 and wtp53 having 3'-5' exonuclease activity, which reduces the levels of double-stranded RNA (dsRNA) and then inhibits PKR/eIF2α-induced autophagy in cells exposed to starvation...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28017918/effects-of-ketamine-administration-on-mtor-and-reticulum-stress-signaling-pathways-in-the-brain-after-the-infusion-of-rapamycin-into-prefrontal-cortex
#6
Helena M Abelaira, Gislaine Z Réus, Zuleide M Ignácio, Maria Augusta B Dos Santos, Airam B de Moura, Danyela Matos, Júlia P Demo, Júlia B I da Silva, Monique Michels, Mariane Abatti, Beatriz Sonai, Felipe Dal Pizzol, André F Carvalho, João Quevedo
Recent studies show that activation of the mTOR signaling pathway is required for the rapid antidepressant actions of glutamate N-methyl-D-aspartate (NMDA) receptor antagonists. A relationship between mTOR kinase and the endoplasmic reticulum (ER) stress pathway, also known as the unfolded protein response (UPR) has been shown. We evaluate the effects of ketamine administration on the mTOR signaling pathway and proteins of UPR in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens, after the inhibiton of mTOR signaling in the PFC...
December 3, 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28011649/newcastle-disease-virus-induces-stable-formation-of-bona-fide-stress-granules-to-facilitate-viral-replication-through-manipulating-host-protein-translation
#7
Yingjie Sun, Luna Dong, Shengqing Yu, Xiaoxu Wang, Hang Zheng, Pin Zhang, Chunchun Meng, Yuan Zhan, Lei Tan, Cuiping Song, Xusheng Qiu, Guijun Wang, Ying Liao, Chan Ding
Mammalian cells respond to various environmental stressors to form stress granules (SGs) by arresting cytoplasmic mRNA, protein translation element, and RNA binding proteins. Virus-induced SGs function in different ways, depending on the species of virus; however, the mechanism of SG regulation of virus replication is not well understood. In this study, Newcastle disease virus (NDV) triggered stable formation of bona fide SGs on HeLa cells through activating the protein kinase R (PKR)/eIF2α pathway. NDV-induced SGs contained classic SG markers T-cell internal antigen (TIA)-1, Ras GTPase-activating protein-binding protein (G3BP)-1, eukaryotic initiation factors, and small ribosomal subunit, which could be disassembled in the presence of cycloheximide...
December 23, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28008894/the-specific-protein-kinase-r-pkr-inhibitor-c16-protects-neonatal-hypoxia-ischemia-brain-damages-by-inhibiting-neuroinflammation-in-a-neonatal-rat-model
#8
Jinglei Xiao, Yongchang Tan, Yinjiao Li, Yan Luo
BACKGROUND Brain injuries induced by hypoxia-ischemia in neonates contribute to increased mortality and lifelong neurological dysfunction. The specific PKR inhibitor C16 has been previously demonstrated to exert a neuroprotective role in adult brain injuries. However, there is no recent study available concerning its protective role in hypoxia-ischemia-induced immature brain damage. Therefore, we investigated whether C16 protects against neonatal hypoxia-ischemia injuries in a neonatal rat model. MATERIAL AND METHODS Postnatal day 7 (P7) rats were used to establish classical hypoxia-ischemia animal models, and C16 postconditioning with 100 ug/kg was performed immediately after hypoxia...
December 23, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27994435/pkr-promotes-choroidal-neovascularization-via-upregulating-the-pi3k-akt-signaling-pathway-in-vegf-expression
#9
Manhui Zhu, Xiaojuan Liu, Shengcun Wang, Jin Miao, Liucheng Wu, Xiaowei Yang, Ying Wang, Lihua Kang, Wendie Li, Chen Cui, Hui Chen, Aimin Sang
PURPOSE: The aim of this study was to investigate the functions of dsRNA-activated protein kinase (PKR) in choroidal neovascularization (CNV) and related signaling pathways in the production of vascular endothelial growth factor (VEGF). METHODS: A chemical hypoxia model of in vitro RF/6A cells, a rhesus choroid-retinal endothelial cell line, was established by adding cobalt chloride (CoCl2) to the culture medium. PKR, phosphophosphatidylinositol 3-kinase (p-PI3K), phosphoprotein kinase B (p-Akt), and VEGF protein levels in RF/6A cells were detected with western blotting...
