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https://www.readbyqxmd.com/read/29780533/a-halogen-bond-mediated-highly-active-artificial-chloride-channel-with-high-anticancer-activity
#1
Changliang Ren, Xin Ding, Arundhati Roy, Jie Shen, Shaoyuan Zhou, Feng Chen, Sam Fong Yau Li, Haisheng Ren, Yi Yan Yang, Huaqiang Zeng
Chloride-selective transmembrane carriers or channels might have possible uses in treating channelopathies or cancers. While chloride carriers have been extensively investigated, the corresponding chloride channels have remained limitedly studied. Moreover, all hitherto reported channel systems lack clearly definable and readily modifiable positions in their structures for the reliable construction and combinatorial optimization of their ion transport properties. As a result, the existing channels are limited by their large molecular weight, weak activity or low anion selectivity...
May 7, 2018: Chemical Science
https://www.readbyqxmd.com/read/29772843/the-role-of-trp-channels-in-the-metastatic-cascade
#2
REVIEW
Benedikt Fels, Etmar Bulk, Zoltán Pethő, Albrecht Schwab
A dysregulated cellular Ca2+ homeostasis is involved in multiple pathologies including cancer. Changes in Ca2+ signaling caused by altered fluxes through ion channels and transporters (the transportome) are involved in all steps of the metastatic cascade. Cancer cells thereby "re-program" and "misuse" the cellular transportome to regulate proliferation, apoptosis, metabolism, growth factor signaling, migration and invasion. Cancer cells use their transportome to cope with diverse environmental challenges during the metastatic cascade, like hypoxic, acidic and mechanical cues...
May 17, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29748137/the-hidden-potential-of-lysosomal-ion-channels-a-new-era-of-oncogenes
#3
REVIEW
Andra M Sterea, Shekoufeh Almasi, Yassine El Hiani
Lysosomes serve as the control centre for cellular clearance. These membrane-bound organelles receive biomolecules destined for degradation from intracellular and extracellular pathways; thus, facilitating the production of energy and shaping the fate of the cell. At the base of their functionality are the lysosomal ion channels which mediate the function of the lysosome through the modulation of ion influx and efflux. Ion channels form pores in the membrane of lysosomes and allow the passage of ions, a seemingly simple task which harbours the potential of overthrowing the cell's stability...
March 10, 2018: Cell Calcium
https://www.readbyqxmd.com/read/29746898/two-pore-channels-and-disease
#4
REVIEW
Sandip Patel, Bethan S Kilpatrick
Two-pore channels (TPCs) are Ca2+ -permeable endo-lysosomal ion channels subject to multi-modal regulation. They mediate their physiological effects through releasing Ca2+ from acidic organelles in response to cues such as the second messenger, NAADP. Here, we review emerging evidence linking TPCs to disease. We discuss how perturbing both local and global Ca2+ changes mediated by TPCs through chemical and/or molecular manipulations can induce or reverse disease phenotypes. We cover evidence from models of Parkinson's disease, non-alcoholic fatty liver disease, Ebola infection, cancer, cardiac dysfunction and diabetes...
May 7, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29734668/emerging-roles-of-g-protein-coupled-receptors-in-hepatocellular-carcinoma
#5
REVIEW
Wen-Ting Peng, Wu-Yi Sun, Xin-Ran Li, Jia-Chang Sun, Jia-Jia Du, Wei Wei
Among a great variety of cell surface receptors, the largest superfamily is G protein-coupled receptors (GPCRs), also known as seven-transmembrane domain receptors. GPCRs can modulate diverse signal-transduction pathways through G protein-dependent or independent pathways which involve β-arrestins, G protein receptor kinases (GRKs), ion channels, or Src kinases under physiological and pathological conditions. Recent studies have revealed the crucial role of GPCRs in the tumorigenesis and the development of cancer metastasis...
