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eIf2a

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https://www.readbyqxmd.com/read/29626156/the-gcn2-eif2a-pathway-connects-iron-and-amino-acid-homeostasis-in-saccharomyces-cerevisiae
#1
Marcos Caballero-Molada, María D Planes, Helena Benlloch, Sergio Atares, Miguel A Naranjo, Ramón Serrano
In eukaryotic cells amino acid biosynthesis is feedback inhibited by amino acids through inhibition of conserved protein kinase Gcn2. This decreases phosphorylation of initiation factor eIF2a resulting in general activation of translation but inhibition of translation of mRNA for transcription factor (TF) Gcn4 in yeast or ATF4 in mammals. These TFs are positive regulators of amino acid biosynthetic genes. As several enzymes of amino acid biosynthesis contain iron-sulfur clusters and iron excess is toxic, iron and amino acid homeostasis should be coordinated...
April 6, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29595074/alleviation-of-hippocampal-endoplasmic-reticulum-stress-by-allomyrina-dichotoma-larvae-extract
#2
Jongwan Kim, Md Nazmul Haque, Tae-Won Goo, Il Soo Moon
In the brain, endoplasmic reticulum (ER) stress results in synaptic dysfunction and eventually leads to neurodegeneration. Allomyrina dichotoma larvae are a Chinese ethnomedicine and are widely used in East Asia. In the present study, we investigated the ability of ethanol extract of A. dichotoma larvae (ADE) to improve synaptic structure and function by activating unfolded protein response (UPR) under ER stress in animal and neuron culture models. ER stress was induced in obese mice fed a high fat diet (HFD) or by treating dissociated cultures of rat embryonic (E19) hippocampal neurons with tunicamycin (TM)...
March 29, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29510614/expression-of-immunoproteasome-subunit-lmp7-in-breast-cancer-and-its-association-with-immune-related-markers
#3
Miseon Lee, In Hye Song, Sun-Hee Heo, Young-Ae Kim, In Ah Park, Won Seon Bang, Hye Seon Park, Gyungyub Gong, Hee Jin Lee
Purpose: In the presence of interferon, proteasome subunits are replaced by their inducible counterparts to form an immunoproteasome (IP) plays a key role in generation of antigenic peptides presented by MHC class I molecules, leading to elicitation of a T cell‒mediated immune response. Although the roles of IP in other cancers, and inflammatory diseases have been extensively studied, its significance in breast cancer is unclear. Materials and Methods: We investigated the expression of LMP7, an IP subunit, and its relationship with immune system components in two breast cancer cohorts...
February 26, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29487587/the-initiation-factors-eif2-eif2a-eif2d-eif4a-and-eif4g-are-not-involved-in-translation-driven-by-hepatitis-c-virus-ires-in-human-cells
#4
Esther González-Almela, Hugh Williams, Miguel A Sanz, Luis Carrasco
Animal viruses have evolved a variety of strategies to ensure the efficient translation of their mRNAs. One such strategy is the use of internal ribosome entry site (IRES) elements, which circumvent the requirement for some eukaryotic initiation factors (eIFs). Much effort has been directed to unravel the precise mechanism of translation initiation by hepatitis C virus (HCV) mRNA. In the present study, we examined the involvement of several eIFs in HCV IRES-driven translation in human cells in a comparative analysis with mRNAs bearing the encephalomyocarditis virus or the Cricket paralysis virus IRES element...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29274870/villin-1-and-gelsolin-regulate-changes-in-actin-dynamics-that-affect-cell-survival-signaling-pathways-and-intestinal-inflammation
#5
Swati Roy, Amin Esmaeilniakooshkghazi, Srinivas Patnaik, Yaohong Wang, Sudeep P George, Afzal Ahrorov, Jason K Hou, Allan J Herron, Hiromi Sesaki, Seema Khurana
BACKGROUND & AIMS: Cell stress signaling pathways result in phosphorylation of the eukaryotic translation initiation factor 2 subunit alpha (EIF2S1 or EIF2A), which affects regulation of protein translation. Translation reprogramming mitigates stress by activating pathways that result in autophagy and cell death, to eliminate damaged cells. Actin is modified during stress and EIF2A is dephosphorylated to restore homeostasis. It is not clear how actin affects EIF2A signaling. We studied the actin-binding proteins villin 1 (VIL1) and gelsolin (GSN) in intestinal epithelial cells (IECs) to determine whether they respond to cell stress response and affect signaling pathways...