2016: Molecular Vision
https://www.readbyqxmd.com/read/27993242/hiv-protease-inhibitors-alter-amyloid-precursor-protein-processing-via-%C3%AE-site-amyloid-precursor-protein-cleaving-enzyme-1-translational-up-regulation
#10
Patrick J Gannon, Cagla Akay-Espinoza, Alan C Yee, Lisa A Briand, Michelle A Erickson, Benjamin B Gelman, Yan Gao, Norman J Haughey, M Christine Zink, Janice E Clements, Nicholas S Kim, Gabriel Van De Walle, Brigid K Jensen, Robert Vassar, R Christopher Pierce, Alexander J Gill, Dennis L Kolson, J Alan Diehl, Joseph L Mankowski, Kelly L Jordan-Sciutto
Mounting evidence implicates antiretroviral (ARV) drugs as potential contributors to the persistence and evolution of clinical and pathological presentation of HIV-associated neurocognitive disorders in the post-ARV era. Based on their ability to induce endoplasmic reticulum (ER) stress in various cell types, we hypothesized that ARV-mediated ER stress in the central nervous system resulted in chronic dysregulation of the unfolded protein response and altered amyloid precursor protein (APP) processing. We used in vitro and in vivo models to show that HIV protease inhibitor (PI) class ARVs induced neuronal damage and ER stress, leading to PKR-like ER kinase-dependent phosphorylation of the eukaryotic translation initiation factor 2α and enhanced translation of β-site APP cleaving enzyme-1 (BACE1)...
January 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/27992964/pkr-signalling-and-paradigms-of-cardiometabolic-syndrome
#11
REVIEW
Jaspreet Kalra, Arti Dhar
Metabolic syndrome (Met S) is a collection of the most severe cardio-metabolic risk factors that encompasses raised fasting plasma glucose, dyslipidemia, insulin resistance, obesity and hypertension. The precise mechanism underlying the pathogenesis of Met S remains unclear. More often oxidative stress, inflammation and apoptosis are implicated in its etiology. Recently, double stranded RNA dependent protein kinase has been found to intersect at the crossroad of oxidative stress, inflammation and apoptosis in several metabolic diseases...
December 19, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27988795/a-novel-anti-viral-role-for-stat3-in-ifn-%C3%AE-signalling-responses
#12
Rebecca Mahony, Siobhán Gargan, Kim L Roberts, Nollaig Bourke, Sinead E Keating, Andrew G Bowie, Cliona O'Farrelly, Nigel J Stevenson
The cytokine, Interferon (IFN)-α, induces a wide spectrum of anti-viral mediators, via the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. STAT1 and STAT2 are well characterised to upregulate IFN-stimulated gene (ISG) expression; but even though STAT3 is also activated by IFN-α, its role in anti-viral ISG induction is unclear. Several viruses, including Hepatitis C and Mumps, reduce cellular STAT3 protein levels, via the promotion of ubiquitin-mediated proteasomal degradation...
December 17, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27987116/roles-of-pkr-in-differentiation-and-apoptosis-of-bone-related-cells
#13
REVIEW
Tatsuji Haneji
Double-stranded RNA-dependent protein kinase (PKR) is a serine/threonine protein kinase which is activated by double-stranded RNAs and related to several signal transduction pathways. To examine the effects of PKR on bone metabolism, we established PKR-K/R mutant cells in which amino acid lysine at 296 is substituted with arginine. PKR regulated apoptosis in osteoblastic cells via nuclear factor kappa-B (NF-κB) cascade. MC3T3-E1 cells cultured with osteoblast differentiation medium differentiated into osteoblasts, while the mutant cells did not differentiate into osteoblasts...
December 16, 2016: Anatomical Science International
https://www.readbyqxmd.com/read/27981457/bariatric-surgery-ameliorates-diabetic-cardiac-dysfunction-by-inhibiting-er-stress-in-a-diabetic-rat-model
#14
Xiaoqian Zhang, Shaozhuang Liu, Guangyong Zhang, Mingwei Zhong, Teng Liu, Meng Wei, Dong Wu, Xin Huang, Yugang Cheng, Qunzheng Wu, Sanyuan Hu
BACKGROUND: Cardiac dysfunction is a severe complication of diabetes, with no effective treatment. Currently, bariatric surgery is more and more widely used to attenuate diabetes-associated diseases. The mechanism is not clear. Endoplasmic reticulum (ER) stress-dependent apoptosis has been observed in the progression of diabetic myocardium damage. Therefore, this research was designed to investigate the effects of different bariatric procedures on cardiac dysfunction via ER stress-induced cardiomyocyte apoptosis pathway in a diabetic rat model...
December 15, 2016: Obesity Surgery
https://www.readbyqxmd.com/read/27974558/mechanism-of-pkr-inhibition-by-human-cytomegalovirus-ptrs1
#15
Heather A Vincent, Benjamin Ziehr, Nathaniel J Moorman
: Double stranded RNAs (dsRNA) produced during human cytomegalovirus (HCMV) infection activate the antiviral kinase PKR, which potently inhibits virus replication. The HCMV pTRS1 and pIRS1 proteins antagonize PKR to promote HCMV protein synthesis and replication, however the mechanism by which pTRS1 inhibits PKR is unclear. PKR activation occurs in a three-step cascade. First, binding to dsRNA triggers PKR homodimerizaton. PKR dimers then autophosporylate, leading to a conformational shift that exposes the binding site for the PKR substrate eIF2α...
