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https://www.readbyqxmd.com/read/28729823/administration-of-tauroursodeoxycholic-acid-attenuates-early-brain-injury-via-akt-pathway-activation
#1
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
#2
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
#3
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
#4
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...
June 28, 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
#5
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...
May 25, 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
#6
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
#7
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
#8
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
#9
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
#10
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%C3%A2-vitro-and-in%C3%A2-vivo
#11
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
#12
(no author information available yet)
eIF2A promotes translation from upstream initiation sites during tumor initiation.
January 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28077873/translation-from-unconventional-5-start-sites-drives-tumour-initiation
#13
Ataman Sendoel, Joshua G Dunn, Edwin H Rodriguez, Shruti Naik, Nicholas C Gomez, Brian Hurwitz, John Levorse, Brian D Dill, Daniel Schramek, Henrik Molina, Jonathan S Weissman, Elaine Fuchs
We are just beginning to understand how translational control affects tumour initiation and malignancy. Here we use an epidermis-specific, in vivo ribosome profiling strategy to investigate the translational landscape during the transition from normal homeostasis to malignancy. Using a mouse model of inducible SOX2, which is broadly expressed in oncogenic RAS-associated cancers, we show that despite widespread reductions in translation and protein synthesis, certain oncogenic mRNAs are spared. During tumour initiation, the translational apparatus is redirected towards unconventional upstream initiation sites, enhancing the translational efficiency of oncogenic mRNAs...
January 26, 2017: Nature
https://www.readbyqxmd.com/read/27987431/acriflavine-inhibits-acquired-drug-resistance-by-blocking-the-epithelial-to-mesenchymal-transition-and-the-unfolded-protein-response
#14
Jeroen Dekervel, Ashenafi Bulle, Petra Windmolders, Diether Lambrechts, Eric Van Cutsem, Chris Verslype, Jos van Pelt
Epithelial-to-mesenchymal transition (EMT) is linked to tumor invasion, drug resistance and aggressive disease and this is largely dependent on the cell's microenvironment. Acriflavine (ACF) is an old antibacterial drug recently also suggested as anticancer agent and HIF inhibitor. We wanted to study the effect of acriflavine on EMT in different human cancer models. Pancreatic cancer cells (Panc-1) were exposed to TGF-β1 or cobalt chloride (to mimick severe hypoxia) to induce EMT. For our third model we exposed HepG2 liver cancer cells to sorafenib which resulted in development of acquired drug resistance with strong features of EMT and aggressive behavior...
December 14, 2016: Translational Oncology
https://www.readbyqxmd.com/read/27899592/an-mrna-specific-trnai-carrier-eif2a-plays-a-pivotal-role-in-cell-proliferation-under-stress-conditions-stress-resistant-translation-of-c-src-mrna-is-mediated-by-eif2a
#15
Oh Sung Kwon, Sihyeon An, Eunah Kim, Jinbae Yu, Ka Young Hong, Jae Seung Lee, Sung Key Jang
c-Src, a non-receptor protein tyrosine kinase, activates NF-κB and STAT3, which in turn triggers the transcription of anti-apoptosis- and cell cycle-related genes. c-Src protein regulates cell proliferation, cell motility and programmed cell death. And the elevated level of activated c-Src protein is related with solid tumor generation. Translation of c-Src mRNA is directed by an IRES element which mediates persistent translation under stress conditions when translation of most mRNAs is inhibited by a phosphorylation of the alpha subunit of eIF2 carrying the initiator tRNA (tRNAi) to 40S ribosomal subunit under normal conditions...
January 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27816613/tris-1-3-dichloro-2-propyl-phosphate-induced-apoptotic-signaling-pathways-in-sh-sy5y-neuroblastoma-cells
#16
Ruiwen Li, Peijiang Zhou, Yongyong Guo, Jae-Seong Lee, Bingsheng Zhou
Tris (1, 3-dichloro-2-propyl) phosphate (TDCIPP, also known as TDCPP), an extensively used flame retardant, is frequently detected in the environment and biota. Recent studies have shown that TDCIPP has neurotoxic effects. In this study, we determined the mechanisms of TDCIPP-induced neurotoxicity in human neuroblastoma (SH-SY5Y) cells. By using morphological examination, flow cytometry, and mitochondrial membrane potential (ΔYm) measurement, we confirmed that exposure to TDCIPP caused apoptosis accompanied by the activation of apoptosis-related genes (e...