December 21, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29219623/usual-normalization-strategies-for-gene-expression-studies-impair-the-detection-and-analysis-of-circadian-patterns
#6
Diego de Siqueira Figueredo, Mayara Rodrigues Barbosa, Daniel Gomes Coimbra, José Luiz Araújo Dos Santos, Ellyda Fernanda Lopes Costa, Bruna Del Vechio Koike, Magna Suzana Alexandre Moreira, Tiago Gomes de Andrade
Recent studies have shown that transcriptomes from different tissues present circadian oscillations. Therefore, the endogenous variation of total RNA should be considered as a potential bias in circadian studies of gene expression. However, normalization strategies generally include the equalization of total RNA concentration between samples prior to cDNA synthesis. Moreover, endogenous housekeeping genes (HKGs) frequently used for data normalization may exhibit circadian variation and distort experimental results if not detected or considered...
December 8, 2017: Chronobiology International
https://www.readbyqxmd.com/read/29065505/kinases-of-eif2a-switch-translation-of-mrna-subset-during-neuronal-plasticity
#7
REVIEW
Ekaterina Chesnokova, Natalia Bal, Peter Kolosov
Compared to other types of cells, neurons express the largest number of diverse mRNAs, including neuron-specific ones. This mRNA diversity is required for neuronal function, memory storage, maintenance and retrieval. Regulation of translation in neurons is very complicated and involves various proteins. Some proteins, implementing translational control in other cell types, are used by neurons for synaptic plasticity. In this review, we discuss the neuron-specific activity of four kinases: protein kinase R (PKR), PKR-like endoplasmic reticulum kinase (PERK), general control nonderepressible 2 kinase (GCN2), and heme-reguated eIF2α kinase (HRI), the substrate for which is α-subunit of eukaryotic initiation factor 2 (eIF2α)...
October 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28870519/sigma-1-receptor-knockout-increases-%C3%AE-synuclein-aggregation-and-phosphorylation-with-loss-of-dopaminergic-neurons-in-substantia-nigra
#8
Juan Hong, Ling Wang, Tingting Zhang, Baofeng Zhang, Ling Chen
Sigma-1 receptor (σ1 R) is expressed in dopaminergic neurons of substantia nigra. Here, we show that σ1 R knockout (σ1 R-/- ) mice, at age 6-12 months, appeared with age-related loss of dopaminergic neurons and decline of motor coordination. Levels of α-synuclein (αSyn) oligomers and fibrillar αSyn in substantia nigra of σ1 R-/- mice were age-dependently increased without the changes in αSyn monomers. The phosphorylation of αSyn monomers or oligomers in dopaminergic neurons was enhanced in σ1 R-/- mice...
November 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28729823/administration-of-tauroursodeoxycholic-acid-attenuates-early-brain-injury-via-akt-pathway-activation
#9
Dongdong Sun, Gang Gu, Jianhao Wang, Yan Chai, Yueshan Fan, Mengchen Yang, Xin Xu, Weiwei Gao, Fei Li, Dongpei Yin, Shuai Zhou, Xin Chen, Jianning Zhang
Traumatic brain injury (TBI) is one of the leading causes of trauma-induced mortality and disability, and emerging studies have shown that endoplasmic reticulum (ER) stress plays an important role in the pathophysiology of TBI. Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, has been reported to act as an ER stress inhibitor and chemical chaperone and to have the potential to attenuate apoptosis and inflammation. To study the effects of TUDCA on brain injury, we subjected mice to TBI with a controlled cortical impact (CCI) device...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28694302/up-regulation-of-ankdr49-a-poor-prognostic-factor-regulates-cell-proliferation-of-gliomas
#10
Chunyan Hao, Hubin Duan, Hao Li, Mingyang Pei, Yueting Liu, Yimin Fan, Ce Zhang
The Ankyrin repeat domain 49 (ANKRD49) is an evolutionarily conserved protein, which is related to mediate protein-protein interaction. However, the function of ANKRD49 in human glioma remains elusive. Through mining The Cancer Genome Atlas (TCGA) database, we found that the expression of ANKRD49 was increased in glioma tissues and that high expression of ANKRD49 was strongly associated with high disease grade and poor overall survival. To investigate the role of ANKRD49 in malignant glioma, lentivirus expressing shRNA targeting ANKRD49 was constructed in U251 and U87 malignant glioma cells...