May 4, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29725443/calcium-activated-potassium-channels-as-potential-early-markers-of-human-cervical-cancer
#6
Ana Ramírez, Eunice Vera, Armando Gamboa-Domínguez, Paul Lambert, Patricio Gariglio, Javier Camacho
Cervical cancer is a major cause of cancer-associated mortality in women in developing countries. Thus, novel early markers are required. Ion channels have gained great interest as tumor markers, including cervical cancer. The calcium-activated potassium channel KCNMA1 (subunit α-1 from subfamily M) has been associated with different malignancies, including tumors such as breast and ovarian cancer that are influenced by hormones. The KCNMA1 channel blocker iberiotoxin decreases the proliferation of HeLa cervical cancer cells...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29723550/scorpion-toxins-to-unravel-the-conundrum-of-ion-channel-structure-and-functioning
#7
Ernesto Ortiz, Lourival D Possani
The consequences of scorpion stings on the affected victims, including humans, have been known since ancient times. The effects of the venom, first on neurotransmission and thereafter on many physiological processes at the organism, tissue, cellular or molecular levels, have been the subject of intense research. It is, therefore, not surprising that a large number of toxins acting on a variety of ion channels have been isolated and described to date. Many of these toxins show high specificities and affinities towards their natural targets...
April 30, 2018: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29719628/novel-water-soluble-lignin-derivative-bp-cx-1-identification-of-components-and-screening-of-potential-targets-in-silico-and-in-vitro
#8
Elena I Fedoros, Alexey A Orlov, Alexander Zherebker, Ekaterina A Gubareva, Mikhail A Maydin, Andrey I Konstantinov, Konstantin A Krasnov, Ruben N Karapetian, Ekaterina I Izotova, Sergey E Pigarev, Andrey V Panchenko, Margarita L Tyndyk, Dmitry I Osolodkin, Evgeny N Nikolaev, Irina V Perminova, Vladimir N Anisimov
Identification of molecular targets and mechanism of action is always a challenge, in particular - for natural compounds due to inherent chemical complexity. BP-Cx-1 is a water-soluble modification of hydrolyzed lignin used as the platform for a portfolio of innovative pharmacological products aimed for therapy and supportive care of oncological patients. The present study describes a new approach, which combines in vitro screening of potential molecular targets for BP-Cx-1 using Diversity Profile - P9 panel by Eurofins Cerep (France) with a search of possible active components in silico in ChEMBL - manually curated chemical database of bioactive molecules with drug-like properties...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29717981/electron-cryo-microscopy-structure-of-the-canonical-trpc4-ion-channel
#9
Deivanayagabarathy Vinayagam, Thomas Mager, Amir Apelbaum, Arne Bothe, Felipe Merino, Oliver Hofnagel, Christos Gatsogiannis, Stefan Raunser
Canonical transient receptor channels (TRPC) are non-selective cation channels. They are involved in receptor-operated Ca2+ signaling and have been proposed to act as store-operated channels (SOC). Their malfunction is related to cardiomyopathies and their modulation by small molecules has been shown to be effective against renal cancer cells. The molecular mechanism underlying the complex activation and regulation is poorly understood. Here, we report the electron cryo-microscopy structure of zebrafish TRPC4 in its unliganded (apo), closed state at an overall resolution of 3...
May 2, 2018: ELife
https://www.readbyqxmd.com/read/29717355/the-function-of-trp-channels-in-neutrophil-granulocytes
#10
REVIEW
Karolina Najder, Boris Musset, Otto Lindemann, Etmar Bulk, Albrecht Schwab, Benedikt Fels
Neutrophil granulocytes are exposed to widely varying microenvironmental conditions when pursuing their physiological or pathophysiological functions such as fighting invading bacteria or infiltrating cancer tissue. Examples for harsh environmental challenges include among others mechanical shear stress during the recruitment from the vasculature or the hypoxic and acidotic conditions within the tumor microenvironment. Chemokine gradients, reactive oxygen species, pressure, matrix elasticity, and temperature can be added to the list of potential challenges...
May 1, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29682501/vdac1-as-pharmacological-target-in-cancer-and-neurodegeneration-focus-on-its-role-in-apoptosis
#11
REVIEW
Andrea Magrì, Simona Reina, Vito De Pinto
Cancer and neurodegeneration are different classes of diseases that share the involvement of mitochondria in their pathogenesis. Whereas the high glycolytic rate (the so-called Warburg metabolism) and the suppression of apoptosis are key elements for the establishment and maintenance of cancer cells, mitochondrial dysfunction and increased cell death mark neurodegeneration. As a main actor in the regulation of cell metabolism and apoptosis, VDAC may represent the common point between these two broad families of pathologies...
