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https://www.readbyqxmd.com/read/27906112/chromatin-wide-and-transcriptome-profiling-integration-uncovers-p38%C3%AE-mapk-as-a-global-regulator-of-skeletal-muscle-differentiation
#1
Jessica Segalés, Abul B M M K Islam, Roshan Kumar, Qi-Cai Liu, Pedro Sousa-Victor, F Jeffrey Dilworth, Esteban Ballestar, Eusebio Perdiguero, Pura Muñoz-Cánoves
BACKGROUND: Extracellular stimuli induce gene expression responses through intracellular signaling mediators. The p38 signaling pathway is a paradigm of the mitogen-activated protein kinase (MAPK) family that, although originally identified as stress-response mediator, contributes to establishing stem cell differentiation fates. p38α is central for induction of the differentiation fate of the skeletal muscle stem cells (satellite cells) through not fully characterized mechanisms. METHODS: To investigate the global gene transcription program regulated by p38α during satellite cell differentiation (myogenesis), and to specifically address whether this regulation occurs through direct action of p38α on gene promoters, we performed a combination of microarray gene expression and genome-wide binding analyses...
March 15, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906063/characterization-of-a-multiprotein-complex-involved-in-excitation-transcription-coupling-of-skeletal-muscle
#2
Manuel Arias-Calderón, Gonzalo Almarza, Alexis Díaz-Vegas, Ariel Contreras-Ferrat, Denisse Valladares, Mariana Casas, Héctor Toledo, Enrique Jaimovich, Sonja Buvinic
BACKGROUND: Electrical activity regulates the expression of skeletal muscle genes by a process known as "excitation-transcription" (E-T) coupling. We have demonstrated that release of adenosine 5'-triphosphate (ATP) during depolarization activates membrane P2X/P2Y receptors, being the fundamental mediators between electrical stimulation, slow intracellular calcium transients, and gene expression. We propose that this signaling pathway would require the proper coordination between the voltage sensor (dihydropyridine receptor, DHPR), pannexin 1 channels (Panx1, ATP release conduit), nucleotide receptors, and other signaling molecules...
April 11, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27905300/intravital-imaging-of-mouse-urothelium-reveals-activation-of-extracellular-signal-regulated-kinase-by-stretch-induced-intravesical-release-of-atp
#3
Takeshi Sano, Takashi Kobayashi, Hiromitsu Negoro, Atsushi Sengiku, Takuya Hiratsuka, Yuji Kamioka, Louis S Liou, Osamu Ogawa, Michiyuki Matsuda
To better understand the roles played by signaling molecules in the bladder, we established a protocol of intravital imaging of the bladder of mice expressing a Förster/fluorescence resonance energy transfer (FRET) biosensor for extracellular signal-regulated kinase (ERK), which plays critical roles not only in cell growth but also stress responses. With an upright two-photon excitation microscope and a vacuum-stabilized imaging window, cellular ERK activity was visualized in the whole bladder wall, from adventitia to urothelium...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27904901/effect-of-ticagrelor-on-endothelial-calcium-signalling-and-barrier-function
#4
Dursun Gündüz, Christian Tanislav, Klaus-Dieter Schlüter, Rainer Schulz, Christian Hamm, Muhammad Aslam
The P2Y12 receptor is a Gi-coupled receptor whose activation inhibits adenylyl cyclase and thereby reduces the concentration of intracellular cAMP. Here the hypothesis was tested whether AR-C 66096 or ticagrelor, two direct-acting and reversibly binding P2Y12 receptor antagonists, protect endothelial cell (EC) barrier function by raising intracellular cAMP in ECs. The study was carried out on primary human umbilical vein ECs (HUVECs) and human pulmonary microvascular ECs (hPMECs). AR-C66096 (10 µM) induced a 50 % increase in cAMP in ECs whereas ticagrelor (2-10 µM) had no effect...