July 10, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28674429/citrate-suppresses-tumor-growth-in-multiple-models-through-inhibition-of-glycolysis-the-tricarboxylic-acid-cycle-and-the-igf-1r-pathway
#11
Jian-Guo Ren, Pankaj Seth, Huihui Ye, Kun Guo, Jun-Ichi Hanai, Zaheed Husain, Vikas P Sukhatme
In this study we have tested the efficacy of citrate therapy in various cancer models. We found that citrate administration inhibited A549 lung cancer growth and additional benefit accrued in combination with cisplatin. Interestingly, citrate regressed Ras-driven lung tumors. Further studies indicated that citrate induced tumor cell differentiation. Additionally, citrate treated tumor samples showed significantly higher infiltrating T-cells and increased blood levels of numerous cytokines. Moreover, we found that citrate inhibited IGF-1R phosphorylation...
July 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28668332/ethanol-induced-pge2-up-regulates-a%C3%AE-production-through-pka-creb-signaling-pathway
#12
Amr Ahmed Gabr, Hyun Jik Lee, Xaykham Onphachanh, Young Hyun Jung, Jun Sung Kim, Chang Woo Chae, Ho Jae Han
Ethanol abuse aggravates dementia-associated cognitive defects through the progression of Alzheimer's disease (AD) pathophysiology. Beta-site APP-cleaving enzyme 1 (BACE1) has been considered as a key regulator of AD pathogenesis by controlling amyloid beta peptide (Aβ) accumulation. In addition, previous studies reported that endoplasmic reticulum (ER) stress and neuroinflammation have been proposed in ethanol-induced neurodegeneration. Thus, we investigated the role of ER stress and PGE2, a neuroinflammation mediator, in the ethanol-stimulated BACE1 expression and Aβ production...
November 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28546432/regulation-of-the-endoplasmic-reticulum-stress-response-and-neuroprotective-effects-of-acupuncture-on-brain-injury-caused-by-heroin-addiction
#13
Yong-Long Gao, Yang Zhang, Jiang-Peng Cao, Sheng-Bing Wu, Xing-Hui Cai, Yan-Chun Zhang, Rong-Jun Zhang, Xiao-Ge Song, Li-Da Zhang
OBJECTIVES: To evaluate regulation of the endoplasmic reticulum stress (ERS) response by acupuncture and to investigate its neuroprotective effect on brain injury caused by heroin addiction. METHODS: A total of 48 male Sprague-Dawley rats were randomly divided into a healthy control group (Control), an untreated heroin exposed group (Heroin) and a heroin exposed group receiving electroacupuncture (EA) treatment at GV14 and GV20 (Heroin+acupuncture) with n=16 rats per group...
October 2017: Acupuncture in Medicine: Journal of the British Medical Acupuncture Society
https://www.readbyqxmd.com/read/28389244/colostrum-oxytocin-modulates-cellular-stress-response-inflammation-and-autophagy-markers-in-newborn-rat-gut-villi
#14
Benjamin Y Klein, Hadassah Tamir, Robert J Ludwig, Sara B Glickstein, Martha G Welch
Little is known about the role of oxytocin (OT) in colostrum during early gut colonization. We previously showed that transient OT receptor (OTR) expression on newborn rat enterocytes coincides with the milk-suckling period, and that OT activates endoplasmic reticulum stress sensors in cultured enterocytes. Here, we explored whether colostrum-OT attenuates stress in newborn villi primed and unprimed by colostrum by measuring levels of stress markers including BiP (an ER chaperone), eIF2a (translation initiation factor), and pPKR (eIF2a kinase)...