November 2, 2016: Neurotoxicology
https://www.readbyqxmd.com/read/27790092/upstream-open-reading-frames-located-in-the-leader-of-protein-kinase-m%C3%AE-mrna-regulate-its-translation
#17
Natalia V Bal, Denis Susorov, Ekaterina Chesnokova, Artem Kasianov, Tatiana Mikhailova, Elena Alkalaeva, Pavel M Balaban, Peter Kolosov
For protein synthesis that occurs locally in dendrites, the translational control mechanisms are much more important for neuronal functioning than the transcription levels. Here, we show that uORFs (upstream open reading frames) in the 5' untranslated region (5'UTR) play a critical role in regulation of the translation of protein kinase Mζ (PKMζ). Elimination of these uORFs activates translation of the reporter protein in vitro and in primary cultures of rat hippocampal neurons. Using cell-free translation systems, we demonstrate that translational initiation complexes are formed only on uORFs...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27686860/the-eif2a-knockout-mouse
#18
Andrei Golovko, Artyom Kojukhov, Bo-Jhih Guan, Benjamin Morpurgo, William C Merrick, Barsanjit Mazumder, Maria Hatzoglou, Anton A Komar
Eukaryotic initiation factor 2A (eIF2A) is a 65-kDa protein that was first identified in the early 1970s as a factor capable of stimulating initiator methionyl-tRNAi (Met-tRNA(Met)i) binding to 40S ribosomal subunits in vitro. However, in contrast to the eIF2, which stimulates Met-tRNA(Met)i binding to 40S ribosomal subunits in a GTP-dependent manner, eIF2A didn't reveal any GTP-dependence, but instead was found to direct binding of the Met-tRNA(Met)i to 40S ribosomal subunits in a codon-dependent manner. eIF2A appears to be highly conserved across eukaryotic species, suggesting conservation of function in evolution...
November 16, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27660012/gu-ben-fang-xiao-decoction-attenuates-sustained-airway-inflammation-by-suppressing-er-stress-response-in-a-murine-asthma-remission-model-of-respiratory-syncytial-virus-infection
#19
Yuan Lu, Jian-Ya Xu, Xiao-Hua Zhang, Xia Zhao
ETHNOPHARMACOLOGICAL RELEVANCE: In recent years, asthma has increased dramatically in prevalence with a considerable economic burden all over the world. Long-term remission should be regarded as the promising and meaningful therapeutic goal in asthma management. However, the precise definition criteria and rational therapies for asthma remission have not been well-established. In academia, there is a consensus that even in those who develop asymptomatic remission of asthma, persistent airway inflammation is ubiquitous...
November 4, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27626202/the-nedd8-activating-enzyme-inhibitor-pevonedistat-activates-the-eif2%C3%AE-and-mtor-pathways-inducing-upr-mediated-cell-death-in-acute-lymphoblastic-leukemia
#20
Gilles M Leclerc, Shuhua Zheng, Guy J Leclerc, Joanna DeSalvo, Ronan T Swords, Julio C Barredo
Acute lymphoblastic leukemia (ALL) is the leading cause of cancer-related death in children, and cure rates for adults remain dismal. Further, effective treatment strategies for relapsed/refractory ALL remain elusive. We previously uncovered that ALL cells are prone to apoptosis via endoplasmic reticulum (ER) stress/unfolded protein response (UPR)-mediated mechanisms. We investigated the antineoplastic activity of pevonedistat(®), a novel NEDD8-activating enzyme inhibitor that targets E3 cullin-RING ligases (CRLs) dependent proteasomal protein degradation, in ALL...
November 2016: Leukemia Research
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