December 1, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27903965/tumor-associated-mesenchymal-stem-like-cells-provide-extracellular-signaling-cue-for-invasiveness-of-glioblastoma-cells
#5
Eun-Jung Lim, Yongjoon Suh, Ki-Chun Yoo, Ji-Hyun Lee, In-Gyu Kim, Min-Jung Kim, Jong Hee Chang, Seok-Gu Kang, Su-Jae Lee
Hyaluronic acid (HA) is abundant in tumor microenvironment and closely associated with invasiveness of glioblastoma (GBM) cells. However, the cellular mechanism underlying HA-rich microenvironment in GBM remains unexplored. Here, we show that tumor-associated mesenchymal stem-like cells (tMSLCs) contribute to abundance of hyaluronic acid (HA) in tumor microenvironment through HA synthase-2 (HAS2) induction, and thereby enhances invasiveness of GBM cells. In an autocrine manner, C5a secreted by tMSLCs activated ERK MAPK for HAS2 induction in tMSLCs...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902702/selective-inhibitor-of-nuclear-export-sine-compounds-alter-new-world-alphavirus-capsid-localization-and-reduce-viral-replication-in-mammalian-cells
#6
Lindsay Lundberg, Chelsea Pinkham, Cynthia de la Fuente, Ashwini Brahms, Nazly Shafagati, Kylie M Wagstaff, David A Jans, Sharon Tamir, Kylene Kehn-Hall
The capsid structural protein of the New World alphavirus, Venezuelan equine encephalitis virus (VEEV), interacts with the host nuclear transport proteins importin α/β1 and CRM1. Novel selective inhibitor of nuclear export (SINE) compounds, KPT-185, KPT-335 (verdinexor), and KPT-350, target the host's primary nuclear export protein, CRM1, in a manner similar to the archetypical inhibitor Leptomycin B. One major limitation of Leptomycin B is its irreversible binding to CRM1; which SINE compounds alleviate because they are slowly reversible...
November 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27902413/methanosarcina-acetivorans-utilizes-a-single-nadph-dependent-thioredoxin-system-and-contains-additional-thioredoxin-homologs-with-distinct-functions
#7
Addison C McCarver, Faith H Lessner, Jose M Soroeta, Daniel J Lessner
The thioredoxin system plays a central role in the intracellular redox maintenance in the majority of cells. The canonical system is comprised of an NADPH-dependent thioredoxin reductase (TrxR) that reduces the disulfide reductase thioredoxin (Trx). Although Trx is encoded in almost all sequenced genomes of methanogens, its incorporation into their unique physiology is not well understood. Methanosarcina acetivorans contains a single TrxR (MaTrxR) and seven Trx (MaTrx1-7) homologs. We previously showed that MaTrxR and at least MaTrx7 comprise a functional NADPH-dependent thioredoxin system...
November 29, 2016: Microbiology
https://www.readbyqxmd.com/read/27899617/epigenetic-and-genetic-deregulation-in-cancer-target-distinct-signaling-pathway-domains
#8
Yang Gao, Andrew E Teschendorff
Cancer is characterized by both genetic and epigenetic alterations. While cancer driver mutations and copy-number alterations have been studied at a systems-level, relatively little is known about the systems-level patterns exhibited by their epigenetic counterparts. Here we perform a pan-cancer wide systems-level analysis, mapping candidate cancer-driver DNA methylation (DNAm) alterations onto a human interactome. We demonstrate that functional DNAm alterations in cancer tend to map to nodes of lower connectivity and inter-connectivity, compared to the corresponding alterations at the genomic level...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899395/functional-definition-of-progenitors-versus-mature-endothelial-cells-reveals-key-soxf-dependent-differentiation-process
#9
Jatin Patel, Elke J Seppanen, Mathieu P Rodero, Ho Yi Wong, Prudence Donovan, Zoltan Neufeld, Nicholas M Fisk, Mathias François, Kiarash Khosrotehrani
BACKGROUND: -During adult life, blood vessel formation is thought to occur via angiogenic processes involving branching from existing vessels. An alternate proposal suggests that neo-vessels form from endothelial progenitors able to assemble the intimal layers. We here aimed to define vessel-resident endothelial progenitors in vivo in a variety of tissues in physiological and pathological situations such as normal aorta, lungs, as well as wound healing, tumors and placenta. METHODS: -Based on protein expression levels of common endothelial markers using flow cytometry, three sub-populations of endothelial cells could be identified among VE-Cadherin+ and CD45- cells...