May 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28256794/laser-capture-microdissection-enables-transcriptomic-analysis-of-dividing-and-quiescent-liver-stages-of-plasmodium-relapsing-species
#15
Roger Cubi, Shruthi S Vembar, Anne Biton, Jean-Francois Franetich, Mallaury Bordessoulles, Daniel Sossau, Gigliola Zanghi, Henriette Bosson-Vanga, Magalie Benard, Alicia Moreno, Nathalie Dereuddre-Bosquet, Roger Le Grand, Artur Scherf, Dominique Mazier
Dormant liver stage forms (hypnozoites) of the malaria parasite Plasmodium vivax present major hurdles to control and eradicate infection. Despite major research efforts, the molecular composition of hypnozoites remains ill defined. Here, we applied a combination of state-of-the-art technologies to generate the first transcriptome of hypnozoites. We developed a robust laser dissection microscopy protocol to isolate individual Plasmodium cynomolgi hypnozoites and schizonts from infected monkey hepatocytes and optimized RNA-seq analysis to obtain the first transcriptomes of these stages...
August 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28240315/translation-of-sindbis-subgenomic-mrna-is-independent-of-eif2-eif2a-and-eif2d
#16
Miguel Angel Sanz, Esther González Almela, Luis Carrasco
Translation of Sindbis virus subgenomic mRNA (sgmRNA) can occur after inactivation of eIF2 by phosphorylation in mammalian cells. Several studies have suggested that eIF2 can be replaced by eIF2A or eIF2D. HAP1 human cell lines knocked-out for eIF2A, eIF2D or both by CRISPR/Cas9 genome engineering were compared with wild-type (WT) cells to test the potential role of eIF2A and eIF2D in translation. Sindbis virus infection was comparable between the four cell lines. Moreover, synthesis of viral proteins during late stage infection was similar in all four cell lines despite the fact that eIF2α became phosphorylated...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202752/human-herpesvirus-6a-exhibits-restrictive-propagation-with-limited-activation-of-the-protein-kinase-r-eif2%C3%AE-stress-pathway
#17
Eyal Sharon, Niza Frenkel
The eIF2α protein plays a critical role in the regulation of translation. The production of double-stranded RNA (dsRNA) during viral replication can activate protein kinase R (PKR), which phosphorylates eIF2α, leading to inhibition of the initial step of translation. Many viruses have evolved gene products targeting the PKR-eIF2a pathway, indicating its importance in antiviral defense. In the present study, we focused on alternations of PKR-eIF2a pathway during human herpesvirus 6A (HHV-6A) infection while monitoring viral gene expression and infectious viral yields...
May 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28174276/synergistic-antileukemic-therapies-in-notch1-induced-t-all
#18
Marta Sanchez-Martin, Alberto Ambesi-Impiombato, Yue Qin, Daniel Herranz, Mukesh Bansal, Tiziana Girardi, Elisabeth Paietta, Martin S Tallman, Jacob M Rowe, Kim De Keersmaecker, Andrea Califano, Adolfo A Ferrando
The Notch1 gene is a major oncogenic driver and therapeutic target in T-cell acute lymphoblastic leukemia (T-ALL). However, inhibition of NOTCH signaling with γ-secretase inhibitors (GSIs) has shown limited antileukemic activity in clinical trials. Here we performed an expression-based virtual screening to identify highly active antileukemic drugs that synergize with NOTCH1 inhibition in T-ALL. Among these, withaferin A demonstrated the strongest cytotoxic and GSI-synergistic antileukemic effects in vitro and in vivo...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28148553/perk-activation-mitigates-tau-pathology-in-vitro-and-in-vivo
#19
Julius Bruch, Hong Xu, Thomas W Rösler, Anderson De Andrade, Peer-Hendrik Kuhn, Stefan F Lichtenthaler, Thomas Arzberger, Konstanze F Winklhofer, Ulrich Müller, Günter U Höglinger
The RNA-like endoplasmic reticulum kinase (PERK) is genetically associated with the tauopathy progressive supranuclear palsy (PSP). To elucidate the functional mechanisms underlying this association, we explored PERK activity in brains of PSP patients and its function in three tauopathy models (cultured human neurons overexpressing 4-repeat wild-type tau or treated with the environmental neurotoxin annonacin, and P301S tau transgenic mice). In vitro , treatment with a pharmacological PERK activator CCT020312 or PERK overexpression reduced tau phosphorylation, tau conformational change and 4-repeat tau isoforms, and increased cell viability...
March 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28108459/translation-from-alternate-start-sites-enriches-oncogenic-proteins
#20
(no author information available yet)
eIF2A promotes translation from upstream initiation sites during tumor initiation.
January 20, 2017: Cancer Discovery
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