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https://www.readbyqxmd.com/read/28636317/downsizing-proto-oncogene-cfos-to-short-helix-constrained-peptides-that-bind-jun
#1
Daniel Baxter, Samuel R Perry, Timothy A Hill, W Mei Kok, Nathan R Zaccai, R Leo Brady, David P Fairlie, Jody M Mason
The oncogenic transcription factor activator protein-1 (AP-1) is a DNA-binding protein that assembles through dimerization of Fos and Jun protein subunits, their leucine-rich helical sequences entwining into a coiled-coil structure. This study reports on downsizing the proto-oncogene cFos protein (380 residues) to shorter peptides (37-25 residues) modified with helix-inducing constraints to enhance binding to Jun. A crystal structure is reported for a 37-residue Fos-derived peptide (FosW) bound to Jun. This guided iterative downsizing of FosW to shorter peptide sequences that were constrained into stable water-soluble α-helices by connecting amino acid side chains to form cyclic pentapeptide components...
June 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28630090/t-cell-transcriptomes-from-paroxysmal-nocturnal-hemoglobinuria-patients-reveal-novel-signaling-pathways
#2
Kohei Hosokawa, Sachiko Kajigaya, Keyvan Keyvanfar, Wangmin Qiao, Yanling Xie, Danielle M Townsley, Xingmin Feng, Neal S Young
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder originating from hematopoietic stem cells and is a life-threating disease characterized by intravascular hemolysis, bone marrow (BM) failure, and venous thrombosis. The etiology of PNH is a somatic mutation in the phosphatidylinositol glycan class A gene (PIG-A) on the X chromosome, which blocks synthesis of the glycolipid moiety and causes deficiency in GPI-anchored proteins. PNH is closely related to aplastic anemia, in which T cells mediate destruction of BM...
June 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28628850/indoline-derivatives-mitigate-liver-damage-in-a-mouse-model-of-acute-liver-injury
#3
Efrat Finkin-Groner, Shlomi Finkin, Shani Zeeli, Marta Weinstock
BACKGROUND: Exposure of mice to D-galactosamine (GalN) and lipopolysaccharide (LPS) induces acute liver failure through elevation of TNF-α, which causes liver damage resembling that in humans. The current study evaluated in this model the effect of two indoline derivatives, which have anti-inflammatory activity in macrophages. METHODS: AN1297 and AN1284 (0.025-0.75mg/kg) or dexamethasone (3mg/kg), were injected subcutaneously, 15min before intraperitoneal injection of GalN (800mg) plus LPS (50μg) in male Balb/C mice...
April 12, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28620810/c-jun-integrates-signals-from-both-mek-erk-and-mkk-jnk-pathways-upon-vaccinia-virus-infection
#4
Flávia G G Leite, Alice A Torres, Leonardo C De Oliveira, André F P Da Cruz, Jamária A P Soares-Martins, Anna C T C Pereira, Giliane S Trindade, Jonatas S Abrahão, Erna G Kroon, Paulo C P Ferreira, Cláudio A Bonjardim
Usurpation of the host's signalling pathways is a common strategy employed by viruses to promote their successful replication. Here we show that infection with the orthopoxvirus vaccinia virus (VACV) leads to sustained stimulation of c-Jun activity during the entire infective cycle. This stimulation is temporally regulated through MEK/ERK or MKK/JNK pathways, i.e. during the early/mid phase (1 to 6 hpi) and in the late phase (9 to 24 hpi) of the infective cycle, respectively. As a transcriptional regulator, upon infection with VACV, c-Jun is translocated from the cytoplasm to the nucleus, where it binds to the AP-1 DNA sequence found at the promoter region of its target genes...
June 15, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28618389/involvement-of-p38-mapk-and-atf-2-signaling-pathway-in-anti-inflammatory-effect-of-a-novel-compound-bis-5-methyl-2-furyl-4-nitrophenyl-methane-on-lipopolysaccharide-stimulated-macrophages
#5
Sarinporn Udompong, Sakulrat Mankhong, Jaray Jaratjaroonphong, Klaokwan Srisook
Activated macrophages produce various pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) and cyclooxygenase (COX)-2-derived prostaglandin E2 (PGE2) during inflammatory response. However, overproduction of NO and PGE2 appears to be involved in pathogenesis of various inflammatory diseases. Therefore, inhibition of NO and PGE2 production might be useful for the treatment of inflammatory-related diseases. In this study, the bis[(5-methyl)2-furyl](4-nitrophenyl)methane or BFNM was evaluated for the anti-inflammatory activity and mechanism of action in lipopolysaccharide (LPS)-stimulated RAW 264...
