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https://www.readbyqxmd.com/read/29345000/cell-death-under-epithelial-mesenchymal-transition-control-in-prostate-cancer-therapeutic-response
#1
REVIEW
Diane Begemann, Harry Anastos, Natasha Kyprianou
Prostate cancer is a widespread problem among men, with >160 000 new cases in 2017 alone. Androgen deprivation therapy is commonly used in prostate cancer treatment to block androgens required for cancer growth, but disease relapse after androgen deprivation therapy is both common and severe. Changes in androgen receptor signaling from androgen deprivation therapy have been linked to therapeutic resistance and tumor progression. Resistant cells can become reprogrammed to undergo epithelial-mesenchymal transition, a phenotypic switch from benign, epithelial cells to a mobile cell with mesenchymal traits...
January 17, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/29320578/the-potent-effect-of-mycolactone-on-lipid-membranes
#2
Milène Nitenberg, Anaïs Bénarouche, Ofelia Maniti, Estelle Marion, Laurent Marsollier, Julie Géan, Erick J Dufourc, Jean-François Cavalier, Stéphane Canaan, Agnès P Girard-Egrot
Mycolactone is a lipid-like endotoxin synthesized by an environmental human pathogen, Mycobacterium ulcerans, the causal agent of Buruli ulcer disease. Mycolactone has pleiotropic effects on fundamental cellular processes (cell adhesion, cell death and inflammation). Various cellular targets of mycolactone have been identified and a literature survey revealed that most of these targets are membrane receptors residing in ordered plasma membrane nanodomains, within which their functionalities can be modulated...
January 10, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29315934/effect-of-euk-134-on-akt-mtor-signaling-in-the-rat-soleus-during-7-days-of-mechanical-unloading
#3
J Matthew Kuczmarski, Jeff M Hord, Yang Lee, Vinicius Guzzoni, Dinah Rodriguez, Matthew S Lawler, Erika L Garcia-Villatoro, Dylan Holly, Patrick Ryan, Kristian Falcon, Marcela Garcia, Mariana Janini Gomes, James D Fluckey, John M Lawler
Mechanical unloading stimulates rapid changes in skeletal muscle morphology, characterized by atrophy of muscle fiber cross-sectional area (CSA) and a partial fiber-type shift from slow to fast-twitch. Recent studies revealed that oxidative stress contributes to activation of FoxO3a, proteolytic signaling and unloading-induced muscle atrophy via translocation of the mu-splice variant of neuronal nitric oxide synthase (nNOSμ) and activation of FoxO3a. Yet, there is limited understanding of the role of reactive oxygen species (ROS) on the Akt-mTOR pathway signaling during unloading...
January 8, 2018: Experimental Physiology
https://www.readbyqxmd.com/read/29290039/evidence-of-g-protein-coupled-receptor-and-substrate-transporter-heteromerization-at-a-single-molecule-level
#4
Jana Fischer, Gunnar Kleinau, Claudia Rutz, Denise Zwanziger, Noushafarin Khajavi, Anne Müller, Maren Rehders, Klaudia Brix, Catherine L Worth, Dagmar Führer, Heiko Krude, Burkhard Wiesner, Ralf Schülein, Heike Biebermann
G-protein-coupled receptors (GPCRs) can constitute complexes with non-GPCR integral membrane proteins, while such interaction has not been demonstrated at a single molecule level so far. We here investigated the potential interaction between the thyrotropin receptor (TSHR) and the monocarboxylate transporter 8 (MCT8), a member of the major facilitator superfamily (MFS), using fluorescence cross-correlation spectroscopy (FCCS). Both the proteins are expressed endogenously on the basolateral plasma membrane of the thyrocytes and are involved in stimulation of thyroid hormone production and release...
December 30, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29284965/immunohistochemical-expression-of-ezrin-in-oral-potentially-malignant-disorders-a-descriptive-study
#5
Raghini Mohanraj, Pratibha Ramani, Priya Premkumar, Anuja Natesan, Herald J Sherlin, Gheena Sukumaran
Introduction: Ezrin, also known as cytovillin, is a member of the ERM family of protein. Ezrin cross-links actin filament with the plasma membrane. They are involved in the formation of microvilli, cell-cell adhesion, maintenance of cell shape, cell motility, and membrane trafficking. Recent analysis reveals their involvement in signaling pathways. Ezrin is highly expressed in several types of human cancers, and correlation between its immunoreactivity and histopathological data as well as the patient outcome has previously been studied...