November 29, 2016: Circulation
https://www.readbyqxmd.com/read/27897204/human-mitochondrial-transcriptional-factor-a-breaks-the-mitochondria-mediated-vicious-cycle-in-alzheimer-s-disease
#10
Sugako Oka, Julio Leon, Kunihiko Sakumi, Tomomi Ide, Dongchon Kang, Frank M LaFerla, Yusaku Nakabeppu
In the mitochondria-mediated vicious cycle of Alzheimer's disease (AD), intracellular amyloid β (Aβ) induces mitochondrial dysfunction and reactive oxygen species, which further accelerate Aβ accumulation. This vicious cycle is thought to play a pivotal role in the development of AD, although the molecular mechanism remains unclear. Here, we examined the effects of human mitochondrial transcriptional factor A (hTFAM) on the pathology of a mouse model of AD (3xTg-AD), because TFAM is known to protect mitochondria from oxidative stress through maintenance of mitochondrial DNA (mtDNA)...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27896916/dihydroartemisinin-counteracts-fibrotic-portal-hypertension-via-farnesoid-x-receptor-dependent-inhibition-of-hepatic-stellate-cell-contraction
#11
Wenxuan Xu, Chunfeng Lu, Feng Zhang, Jiangjuan Shao, Shunyu Yao, Shizhong Zheng
Portal hypertension is a frequent pathological symptom occurring especially in hepatic fibrosis and cirrhosis. Current paradigms indicate that inhibition of hepatic stellate cell (HSC) activation and contraction is anticipated to be an attractive therapeutic strategy, because activated HSC dominantly facilitates an increase in intrahepatic vein pressure through secreting extracellular matrix and contracting. Our previous in vitro study indicated that dihydroartemisinin (DHA) inhibited contractility of cultured HSC by activating intracellular farnesoid X receptor (FXR)...
November 7, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27896810/multiple-pathways-for-elevating-extracellular-adenosine-in-the-rat-hippocampal-ca1-region-characterized-by-adenosine-sensor-cells
#12
Kunihiko Yamashiro, Yuki Fujii, Shohei Maekawa, Mitsuhiro Morita
Extracellular adenosine in the brain, which modulates various physiological and pathological processes, fluctuates in a complicated manner that reflects the circadian cycle, neuronal activity, metabolism, and disease states. The dynamics of extracellular adenosine in the brain are not fully understood, largely because of the lack of simple and reliable methods of measuring time-dependent changes in tissue adenosine distribution. This study describes the development of a biosensor, designated an adenosine sensor cell, expressing adenosine A1 receptor, and a genetically modified G protein...
November 5, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27894810/na-ca-2-exchanger-1-inhibition-abolishes-ischemic-tolerance-induced-by-ischemic-preconditioning-in-different-cardiac-models
#13
Pasqualina Castaldo, Maria Loredana Macrì, Vincenzo Lariccia, Alessandra Matteucci, Marta Maiolino, Santo Gratteri, Salvatore Amoroso, Simona Magi
Ca(2+)-handling disturbances play an important role in the genesis of myocardial ischemia/reperfusion (I/R) injury. Ischemic preconditioning (IPC) is a powerful strategy to induce tolerance against subsequent ischemic episodes. IPC signaling pathways may be triggered by Ca(2+) ion. Since Na(+)/Ca(2+) exchanger 1 (NCX1) participates in modulating intracellular Ca(2+) homeostasis, here we further defined its role in I/R and investigated its potential involvement in IPC-induced cardioprotection. In isolated ventricular cardiomyocytes, perfused rat heart and H9c2 cardiomyoblasts, I/R produceda significant cellinjury, assessed by measuring extracellular lactate dehydrogenase (LDH) and, for the whole heart, also by estimating myocardialinfarct size area...
November 25, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27893705/gephyrin-binding-peptides-visualize-postsynaptic-sites-and-modulate-neurotransmission
#14
Hans Michael Maric, Torben Johann Hausrat, Franziska Neubert, Nils Ole Dalby, Sören Doose, Markus Sauer, Matthias Kneussel, Kristian Strømgaard
γ-Aminobutyric acid type A and glycine receptors are the major mediators of fast synaptic inhibition in the human central nervous system and are established drug targets. However, all drugs targeting these receptors bind to the extracellular ligand-binding domain of the receptors, which inherently is associated with perturbation of the basic physiological action. Here we pursue a fundamentally different approach, by instead targeting the intracellular receptor-gephyrin interaction. First, we defined the gephyrin peptide-binding consensus sequence, which facilitated the development of gephyrin super-binding peptides and later effective affinity probes for the isolation of native gephyrin...