June 12, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28616865/isoacteoside-a-dihydroxyphenylethyl-glycoside-exhibits-anti-inflammatory-effects-through-blocking-tlr4-dimerization
#6
Hongwei Gao, Yankun Cui, Naixin Kang, Xin Liu, Yanli Liu, Yue Zou, Ziyu Zhang, Xiaoran Li, Shilin Yang, Ji Li, Chunming Wang, Qiong-Ming Xu, Xiuping Chen
BACKGROUND AND PURPOSE: Isoacteoside (ISO) is a phenylethanoid isolated from Monochasma savatieri Franch. ex Maxim., which is an anti-inflammatory herb widely used in traditional Chinese medicine. However, the exact mechanism of the anti-inflammatory activity of ISO is not completely understood. In this study, its anti-inflammatory mechanism in mouse macrophages was elucidated. EXPERIMENTAL APPROACH: The expression of the NF-κB pathway, MAPK pathway, iNOS, TNF-α, IL-6 and IL-1β was evaluated using western blotting, qRT-PCR or ELISA...
June 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28609714/mfhas1-suppresses-tlr4-signaling-pathway-via-induction-of-pp2a-c-subunit-cytoplasm-translocation-and-inhibition-of-c-jun-dephosphorylation-at-thr239
#7
Qiqing Shi, Bo Xiong, Jing Zhong, Huihui Wang, Duan Ma, Changhong Miao
TLR4, an important Toll-like receptor in innate immunity, can be activated by LPS and induce proinflammatory cytokines to resist invasion of pathogenic microorganism, but excessive inflammation can trigger tissue injury. Many genes negatively regulate TLR4 signaling pathway. Recent studies found that malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) suppressed the expression of cytokine IL6 in Raw264.7 cells stimulated by LPS, but the mechanisms remained unclear. This study investigated the role of MFHAS1 in TLR4 signaling pathway and the possible mechanisms implicated...
June 10, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28608695/molecular-elucidation-of-biological-response-to-mesoporous-silica-nanoparticles-in-vitro-and-in-vivo
#8
Cheng-Chung Chou, Wei Chen, Yann Hung, Chung-Yuan Mou
Biomedical applications of mesoporous silica nanoparticles (MSNs) require efficient cellular uptake and low toxicity. The purpose of this study is to investigate the cellular uptake and toxicity of MSNs with different sizes and charges (50, 100 and 250 nm with a positive surface charge and 100 nm with a negative surface charge) exposed to human monocyte-derived macrophages, lung epithelium BEAS-2B cells and mice using genome-wide gene expression analysis and cellular/animal-level end point tests. We found that MSNs can be taken up into cells through endocytosis in a charge- and size-dependent manner, with positively charged and larger MSNs being more easily taken up into the cells by recruiting more types of endocytotic pathways for more cellular uptake...
June 13, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28607484/rare-cell-variability-and-drug-induced-reprogramming-as-a-mode-of-cancer-drug-resistance
#9
Sydney M Shaffer, Margaret C Dunagin, Stefan R Torborg, Eduardo A Torre, Benjamin Emert, Clemens Krepler, Marilda Beqiri, Katrin Sproesser, Patricia A Brafford, Min Xiao, Elliott Eggan, Ioannis N Anastopoulos, Cesar A Vargas-Garcia, Abhyudai Singh, Katherine L Nathanson, Meenhard Herlyn, Arjun Raj
Therapies that target signalling molecules that are mutated in cancers can often have substantial short-term effects, but the emergence of resistant cancer cells is a major barrier to full cures. Resistance can result from secondary mutations, but in other cases there is no clear genetic cause, raising the possibility of non-genetic rare cell variability. Here we show that human melanoma cells can display profound transcriptional variability at the single-cell level that predicts which cells will ultimately resist drug treatment...
June 15, 2017: Nature
https://www.readbyqxmd.com/read/28606801/molecular-cloning-characterization-and-expression-analysis-of-b-cell-lymphoma-2-bcl-2-in-the-orange-spotted-grouper-epinephelus-coioides
#10
Sheng-Wei Luo, Huan Kang, Jing-Rong Kong, Ren-Chong Xie, Yuan Liu, Wei-Na Wang, Fu-Xing Xie, Cong Wang, Zuo-Ming Sun
Bcl-2 is a pro-survival member of Bcl-2 like superfamily, playing an important role in regulating the apoptotic process. In this study, the full-length Bcl-2 (EcBcl-2) was obtained, consisting of a 5'UTR of 290 bp, an ORF of 699 bp and a 3'UTR of 920 bp. EcBcl-2 gene encoded a polypeptide of 232 amino acids with an estimated molecular mass of 26.12 KDa and a predicted isoelectric point (pI) of 6.93. The deduced amino acid sequence analysis showed that EcBcl-2 consisted of the conserved residues and characteristic domains known to the critical functionality for Bcl-2...