November 2017: Journal of Pharmacy & Bioallied Sciences
https://www.readbyqxmd.com/read/29281667/urothelial-maxik-activity-regulates-mucosal-and-detrusor-metabolism
#6
Yi Wang, Gary G Deng, Kelvin P Davies
There is increasing evidence for a role of MaxiK potassium channel-activity in regulating the metabolism and intracellular signaling of non-contractile bladder mucosal tissues. At present however no studies have determined the impact of urothelial MaxiK-activity on overall bladder metabolism. To address this we have investigated the effect of bladder lumen instillation of the MaxiK inhibitor, iberiotoxin (IBTX), on mucosal and detrusor metabolism using metabolomics. Since IBTX does not cross plasma membranes, when instilled into the bladder lumen it would only effect urothelially expressed MaxiK-activity...
2017: PloS One
https://www.readbyqxmd.com/read/29274244/intracellular-potassium-under-osmotic-stress-determines-the-dielectrophoresis-cross-over-frequency-of-murine-myeloma-cells-in-the-mhz-range
#7
Colin Chung, Ronald Pethig, Stewart Smith, Martin Waterfall
Dielectrophoresis (DEP) has been widely studied for its potential as a biomarker-free method of sorting and characterizing cells based upon their dielectric properties. Most studies have employed voltage signals from ∼1 kHz to no higher than ∼30 MHz. Within this range a transition from negative to positive DEP can be observed at the cross-over frequency fx01 . The value of fx01 is determined by the conductivity of the suspending medium, as well as the size and shape of the cell and the dielectric properties (capacitance, conductivity) of its plasma membrane...
December 23, 2017: Electrophoresis
https://www.readbyqxmd.com/read/29273632/oncogenic-ras-isoforms-signaling-specificity-at-the-membrane
#8
REVIEW
Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang
How do Ras isoforms attain oncogenic specificity at the membrane? Oncogenic KRas, HRas, and NRas (K-Ras, H-Ras, and N-Ras) differentially populate distinct cancers. How they selectively activate effectors and why is KRas4B the most prevalent are highly significant questions. Here, we consider determinants that may bias isoform-specific effector activation and signaling at the membrane. We merge functional data with a conformational view to provide mechanistic insight. Cell-specific expression levels, pathway cross-talk, and distinct interactions are the key, but conformational trends can modulate selectivity...
December 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/29262362/interaction-of-monomeric-interleukin-8-with-cxcr1-mapped-by-proton-detected-fast-mas-solid-state%C3%A2-nmr
#9
Sang Ho Park, Sabrina Berkamp, Jasmina Radoicic, Anna A De Angelis, Stanley J Opella
The human chemokine interleukin-8 (IL-8; CXCL8) is a key mediator of innate immune and inflammatory responses. This small, soluble protein triggers a host of biological effects upon binding and activating CXCR1, a G protein-coupled receptor, located in the cell membrane of neutrophils. Here, we describe 1H-detected magic angle spinning solid-state NMR studies of monomeric IL-8 (1-66) bound to full-length and truncated constructs of CXCR1 in phospholipid bilayers under physiological conditions. Cross-polarization experiments demonstrate that most backbone amide sites of IL-8 (1-66) are immobilized and that their chemical shifts are perturbed upon binding to CXCR1, demonstrating that the dynamics and environments of chemokine residues are affected by interactions with the chemokine receptor...
December 19, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29262359/a-hinged-signal-peptide-hairpin-enables-tat-dependent-protein-translocation
#10
Shruthi Hamsanathan, Tamil S Anthonymuthu, Umesh K Bageshwar, Siegfried M Musser
The Tat machinery catalyzes the transport of folded proteins across the bacterial cytoplasmic membrane and the thylakoid membrane in plants. Using fluorescence quenching and cross-linking approaches, we demonstrate that the Escherichia coli TatBC complex catalyzes insertion of a pre-SufI signal peptide hairpin that penetrates about halfway across the membrane bilayer. Analysis of 512 bacterial Tat signal peptides using secondary structure prediction and docking algorithms suggest that this hairpin interaction mode is generally conserved...