2018: Frontiers in Chemistry
https://www.readbyqxmd.com/read/29644475/electrophysiologic-toxicity-of-chemoradiation
#12
REVIEW
Merna A Armanious, Shreya Mishra, Michael G Fradley
PURPOSE OF REVIEW: There is growing awareness of the link between oncology treatments and cardiovascular (CV) complications. This has led to the development of cardio-oncology, a specialty aimed at managing CV risk and disease in cancer patients and survivors. Cardiac arrhythmias are potential adverse CV complications of cancer treatments; however, these cardiotoxicities are often underappreciated due to the uncertain arrhythmogenic mechanisms of various chemotherapeutic agents. RECENT FINDINGS: Chemotherapeutic agents can induce arrhythmias via direct electrophysiological effects on ion channels or intracellular signaling pathways, or indirectly from cardiac tissue damage...
April 11, 2018: Current Oncology Reports
https://www.readbyqxmd.com/read/29643996/selective-lysis-of-breast-carcinomas-by-simultaneous-stimulation-of-sodium-channels-and-blockade-of-sodium-pumps
#13
Harry J Gould, Jack Norleans, T David Ward, Chasiti Reid, Dennis Paul
Sodium influx through voltage-gated sodium channels (VGSCs) coupled with balanced removal of sodium ions via Na+ , K+ -ATPase is a major determinant of cellular homeostasis and intracellular ionic concentration. Interestingly, many metastatic carcinomas express high levels of these channels. We hypothesized that if excess VGSCs are activated and Na+ , K+ -ATPase is simultaneously blocked, the intracellular Na+ concentration should increase, resulting in water movement into the cell, causing swelling and lytic cell death...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29609141/exploring-the-novel-heterocyclic-derivatives-as-lead-molecules-for-design-and-development-of-potent-anticancer-agents
#14
Iqbal Azad, Malik Nasibullah, Tahmeena Khan, Firoj Hassan, Yusuf Akhter
This paper deals with in silico evaluation of newly proposed heterocyclic derivatives in search of potential anticancer activity. Best possible drug candidates have been proposed using a rational approach employing a pipeline of computational techniques namely MetaPrint2D prediction, molinspiration, cheminformatics, Osiris Data warrior, AutoDock and iGEMDOCK. Lazar toxicity prediction, AdmetSAR predictions, and targeted docking studies were also performed. 27 heterocyclic derivatives were selected for bioactivity prediction and drug likeness score on the basis of Lipinski's rule, Viber rule, Ghose filter, leadlikeness and Pan Assay Interference Compounds (PAINS) rule...
March 9, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29603454/an-ultrastable-ionic-chemiresistor-skin-with-an-intrinsically-stretchable-polymer-electrolyte
#15
Ming Liang Jin, Sangsik Park, Jong-Seon Kim, Sung Hyun Kwon, Shuye Zhang, Min Seok Yoo, Sungwoo Jang, Hyeong-Jun Koh, Soo-Yeon Cho, So Young Kim, Chi Won Ahn, Kilwon Cho, Seung Geol Lee, Do Hwan Kim, Hee-Tae Jung
Ultrastable sensing characteristics of the ionic chemiresistor skin (ICS) that is designed by using an intrinsically stretchable thermoplastic polyurethane electrolyte as a volatile organic compound (VOC) sensing channel are described. The hierarchically assembled polymer electrolyte film is observed to be very uniform, transparent, and intrinsically stretchable. Systematic experimental and theoretical studies also reveal that artificial ions are evenly distributed in polyurethane matrix without microscale phase separation, which is essential for implementing high reliability of the ICS devices...
March 30, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29601335/mechanosensitive-ion-channels-trpv4-and-p2x7-in-disseminating-cancer-cells
#16
Jacob M Hope, Joshua D Greenlee, Michael R King
Cancer metastasis is the second leading cause of death in the United States. Despite its morbidity, metastasis is an inefficient process that few cells can survive. However, cancer cells can overcome these metastatic barriers via cellular responses to microenvironmental cues, such as through mechanotransduction. This review focuses on the mechanosensitive ion channels TRPV4 and P2X7, and their roles in metastasis, as both channels have been shown to significantly affect tumor cell dissemination. Upon activation, these channels help form tumor neovasculature, promote transendothelial migration, and increase cell motility...