June 9, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28602698/early-growth-response-factor-1-is-essential-for-cigarette-smoke-induced-muc5ac-expression-in-human-bronchial-epithelial-cells
#11
Shao-Bin Wang, Chao Zhang, Xu-Chen Xu, Feng Xu, Jie-Sen Zhou, Yan-Ping Wu, Chao Cao, Wen Li, Hua-Hao Shen, Jiao-Fei Cao, Zhi-Hua Chen
Early growth response factor 1 (Egr-1) is a zinc finger transcription factor which responses rapidly to a variety of extracellular stimuli. Previous studies have suggested that Egr-1 exerts pathological functions in chronic obstructive pulmonary disease (COPD) by regulation of cigarette smoking-induced autophagy, cell death, and inflammation. However, little is known about the role of Egr-1 in regulation of mucus production in airway epithelium. In this study, we observed that cigarette smoke extract (CSE) induced a successive expression of Egr-1 and MUC5AC in human bronchial epithelial (HBE) cells...
June 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28602508/cyr61-ccn1-induces-ccl20-production-by-keratinocyte-via-activating-p38-and-jnk-ap-1-pathway-in-psoriasis
#12
Huidan Li, Haichuan Li, Rongfen Huo, Pinru Wu, Zhengyu Shen, Hui Xu, Baihua Shen, Ningli Li
BACKGROUND: Psoriasis is a common chronic skin disease characterized by epidermal hyperplasia and inflammation. Cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) has recently been implicated in psoriasis pathogenesis by promoting keratinocyte activation. However, the mechanisms by which CCN1 enhances cutaneous inflammation are not fully understood. OBJECTIVE: In this study, we investigated the role of CCN1 on the expression of CCL20 in human keratinocyte. METHODS AND RESULTS: By double-label immunofluorescence staining, we first identified that the expression of CCN1 colocalized well with CCL20 production in the epidermis of psoriasis skin lesion...
June 1, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28596505/progressive-modulation-of-the-human-olfactory-bulb-transcriptome-during-alzheimer%C3%A2-s-disease-evolution-novel-insights-into-the-olfactory-signaling-across-proteinopathies
#13
Mercedes Lachen-Montes, María Victoria Zelaya, Víctor Segura, Joaquín Fernández-Irigoyen, Enrique Santamaría
Alzheimer´s disease (AD) is characterized by progressive dementia, initially presenting olfactory dysfunction. Despite the olfactory bulb (OB) is the first central structure of the olfactory pathway, we lack a complete molecular characterization of the transcriptional events that occurs in this olfactory area during AD progression. To address this gap in knowledge, we have assessed the genome-wide expression in postmortem OBs from subjects with varying degree of AD pathology. A stage-dependent deregulation of specific pathways was observed, revealing transmembrane transport, and neuroinflammation as part of the functional modules that are disrupted across AD grading...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28594115/therapeutic-relevance-of-ozone-therapy-in-degenerative-diseases-focus-on-diabetes-and-spinal-pain
#14
REVIEW
Nady Braidy, Morteza Izadi, Antoni Sureda, Nematollah Jonaidi-Jafari, Abdolali Banki, Seyed Fazel Nabavi, Seyed Mohammad Nabavi
Ozone, one of the most important air pollutants, is a triatomic molecule containing three atoms of oxygen that results in an unstable form due to its mesomeric structure. It has been well-known that ozone has potent ability to oxidize organic compounds and can induce respiratory irritation. Although ozone has deleterious effects, many therapeutic effects have also been suggested. Since last decades, the therapeutic potential of ozone has gained much attention through its strong capacity to induce controlled and moderated oxidative stress when administered in precise therapeutic doses...
June 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28593564/activation-of-adrenergic-receptor-in-h9c2-cardiac-myoblasts-co-stimulates-nox2-and-the-derived-ros-mediate-the-downstream-responses
#15
Nikhat Saleem, Shyamal K Goswami
In recent years, NADPH oxidases (Noxes) have emerged as an important player in cardiovascular pathophysiology. Despite the growing evidences on the role of specific Nox isoforms, mechanisms of their activation, targets of reactive oxygen species (ROS) generated, and their downstream effects are poorly understood as yet. In this study, we treated H9c2 cardiac myoblasts with norepinephrine (NE, 2 µM), inducing ROS generation that was inhibited by Nox2-specific peptide inhibitor gp91ds-tat. Organelle-specific hydrogen peroxide-sensitive probe HyPer showed that the site of ROS generation is primarily in the cytosol, to some extent in the endoplasmic reticulum (ER) but not the mitochondria...