December 19, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29259621/the-age-rage-axis-implications-for-age-associated-arterial-diseases
#11
REVIEW
Laura M Senatus, Ann Marie Schmidt
The process of advanced glycation leads to the generation and accumulation of an heterogeneous class of molecules called advanced glycation endproducts, or AGEs. AGEs are produced to accelerated degrees in disorders such as diabetes, renal failure, inflammation, neurodegeneration, and in aging. Further, AGEs are present in foods and in tobacco products. Hence, through both endogenous production and exogenous consumption, AGEs perturb vascular homeostasis by a number of means; in the first case, AGEs can cause cross-linking of long-lived molecules in the basement membranes such as collagens, thereby leading to "vascular stiffening" and processes that lead to hyperpermeability and loss of structural integrity...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/29249810/schizophrenia-and-depression-two-poles-of-endocannabinoid-system-deregulation
#12
María Rodríguez-Muñoz, Pilar Sánchez-Blázquez, Luis F Callado, J Javier Meana, Javier Garzón-Niño
The activity of certain G protein-coupled receptors (GPCRs) and of glutamate N-Methyl-D-aspartate receptors (NMDARs) is altered in both schizophrenia and depression. Using postmortem prefrontal cortex samples from subjects with schizophrenia or depression, we observed a series of opposite changes in the expression of signaling proteins that have been implicated in the cross-talk between GPCRs and NMDARs. Thus, the levels of HINT1 proteins and NMDAR NR1 subunits carrying the C1 cytosolic segment were increased in depressives and decreased in schizophrenics, respect to matched controls...
December 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29248956/human-c-src-kinase-csk-overexpression-makes-t-cells-dummy
#13
Else Marit Inderberg, Nadia Mensali, Morten P Oksvold, Lars-Egil Fallang, Anne Fåne, Gjertrud Skorstad, Grethe-Elisabeth Stenvik, Cinzia Progida, Oddmund Bakke, Gunnar Kvalheim, June H Myklebust, Sébastien Wälchli
Adoptive cell therapy with T-cell receptor (TCR)-engineered T cells represents a powerful method to redirect the immune system against tumours. However, although TCR recognition is restricted to a specific peptide-MHC (pMHC) complex, increasing numbers of reports have shown cross-reactivity and off-target effects with severe consequences for the patients. This demands further development of strategies to validate TCR safety prior to clinical use. We reasoned that the desired TCR signalling depends on correct pMHC recognition on the outside and a restricted clustering on the inside of the cell...
December 16, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29248464/decanoic-acid-suppresses-proliferation-and-invasiveness-of-human-trophoblast-cells-by-disrupting-mitochondrial-function
#14
Changwon Yang, Whasun Lim, Fuller W Bazer, Gwonhwa Song
Decanoic acid (DA) is a medium-chain fatty acid used in the manufacture of various products including plastics, cosmetics, and lubricants. In addition to antiviral and antibacterial effects, DA's, reported biological activities include regulation of signaling pathways and redox homeostasis in various human cell types. The influence of DA on functional properties of human trophoblasts, including proliferation, invasion and apoptosis is currently unknown. In the present study, we evaluated the anti-proliferative and anti-invasive effects of DA on the human trophoblast cell line HTR8/SVneo...
December 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29247050/voltage-modulates-halothane-triggered-ca2-release-in-malignant-hyperthermia-susceptible-muscle
#15
Alberto Zullo, Martin Textor, Philipp Elischer, Stefan Mall, Andreas Alt, Werner Klingler, Werner Melzer
Malignant hyperthermia (MH) is a fatal hypermetabolic state that may occur during general anesthesia in susceptible individuals. It is often caused by mutations in the ryanodine receptor RyR1 that favor drug-induced release of Ca2+ from the sarcoplasmic reticulum. Here, knowing that membrane depolarization triggers Ca2+ release in normal muscle function, we study the cross-influence of membrane potential and anesthetic drugs on Ca2+ release. We used short single muscle fibers of knock-in mice heterozygous for the RyR1 mutation Y524S combined with microfluorimetry to measure intracellular Ca2+ signals...
