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https://www.readbyqxmd.com/read/29328442/identification-of-differentially-expressed-genes-and-regulatory-relationships-in-huntington-s-disease-by-bioinformatics-analysis
#1
Xiaoyu Dong, Shuyan Cong
Huntington's disease (HD) is an inherited, progressive neurodegenerative disease caused by a CAG expansion in the huntingtin (HTT) gene; various dysfunctions of biological processes in HD have been proposed. However, at present the exact pathogenesis of HD is not fully understood. The present study aimed to explore the pathogenesis of HD using a computational bioinformatics analysis of gene expression. GSE11358 was downloaded from the Gene Expression Omnibus andthe differentially expressed genes (DEGs) in the mutant HTT knock‑in cell model STHdhQ111/Q111 were predicted...
January 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29321042/type-i-ifn-signature-in-childhood-onset-systemic-lupus-erythematosus-a-conspiracy-of-dna-and-rna-sensing-receptors
#2
M Javad Wahadat, Iris L A Bodewes, Naomi I Maria, Cornelia G van Helden-Meeuwsen, Annette van Dijk-Hummelman, Eline C Steenwijk, Sylvia Kamphuis, Marjan A Versnel
BACKGROUND: Childhood-onset systemic lupus erythematosus (cSLE) is an incurable multi-systemic autoimmune disease. Interferon type I (IFN-I) plays a pivotal role in the pathogenesis of SLE. The objective of this study was to assess the prevalence of the IFN-I signature and the contribution of cytosolic nucleic acid receptors to IFN-I activation in a cohort of primarily white cSLE patients. METHODS: The IFN-I score (positive or negative), as a measure of IFN-I activation, was assessed using real-time quantitative PCR (RT-PCR) expression values of IFN-I signature genes (IFI44, IFI44L, IFIT1, Ly6e, MxA, IFITM1) in CD14+ monocytes of cSLE patients and healthy controls (HCs)...
January 10, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29320742/defective-mitochondrial-trna-taurine-modification-activates-global-proteostress-and-leads-to-mitochondrial-disease
#3
Md Fakruddin, Fan-Yan Wei, Takeo Suzuki, Kana Asano, Takashi Kaieda, Akiko Omori, Ryoma Izumi, Atsushi Fujimura, Taku Kaitsuka, Keishi Miyata, Kimi Araki, Yuichi Oike, Luca Scorrano, Tsutomu Suzuki, Kazuhito Tomizawa
A subset of mitochondrial tRNAs (mt-tRNAs) contains taurine-derived modifications at 34U of the anticodon. Loss of taurine modification has been linked to the development of mitochondrial diseases, but the molecular mechanism is still unclear. Here, we showed that taurine modification is catalyzed by mitochondrial optimization 1 (Mto1) in mammals. Mto1 deficiency severely impaired mitochondrial translation and respiratory activity. Moreover, Mto1-deficient cells exhibited abnormal mitochondrial morphology owing to aberrant trafficking of nuclear DNA-encoded mitochondrial proteins, including Opa1...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29317239/protective-effect-of-mitochondrial-targeted-antioxidant-mitoq-against-iron-ion-56fe-radiation-induced-brain-injury-in-mice
#4
Lu Gan, Zhenhua Wang, Jing Si, Rong Zhou, Chao Sun, Yang Liu, Yancheng Ye, Yanshan Zhang, Zhiyuan Liu, Hong Zhang
Exposure to iron ion 56Fe radiation (IR) during space missions poses a significant risk to the central nervous system and radiation exposure is intimately linked to the production of reactive oxygen species (ROS). MitoQ is a mitochondria-targeted antioxidant that has been shown to decrease oxidative damage and lower mitochondrial ROS in a number of animal models. Therefore, the present study aimed to investigate role of the mitochondrial targeted antioxidant MitoQ against 56Fe particle irradiation-induced oxidative damage and mitochondria dysfunction in the mouse brains...