December 14, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27933051/short-interfering-rna-inhibits-rift-valley-fever-virus-replication-and-degradation-of-protein-kinase-r-in-human-cells
#16
Bonto Faburay, Juergen A Richt
Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing severe outbreaks in humans and livestock in sub-Saharan Africa and the Arabian Peninsula. Human infections are characterized by fever, sometimes leading to encephalitis, retinitis, hemorrhagic fever, and occasionally death. There are currently no fully licensed vaccines or effective therapies for human use. Gene silencing mediated by double-stranded short interfering RNA (siRNA) is a sequence-specific, highly conserved mechanism in eukaryotes, which serves as an antiviral defense mechanism...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27932618/the-roles-of-unfolded-protein-response-pathways-in-chlamydia-pathogenesis
#17
Zenas George, Yusuf Omosun, Anthony A Azenabor, James Partin, Kahaliah Joseph, Debra Ellerson, Qing He, Francis Eko, Claudiu Bandea, Pavel Svoboda, Jan Pohl, Carolyn M Black, Joseph U Igietseme
Chlamydia is an obligate intracellular bacterium that relies on host cell for essential nutrients and ATP for a productive infection. Although the unfolded protein response (UPR) plays a major role in certain microbial infectivity, its role in chlamydial pathogenesis is unknown. We hypothesized that Chlamydia induces UPR and exploits it to upregulate host cell uptake and metabolism of glucose, production of ATP, phospholipids and other molecules required for its replicative development and host survival. Using a combination of biochemical and pathway inhibition assays, we showed that the three UPR pathway transducers: Protein kinase RNA-activated (PKR)-like ER kinase (PERK), Inositol-requiring enzyme-1α (IRE1α), and Activating transcription factor-6α (ATF6α) were activated during Chlamydia infection...
December 8, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27929137/inhibition-of-pkr-protects-against-h2o2-induced-injury-on-neonatal-cardiac-myocytes-by-attenuating-apoptosis-and-inflammation
#18
Yongyi Wang, Min Men, Bo Xie, Jianggui Shan, Chengxi Wang, Jidong Liu, Hui Zheng, Wengang Yang, Song Xue, Changfa Guo
Reactive oxygenation species (ROS) generated from reperfusion results in cardiac injury through apoptosis and inflammation, while PKR has the ability to promote apoptosis and inflammation. The aim of the study was to investigate whether PKR is involved in hydrogen peroxide (H2O2) induced neonatal cardiac myocytes (NCM) injury. In our study, NCM, when exposed to H2O2, resulted in persistent activation of PKR due to NCM endogenous RNA. Inhibition of PKR by 2-aminopurine (2-AP) or siRNA protected against H2O2 induced apoptosis and injury...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27929099/stat1-is-essential-for-the-inhibition-of-hepatitis-c-virus-replication-by-interferon-%C3%AE-but-not-by-interferon-%C3%AE
#19
Shota Yamauchi, Kenji Takeuchi, Kazuyasu Chihara, Chisato Honjoh, Yuji Kato, Hatsumi Yoshiki, Hak Hotta, Kiyonao Sada
Interferon-α (IFN-α) and IFN-λ are structurally distinct cytokines that bind to different receptors, but induce expression of similar sets of genes through Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathways. The difference between IFN-α and IFN-λ signaling remains poorly understood. Here, using the CRISPR/Cas9 system, we examine the role of STAT1 and STAT2 in the inhibition of hepatitis C virus (HCV) replication by IFN-α and IFN-λ. Treatment with IFN-α increases expression of IFN-stimulated genes (ISGs) such as double-stranded RNA-activated protein kinase (PKR) and decreases viral RNA and protein levels in HCV-infected Huh-7...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27928012/emergence-of-a-viral-rna-polymerase-variant-during-gene-copy-number-amplification-promotes-rapid-evolution-of-vaccinia-virus
#20
Kelsey R Cone, Zev N Kronenberg, Mark Yandell, Nels C Elde
: Viruses are under relentless selective pressure from host immune defenses. To study how poxviruses adapt to innate immune detection pathways, we performed serial infections of vaccinia virus in primary human cells. Independent courses of experimental evolution with a recombinant strain lacking E3L revealed several high frequency point mutations in conserved poxvirus genes, suggesting important roles for essential poxvirus proteins in innate immune subversion. Two distinct mutations were identified in the viral RNA polymerase gene A24R, which seem to act through different mechanisms to increase virus replication...
December 7, 2016: Journal of Virology
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