December 15, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29237464/tlr3-promotes-mmp-9-production-in-primary-human-airway-epithelial-cells-through-wnt-%C3%AE-catenin-signaling
#16
P-J Royer, K Henrio, M Pain, J Loy, A Roux, A Tissot, P Lacoste, C Pison, S Brouard, A Magnan
BACKGROUND: Airway epithelial cells (AEC) act as the first line of defence in case of lung infections. They constitute a physical barrier against pathogens and they participate in the initiation of the immune response. Yet, the modalities of pathogen recognition by AEC and the consequences on the epithelial barrier remain poorly documented. METHOD: We investigated the response of primary human AEC to viral (polyinosinic-polycytidylic acid, poly(I:C)) and bacterial (lipopolysaccharide, LPS) stimulations in combination with the lung remodeling factor Transforming Growth Factor-β (TGF-β)...
December 13, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29222109/marcks-related-protein-regulates-cytoskeletal-organization-at-cell-cell-and-cell-substrate-contacts-in-epithelial-cells
#17
Christina M Van Itallie, Amber Jean Tietgens, Angel Aponte, Marjan Gucek, Alexander X Cartagena-Rivera, Richard S Chadwick, James M Anderson
MARCKS-related protein (MRP) is tagged by biotin ligase fused to occludin and the level of tagging increases ∼20-fold following IFN/TNF treatment. GFP-MRP is focused at the lateral cell membrane and its overexpression potentiates the physiological response of the tight junction barrier to cytokines. However, deletion of MRP does not abrogate cytokine responses, suggesting that MRP is not required in the occludin-dependent IFN/TNF response. Instead, our results reveal a key role for MRP in epithelial cells in control of multiple actin-based structures, likely by regulation of integrin signaling...
December 8, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29210641/dynamic-localization-of-hepatocellular-transporters-role-in-biliary-excretion-and-impairment-in-cholestasis
#18
Marcelo Gabriel Roma, Ismael R Barosso, Gisel S Miszczuk, Fernando A Crocenzi, Enrique J Sanchez Pozzi
Bile flow generation is driven by the vectorial transfer of osmotically active compounds from sinusoidal blood into a confined space, the bile canaliculus. Hence, localization of hepatocellular transporters relevant to bile formation is crucial for bile secretion. Hepatocellular transporters are localized either in the plasma membrane or in recycling endosomes, from where they can be relocated to the plasma membrane on demand, or endocytosed when the demand decreases. The balance between endocytic internalization/exocytic targeting to/from this recycling compartment is therefore the main determinant of the hepatic capability to generate bile, and to dispose endo- and xenobiotics...
December 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29198894/design-synthesis-and-biological-evaluation-of-novel-indole-xanthendione-hybrids-as-selective-estrogen-receptor-modulators
#19
Ramit Singla, Kunj Bihari Gupta, Shishir Upadhyay, Monisha Dhiman, Vikas Jaitak
Ground breaking clinical therapeutic advances in the treatment of breast cancer (BC) is the introduction of selective estrogen receptor modulators (SERMs). We have expeditiously designed and synthesized indole-xanthendione hybrids by coalescing the indole nucleus with xanthendione. All the compounds were first screened for anti-proliferative activity, cytotoxicity and ER-α binding affinity by utilizing ER-α dominant T47D BC cell lines, PBMCs and ER-α competitor assay kit. From this study, two representative compounds 6e and 6f showing most promising activity were advanced for gene expression studies for targeting ER-α...
November 30, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29182711/evaluation-of-the-neuroprotective-potential-of-n-acetylcysteine-for-prevention-and-treatment-of-cognitive-aging-and-dementia
#20
Y Hara, N McKeehan, P A Dacks, H M Fillit
Alzheimer's disease is a progressive neurodegenerative disease for which there is no cure and only a few treatments providing little relief. Increased oxidative stress that is associated with aging is strongly implicated in the pathogenesis and progression of Alzheimer's disease. Studies have shown that levels of the endogenous antioxidant glutathione decline at an early stage of Alzheimer's disease with decreased levels correlating with worse cognitive functions. N-acetylcysteine, a drug also widely available as a dietary supplement, is a precursor of L-cysteine, which in turn is a component of glutathione...
2017: Journal of Prevention of Alzheimer's Disease
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