January 6, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29312595/pyruvate-kinase-m2-phosphorylates-h2ax-and-promotes-genomic-instability-in-human-tumor-cells
#5
Li Xia, Kang Qin, Xin-Ran Wang, Xiao-Ling Wang, Ai-Wu Zhou, Guo-Qiang Chen, Ying Lu
Pyruvate kinase (PK) catalyzes the conversion of phosphoenolpyruvate and ADP to pyruvate and ATP, a rate-limiting reaction in glycolysis. M2 isoform of PK (PKM2) is the predominant form of PK expressed in tumors. In addition to its well established cytosolic functions as a glycolytic enzyme, PKM2 displays nuclear localization and important nonmetabolic functions in tumorigenesis. Herein, we report that nuclear PKM2 interacts with histone H2AX under DNA damage conditions. Depletion of PKM2 decreased the level of serine 139-phosphorylated H2AX (γ-H2AX) in response to DNA damage...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29298890/full-length-glycosylated-gag-of-murine-leukemia-virus-can-associate-with-the-viral-envelope-as-a-type-i-integral-membrane-protein
#6
Tyler Milston Renner, Kasandra Bélanger, Cindy Lam, Maria Rosales Gerpe, Joanne Eileen McBane, Marc-André Langlois
The glycosylated Gag protein (gPr80) of murine leukemia viruses (MLVs) has been shown to exhibit multiple roles in facilitating retrovirus release, infection and resistance to host-encoded retroviral restriction factors such as APOBEC3, SERINC3 and SERINC5. One way gPr80 helps MLVs escape host innate immune restriction is by increasing capsid stability, a feature that protects viral replication intermediates from being detected by cytosolic DNA sensors. gPr80 also increases the resistance of MLVs against deamination and restriction by mouse APOBEC3 (mA3)...
January 3, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29298887/evasion-of-cytosolic-dna-stimulated-innate-immune-responses-by-hsv-1
#7
Chunfu Zheng
Recognition of virus-derived nucleic acids by host pattern recognition receptors (PRRs) is crucial for early defense against viral infections. Recent studies revealed that PRRs also include several newly identified DNA sensors, most of which could activate the downstream adaptor stimulator of interferon genes (STING) and lead to the production of host antiviral factors. Herpes simplex virus type 1 (HSV-1) is extremely successful to establish an effective infection due to its capacity to counteract host innate antiviral responses...
January 3, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29288497/the-role-of-trna-synthetases-in-neurological-and-neuromuscular-disorders
#8
REVIEW
Veronika Boczonadi, Matthew J Jennings, Rita Horvath
Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed enzymes responsible for charging tRNAs with their cognate amino acids, therefore essential for the first step in protein synthesis. Although the majority of protein synthesis happens in the cytosol, an additional translation apparatus is required to translate the 13 mitochondrial DNA-encoded proteins important in oxidative phosphorylation. Most ARS genes in these cellular compartments are distinct, but two genes are common, encoding aminoacyl-tRNA synthetases of glycine (GARS) and lysine (KARS) in both mitochondria and the cytosol...
December 30, 2017: FEBS Letters
https://www.readbyqxmd.com/read/29286126/bcl-2-overexpression-reduces-cisplatin-cytotoxicity-by-decreasing-er-mitochondrial-ca2-signaling-in-skov3-cells
#9
Lu Xu, Qi Xie, Ling Qi, Chunyan Wang, Na Xu, Weimin Liu, Yang Yu, Songyan Li, Ye Xu
Recent studies have revealed that a small amount of cisplatin can penetrate into the nucleus and induce intranuclear DNA damage. Specifically, most cisplatin accumulates in and stresses different organelles, including mitochondria, endoplasmic reticulum (ER) and the cytosol, where apoptosis signaling is activated and magnified. Bcl-2, which is mainly localized to ER and mitochondria, is identified as a key regulator of survival and apoptosis. Bcl-2 is reported to block cisplatin-induced apoptosis via regulating Ca2+ signaling in a variety of cancer cell lines...
December 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29284022/a-transcriptomics-approach-uncovers-novel-roles-for-poly-adp-ribosyl-ation-in-the-basal-defense-response-in-arabidopsis-thaliana
#10
Amy G Briggs, Lori C Adams-Phillips, Brian D Keppler, Sophia G Zebell, Kyle C Arend, April A Apfelbaum, Joshua A Smith, Andrew F Bent
Pharmacological inhibition of poly(ADP-ribose) polymerase (PARP) or loss of Arabidopsis thaliana PARG1 (poly(ADP-ribose) glycohydrolase) disrupt a subset of plant defenses. In the present study we examined the impact of altered poly(ADP-ribosyl)ation on early gene expression induced by the microbe-associate molecular patterns (MAMPs) flagellin (flg22) and EF-Tu (elf18). Stringent statistical analyses and filtering identified 178 genes having MAMP-induced mRNA abundance patterns that were altered by either PARP inhibitor 3-aminobenzamide (3AB) or PARG1 knockout...