November 28, 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27892528/sphingomyelin-generated-by-sphingomyelin-synthase-1-is-involved-in-attachment-and-infection-with-japanese-encephalitis-virus
#15
Makoto Taniguchi, Takafumi Tasaki, Hideaki Ninomiya, Yoshibumi Ueda, Koh-Ichi Kuremoto, Susumu Mitsutake, Yasuyuki Igarashi, Toshiro Okazaki, Tsutomu Takegami
Japanese encephalitis virus (JEV) is a mosquito-borne RNA virus which infects target cells via the envelope protein JEV-E. However, its cellular targets are largely unknown. To investigate the role of sphingomyelin (SM) in JEV infection, we utilized SM-deficient immortalized mouse embryonic fibroblasts (tMEF) established from SM synthase 1 (SMS1)/SMS2 double knockout mice. SMS deficiency significantly reduced both intracellular and extracellular JEV levels at 48 h after infection. Furthermore, after 15 min treatment with JEV, the early steps of JEV infection such as attachment and cell entry were also diminished in SMS-deficient tMEFs...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27891582/versatile-roles-of-intracellularly-located-trpv1-channel
#16
REVIEW
Rui Zhao, Suk Ying Tsang
The ubiquitous expression in many organs throughout the body and the ability to respond to a wide variety of physical and chemical stimuli have brought transient receptor potential (TRP) channels to the vanguards of our sensory systems. TRP vanilloid-1 (TRPV1) is the founding member of the TRPV subfamily. TRPV1 can be activated by noxious heat, protons and vanilloids. Previous studies have shown that TRPV1 is located on the plasma membrane, serving to non-selectively permeate calcium ion from the extracellular region to the cytoplasm...
November 27, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27891500/interspecies-communication-between-pathogens-and-immune-cells-via-bacterial-membrane-vesicles
#17
Katerina S Jurkoshek, Ying Wang, Jaffre J Athman, Marian R Barton, Pamela A Wearsch
The production of extracellular vesicles is a universal mechanism for intercellular communication that is conserved across kingdoms. Prokaryotes secrete 50-250 nm membrane vesicles (MVs) in a manner that is regulated by environmental stress and is thought to promote survival. Since many types of host-derived stress are encountered during infection, this implies an important role for MV secretion in bacterial pathogenesis. Accordingly, MVs produced by gram-positive and gram-negative pathogens contain toxins, virulence factors, and other molecules that promote survival in the host...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27889088/osteoblast-cellular-activity-on-low-elastic-modulus-ti-24nb-4zr-8sn-alloy
#18
K C Nune, R D K Misra, S J Li, Y L Hao, R Yang
OBJECTIVES: Low modulus β-titanium alloys with non-toxic alloying elements are envisaged to provide good biocompatibility and alleviate the undesired stress shielding effect. The objective of this study is to fundamentally elucidate the biological response of novel high strength-low elastic modulus Ti2448 alloy through the study of bioactivity and osteoblast cell functions. METHODS: Characterization techniques such as SEM, EDX, XRD, and fluorescence microscopy were utilized to analyze the microstructure, morphology, chemical composition, and cell adhesion...
November 23, 2016: Dental Materials: Official Publication of the Academy of Dental Materials
https://www.readbyqxmd.com/read/27888137/the-role-of-rhoa-in-retrograde-neuronal-death-and-axon-regeneration-after-spinal-cord-injury
#19
Jianli Hu, Guixin Zhang, William Rodemer, Li-Qing Jin, Michael Shifman, Michael E Selzer
Paralysis following spinal cord injury (SCI) is due to interruption of axons and their failure to regenerate. It has been suggested that the small GTPase RhoA may be an intracellular signaling convergence point for several types of growth-inhibiting extracellular molecules. Even if this is true in vitro, it is not clear from studies in mammalian SCI, whether the effects of RhoA manipulations on axon growth in vivo are due to a RhoA-mediated inhibition of true regeneration or only of collateral sprouting from spared axons, since work on SCI generally is performed with partial injury models...
November 22, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27886639/hyaluronan-derived-swelling-of-solid-tumors-the-contribution-of-collagen-and-cancer-cells-and-implications-for-cancer-therapy
#20
Chrysovalantis Voutouri, Christiana Polydorou, Panagiotis Papageorgis, Vasiliki Gkretsi, Triantafyllos Stylianopoulos
Despite the important role that mechanical forces play in tumor growth and therapy, the contribution of swelling to tumor mechanopathology remains unexplored. Tumors rich in hyaluronan exhibit a highly negative fixed charge density. Repulsive forces among these negative charges as well as swelling of cancer cells due to regulation of intracellular tonicity can cause tumor swelling and development of stress that might compress blood vessels, compromising tumor perfusion and drug delivery. Here, we designed an experimental strategy, using four orthotopic tumor models, to measure swelling stress and related swelling to extracellular matrix components, hyaluronan and collagen, as well as to tumor perfusion...
November 21, 2016: Neoplasia: An International Journal for Oncology Research
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