June 7, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28593498/bpde-induced-genotoxicity-relationship-between-dna-adducts-mutagenicity-in-the-in-vitro-pig-a-assay-and-the-transcriptional-response-to-dna-damage-in-tk6-cells
#16
Ann Liza Piberger, Christopher T Krüger, Bettina M Strauch, Beatrice Schneider, Andrea Hartwig
Benzo[a]pyrene is a known human carcinogen. As underlying mechanism, the induction of stable DNA adducts and mutations have been repeatedly demonstrated. Also, the activation of cellular stress response on the transcriptional level has been described. Nevertheless, the interrelationship between these different events is less well understood, especially at low, for human exposure relevant concentrations. Within the present study, we applied the reactive metabolite benzo[a]pyrene diolepoxide (BPDE) in the nanomolar, non-cytotoxic concentration range in human TK6 cells and quantified the induction and repair of stable DNA adducts at the N (2)-position of guanine by HPLC with fluorescence detection...
June 7, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28592991/aav-based-dual-reporter-circuit-for-monitoring-cell-signaling-in-living-human-cells
#17
Zhiwen Zhang, Zachary Stickney, Natalie Duong, Kevin Curley, Biao Lu
BACKGROUND: High-throughput methods based on molecular reporters have greatly advanced our knowledge of cell signaling in mammalian cells. However, their ability to monitor various types of cells is markedly limited by the inefficiency of reporter gene delivery. Recombinant adeno-associated virus (AAV) vectors are efficient tools widely used for delivering and expressing transgenes in diverse animal cells in vitro and in vivo. Here we present the design, construction and validation of a novel AAV-based dual-reporter circuit that can be used to monitor and quantify cell signaling in living human cells...
2017: Journal of Biological Engineering
https://www.readbyqxmd.com/read/28591827/tethering-not-required-the-glucocorticoid-receptor-binds-directly-to-activator-protein-1-recognition-motifs-to-repress-inflammatory-genes
#18
Emily R Weikum, Ian Mitchelle S de Vera, Jerome C Nwachukwu, William H Hudson, Kendall W Nettles, Douglas J Kojetin, Eric A Ortlund
The glucocorticoid receptor (GR) is a ligand-regulated transcription factor that controls the expression of extensive gene networks, driving both up- and down-regulation. GR utilizes multiple DNA-binding-dependent and -independent mechanisms to achieve context-specific transcriptional outcomes. The DNA-binding-independent mechanism involves tethering of GR to the pro-inflammatory transcription factor activator protein-1 (AP-1) through protein-protein interactions. This mechanism has served as the predominant model of GR-mediated transrepression of inflammatory genes...
June 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28589371/activator-protein-1-ap-1-a-bridge-between-life-and-death-in-lung-epithelial-a549-cells-under-hypoxia
#19
Seema Yadav, Namita Kalra, Lilly Ganju, Mrinalini Singh
Activator protein-1 (AP-1) transcription factor plays a central role in hypoxia to modulate the expression of genes that decides the fate of the cell. The aim of the present study was to explore the role of AP-1 subunits in lung epithelial (A549) cells under hypoxia. Cell cycle studies by flow cytometry indicated that cell viability was unaffected by the initial hypoxia exposure (0.5% O2 at 37 °C) for 6 and 12 h. However, both transient cell cycle arrest and cell death was detected at 24 and 48 h. Flow cytometry and spectrofluorometry data confirmed the increase in ROS levels...
June 6, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28588678/mechanism-of-n-acetyl-cysteine-inhibition-on-the-cytotoxicity-induced-by-titanium-dioxide-nanoparticles-in-jb6-cells-transfected-with-activator-protein-1
#20
Hongbo Shi, Yuanliang Gu, Zhenhua Xie, Qi Zhou, Guochuan Mao, Xialu Lin, Kui Liu, Yu Liu, Baobo Zou, Jinshun Zhao
The present study investigated the mechanism of N-acetyl-cysteine (NAC) inhibition on the cytotoxicity induced by titanium dioxide (TiO2) nanoparticles (NPs) using murine epidermal JB6 cells transfected with activator protein-1 (AP-1), JB6-AP-1 cells. Confocal microscopy was performed to localize TiO2 NPs in cultured cells. The level of reactive oxygen species (ROS) present in cells was evaluated by staining with 2',7'-dichlorodihydrofluorescein diacetate and dihydroethidium. AP-1 gene expression levels in the cells were detected using the luciferase assay...
June 2017: Experimental and Therapeutic Medicine
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