2017: PloS One
https://www.readbyqxmd.com/read/29278807/myricetin-enhances-on-apoptosis-induced-by-serum-deprivation-in-pc12-cells-mediated-by-mitochondrial-signaling-pathway
#11
Gongxun Tan, Rachael A Uson-Lopez, Md Mostafizur Rahman, Toshiyuki Hosokawa, Takeshi Saito, Masaaki Kurasaki
Polyphenols have many beneficial effects and an effective disease therapeutic auxiliary drug. Previously, myricetin, a polyphenol, had been reported to possess various biological effects on human physiology. However, mechanism of myricetin on apoptosis induced in PC12 cells is still unclear. PC12 cells were treated with myricetin in two concentration levels comprising 0.1 and 1 μM under serum-free condition. As a result, morphological changes were observed using trypan blue assay. DNA fragmentation was determined by DNA ladder assay to evaluate DNA damage levels...
December 18, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29274491/photoactive-platinum-ii-complexes-of-nonsteroidal-anti-inflammatory-drug-naproxen-interaction-with-biological-targets-antioxidant-activity-and-cytotoxicity
#12
Payal Srivastava, Khushbu Singh, Madhu Verma, Sri Sivakumar, Ashis K Patra
The effect on the therapeutic efficacy of Pt(II) complexes on combining non-steroidal anti-inflammatory drugs (NSAIDs) is an attractive strategy to circumvent chronic inflammation mediated by cancer and metastasis. Two square-planar platinum(II) complexes: [Pt(dach)(nap)Cl] (1) and [Pt(dach)(nap)2] (2), where dach = (1R,2R)-dichloro(cyclohexane-1,2-diamine) and NSAID drug naproxen (nap), have been designed for studying their biological activity. The naproxen bound to the Pt(II) centre get released upon photoirradiation with low-power UV-A light as confirmed by the significant enhancement in emission intensities of the complexes...
December 8, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29248385/a-cytosolic-sensor-pmddx41-mediates-antiviral-immune-response-in-black-tiger-shrimp-penaeus-monodon
#13
Suthinee Soponpong, Piti Amparyup, Anchalee Tassanakajon
DEAD (Asp-Glu-Ala-Asp)-box polypeptide 41 (DDX41), a receptor belonging to the DExD family, has recently been identified as an intracellular DNA sensor in vertebrates. Here, we report on the identification and functional characterization of PmDDX41, the first cytosolic DNA sensor in shrimp. By searching a Penaeus monodon expressed sequence tag (EST) database (http://pmonodon.biotec.or.th), three cDNA fragments exhibiting similarity to DDX41 in various species were identified and assembled, resulting in a complete open reading frame of PmDDX41 that contains 1868-bp and encodes a putative protein of 620 amino acids...
December 14, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29247998/the-aim2-inflammasome-sensor-of-pathogens-and-cellular-perturbations
#14
REVIEW
Jérôme Lugrin, Fabio Martinon
Recognition of pathogens and altered self must be efficient and highly specific to orchestrate appropriate responses while limiting excessive inflammation and autoimmune reaction to normal self. AIM2 is a member of innate immune sensors that detects the presence of DNA, arguably the most conserved molecules in living organisms. However, AIM2 achieves specificity by detecting altered or mislocalized DNA molecules. It can detect damaged DNA, and the aberrant presence of DNA within the cytosolic compartment such as genomic DNA released into the cytosol upon loss of nuclear envelope integrity...
January 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29247853/cytosolic-sensing-of-immuno-stimulatory-dna-the-enemy-within
#15
REVIEW
Rekha Dhanwani, Mariko Takahashi, Sonia Sharma
In the cytoplasm, DNA is sensed as a universal danger signal by the innate immune system. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor/enzyme that catalyzes formation of 2'-5'-cGAMP, an atypical cyclic di-nucleotide second messenger that binds and activates the Stimulator of Interferon Genes (STING), resulting in recruitment of Tank Binding Kinase 1 (TBK1), activation of the transcription factor Interferon Regulatory Factor 3 (IRF3), and trans-activation of innate immune response genes, including type I Interferon cytokines (IFN-I)...