March 2018: Cancer Journal
https://www.readbyqxmd.com/read/29578501/capturing-the-interaction-kinetics-of-an-ion-channel-protein-with-small-molecules-by-the-bio-layer-interferometry-assay
#17
Bo Han, Man Zhang, Peng Sun, Shangwei Hou
The bio-layer interferometry (BLI) assay is a valuable tool for measuring protein-protein and protein-small molecule interactions. Here, we first describe the application of this novel label-free technique to study the interaction of human EAG1 (hEAG1) channel proteins with the small molecule PIP2. hEAG1 channel has been recognized as potential therapeutic target because of its aberrant overexpression in cancers and a few gain-of-function mutations involved in some types of neurological diseases. We purified hEAG1 channel proteins from a mammalian stable expression system and measured the interaction with PIP2 by BLI...
March 7, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29574724/extremely-thin-layer-plastification-for-focused-ion-beam-scanning-electron-microscopy-an-improved-method-to-study-cell-surfaces-and-organelles-of-cultured-cells
#18
E G VAN Donselaar, B Dorresteijn, D Popov-Čeleketić, W J VAN DE Wetering, T C Verrips, T Boekhout, C T W M Schneijdenberg, A T Xenaki, T P VAN DER Krift, W H Müller
Since the recent boost in the usage of electron microscopy in life-science research, there is a great need for new methods. Recently minimal resin embedding methods have been successfully introduced in the sample preparation for focused-ion beam scanning electron microscopy (FIB-SEM). In these methods several possibilities are given to remove as much resin as possible from the surface of cultured cells or multicellular organisms. Here we introduce an alternative way in the minimal resin embedding method to remove excess of resin from two widely different cell types by the use of Mascotte filter paper...
March 25, 2018: Journal of Microscopy
https://www.readbyqxmd.com/read/29549164/kir2-1-interaction-with-stk38-promotes-invasion-and-metastasis-of-human-gastric-cancer-by-enhancing-mekk2-mek1-2-erk1-2-signaling
#19
Cheng-Dong Ji, Yan-Xia Wang, Dong-Fang Xiang, Qiang Liu, Zhi-Hua Zhou, Feng Qian, Lang Yang, Yong Ren, Wei Cui, Sen-Lin Xu, Xi-Long Zhao, Xia Zhang, Yan Wang, Peng Zhang, Ji-Ming Wang, You-Hong Cui, Xiu-Wu Bian
Potassium ion channels are emerging as pro-malignant factors involved in cancer progression. In this study, we found that invading human gastric cancer (GC) cells express high level of inwardly rectifying potassium channel 2.1 (Kir2.1). Silencing Kir2.1 markedly reduced the invasive and metastatic capabilities as well as the epithelial-mesenchymal transition (EMT) of GC cells. The pro-malignant nature of Kir2.1 in GC cells was independent of potassium permeation but relied on its interaction with serine/threonine-protein kinase 38 (Stk38) to inhibit ubiquitination and degradation of mitogen-activated protein kinase kinase kinase 2 (MEKK2)...
March 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29536164/alternative-splicing-isoforms-in-health-and-disease
#20
REVIEW
Hyoung Kyu Kim, Michael Huy Cuong Pham, Kyung Soo Ko, Byoung Doo Rhee, Jin Han
Alternative splicing (AS) of protein-coding messenger RNAs is an essential regulatory mechanism in eukaryotic gene expression that controls the proper function of proteins. It is also implicated in the physiological regulation of mitochondria and various ion channels. Considering that mis-splicing can result in various human diseases by modifying or abrogating important physiological protein functions, a fine-tuned balance of AS is essential for human health. Accumulated data highlight the importance of alternatively spliced isoforms in various diseases, including neurodegenerative disorders, cancer, immune and infectious diseases, cardiovascular diseases, and metabolic conditions...
March 13, 2018: Pflügers Archiv: European Journal of Physiology
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