December 13, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29229477/puma-dependent-mitophagy-by-abrus-agglutinin-contributes-to-apoptosis-through-ceramide-generation
#16
Prashanta Kumar Panda, Prajna Paramita Naik, Biswa Ranjan Meher, Durgesh Nandini Das, Subhadip Mukhopadhyay, Prakash Priyadharshi Praharaj, Tapas K Maiti, Sujit K Bhutia
PUMA, a BH3-only pro-apoptotic Bcl2 family protein, is known to translocate from the cytosol into the mitochondria in order to induce apoptosis. Interestingly, the induction of PUMA by p53 plays a critical role in DNA damage-induced apoptosis. In this study, we report mitophagy inducing potential of PUMA triggered by phytolectin Abrus agglutinin (AGG) in U87MG glioblastoma cells and established AGG-induced ceramide acts as the chief mediator of mitophagy dependent cell death through activation of both mitochondrial ROS as well as ER stress...
December 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29225136/in-vitro-apoptotic-mechanism-of-a-novel-synthetic-quinazolinyl-derivative-induces-caspase-dependent-intrinsic-pathway-on-thp-1-leukemia-cell-line
#17
V Sridhar, S K Arepalli, L R Velatooru, J Venkateswara Rao, P Kavin Kennedy, B Narsaiah
Several quinazoline derivatives have been found to possess a broad spectrum of biological activities. Previously our research group has synthesized and studied the anti-proliferative effects of N-Decyl-N-(2-Methyl-4-Quinazolinyl) Amine (DMQA). The current study evaluated the cytotoxic and apoptotic properties of DMQA in THP-1 cells. The cytotoxic potential of DMQA was assessed using MTT assay on a panel of cancer cell lines which include HeLa, Mia PaCa-2, A 375, B16-F10, A 549,A 431, U937, THP-1, HL-60 and peripheral blood mononuclear cells (PBMC's)...
December 7, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29225034/cytosolic-iron-sulfur-assembly-is-evolutionarily-tuned-by-a-cancer-amplified-ubiquitin-ligase
#18
Jenny L Weon, Seung Wook Yang, Patrick Ryan Potts
The cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) pathway functions to incorporate inorganic Fe-S cofactors into a variety of proteins, including several DNA repair enzymes. However, the mechanisms regulating the CIA pathway are unknown. We describe here that the MAGE-F1-NSE1 E3 ubiquitin ligase regulates the CIA pathway through ubiquitination and degradation of the CIA-targeting protein MMS19. Overexpression or knockout of MAGE-F1 altered Fe-S incorporation into MMS19-dependent DNA repair enzymes, DNA repair capacity, sensitivity to DNA-damaging agents, and iron homeostasis...
November 30, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29217266/auriculasin-induced-ros-causes-prostate-cancer-cell-death-via-induction-of-apoptosis
#19
Hyun-Dong Cho, Ju-Hye Lee, Kwang-Deog Moon, Ki-Hun Park, Mi-Kyung Lee, Kwon-Il Seo
Recent studies have demonstrated that natural agents targeting the accumulation of reactive oxygen species (ROS) that selectively kill, leaving normal cells undamaged, can suppress prostate cancer. Here, we show that auriculasin, derived from Flemingia philippinensis, induces significant cell death and apoptosis via ROS generation in prostate cancer cells. Auriculasin treatment resulted in selective apoptotic cell death in LNCaP prostate cancer cells, characterized by DNA fragmentation, accumulation of sub-G1 cell population, cleavage of poly (ADP-ribose) polymerase (PARP), regulation of Bax/Bcl-2 ratio, increase of cytosolic apoptosis-inducing factor (AIF) and endonuclease G (EndoG), in addition to inhibiting tumor growth in a xenograft mouse model...
December 4, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29215161/suppressive-oligodeoxynucleotides-containing-ttaggg-motifs-inhibit-cgas-activation-in-human-monocytes
#20
Folkert Steinhagen, Thomas Zillinger, Konrad Peukert, Mario Fox, Marcus Thudium, Winfried Barchet, Christian Putensen, Dennis Klinman, Eicke Latz, Christian Bode
Type I interferon (IFN) is a critical mediator of autoimmune diseases such as systemic lupus erythematosus (SLE) and Aicardi-Goutières Syndrome (AGS). The recently discovered cyclic-GMP-AMP (cGAMP) synthase (cGAS) induces the production of type I IFN in response to cytosolic DNA and is potentially linked to SLE and AGS. Suppressive oligodeoxynucleotides (ODN) containing repetitive TTAGGG motifs present in mammalian telomeres have proven useful in the treatment of autoimmune diseases including SLE. In this study, we demonstrate that the suppressive ODN A151 effectively inhibits activation of cGAS in response to cytosolic DNA, thereby inhibiting type I IFN production by human monocytes...
December 7, 2017: European Journal of Immunology
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