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https://www.readbyqxmd.com/read/28039451/high-throughput-proteome-analysis-reveals-targeted-trpm8-degradation-in-prostate-cancer
#1
Swapna Asuthkar, Lusine Demirkhanyan, Samuel Robert Mueting, Alejandro Cohen, Eleonora Zakharian
The Ca2+-permeable ion channel TRPM8 is a hallmark of the prostate epithelium. We recently discovered that TRPM8 is an ionotropic testosterone receptor. This finding suggested that testosterone-induced TRPM8 activity regulates Ca2+ homeostasis in the prostate epithelium. Since androgens are significantly implicated in prostate cancer development, the role of the novel testosterone receptor TRPM8 in cancer was assessed in our study. Although TRPM8 mRNA levels increase at the early prostate cancer stages, we found that it is not proportionally translated into TRPM8 protein levels...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28034363/the-screening-of-novel-inhibitors-against-leishmania-donovani-calcium-ion-channel-to-fight-leishmaniasis
#2
Mohammad Kashif, Partha Pratim Manna, Yusuf Akhter, Mohammed Alaidarous, Abdur Rub
Leishmania is an intracellular protozoan parasite which causes Leishmaniasis, a global health problem affecting millions of people throughout 89 different countries in the world. The current treatment which includes use of amphotericin B, antimonials, and others has major drawbacks due to toxicity, resistance, and extraordinary high cost. So there is an urgent need of development of new drug targets to fight against leishmaniasis. In this regard we have selected Leishmania donovani Ca2+ ion channel (Ld-CC) as potential drug target...
December 30, 2016: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/28009816/the-new-role-for-an-old-kinase-protein-kinase-ck2-regulates-metal-ion-transport
#3
REVIEW
Adam J Johnson, Ming J Wu
The pleiotropic serine/threonine protein kinase CK2 was the first kinase discovered. It is renowned for its role in cell proliferation and anti-apoptosis. The complexity of this kinase is well reflected by the findings of past decades in terms of its heterotetrameric structure, subcellular location, constitutive activity and the extensive catalogue of substrates. With the advent of non-biased high-throughput functional genomics such as genome-wide deletion mutant screening, novel aspects of CK2 functionality have been revealed...
December 21, 2016: Pharmaceuticals
https://www.readbyqxmd.com/read/28001342/triggering-mechanisms-and-inflammatory-effects-of-combustion-exhaust-particles-with-implication-for-carcinogenesis
#4
J Øvrevik, M Refsnes, M Låg, B Brinchmann, P E Schwarze, J A Holme
A number of biological responses may contribute to the carcinogenic effects of combustion-derived particulate matter (CPM). Here, we focus on mechanisms that trigger CPM-induced pro-inflammatory responses. Inflammation has both genotoxic as well as non-genotoxic implications and is considered to play a central role in development of various health outcomes associated with CPM exposure, including cancer. Chronic, low-grade inflammation may cause DNA damage through a persistent increased level of reactive oxygen species (ROS) produced and released by activated immune cells...
December 21, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27999995/lipid-glycosylation-a-primer-for-histochemists-and-cell-biologists
#5
REVIEW
Jürgen Kopitz
Glycolipids are glycoconjugates that are predominantly found on the extracellular surface of cells ranging from bacteria to men. In bacteria and plants, glycoglycerolipids represent the main glycolipid species. Ceramides as carrier for glycans, termed glycosphingolipids (GSLs), are characteristic for vertebrates and insects. The glycan part is involved in a variety of biological activities including cell adhesion and initiation of signaling. Most of these functions rest on two basic principles: (1) GSLs spontaneously contribute to organize lipid rafts in biological membranes, thereby forming functional complexes ('glycosynapses') with receptor proteins and ion channels and (2) their glycans are bound by receptors like galectins (protein-glycan recognition) or cognate glycans (glycan-glycan recognition)...
December 20, 2016: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/27986285/methods-for-monitoring-ca-2-and-ion-channels-in-the-lysosome
#6
REVIEW
Xi Zoë Zhong, Yiming Yang, Xue Sun, Xian-Ping Dong
Lysosomes and lysosome-related organelles are emerging as intracellular Ca(2+) stores and play important roles in a variety of membrane trafficking processes, including endocytosis, exocytosis, phagocytosis and autophagy. Impairment of lysosomal Ca(2+) homeostasis and membrane trafficking has been implicated in many human diseases such as lysosomal storage diseases (LSDs), neurodegeneration, myopathy and cancer. Lysosomal membrane proteins, in particular ion channels, are crucial for lysosomal Ca(2+) signaling...
December 9, 2016: Cell Calcium
https://www.readbyqxmd.com/read/27980223/extracellular-atp-induces-apoptosis-through-p2x7r-activation-in-acute-myeloid-leukemia-cells-but-not-in-normal-hematopoietic-stem-cells
#7
Valentina Salvestrini, Stefania Orecchioni, Giovanna Talarico, Francesca Reggiani, Cristina Mazzetti, Francesco Bertolini, Elisa Orioli, Elena Adinolfi, Francesco Di Virgilio, Annalisa Pezzi, Michele Cavo, Roberto M Lemoli, Antonio Curti
Recent studies have shown that high ATP levels exhibit direct cytotoxic effects on several cancer cells types. Among the receptors engaged by ATP, P2X7R is the most consistently expressed by tumors. P2X7R is an ATP-gated ion channel that could drive the opening of a non-selective pore, triggering cell-death signal. We previously demonstrated that acute myeloid leukemia (AML) cells express high level of P2X7R. Here, we show that P2X7R activation with high dose ATP induces AML blast cells apoptosis. Moreover, P2X7R is also expressed on leukemic stem/progenitor cells (LSCs) which are sensitive to ATP-mediated cytotoxicity...
December 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27980039/intracellular-calcium-mobilization-in-response-to-ion-channel-regulators-via-a-calcium-induced-calcium-release-mechanism
#8
Terry Petrou, Hervor L Olsen, Christopher Thrasivoulou, John R Masters, Jonathan F Ashmore, Aamir Ahmed
Free intracellular calcium ([Ca2+]i), in addition to being an important second messenger, is a key regulator of many cellular processes including cell membrane potential, proliferation and apoptosis. In many cases, the mobilization of [Ca2+]i is controlled by intracellular store activation and calcium influx. We have investigated the effect of several ion channel modulators, which have been used to treat a range of human diseases, on [Ca2+]i release, by ratiometric calcium imaging. We show that six such modulators (Amiodarone (Ami), Dofetilide (Dof), Furosemide (Fur), Minoxidil (Min), Loxapine (Lox), and Nicorandil (Nic)) initiate release of [Ca2+]i in prostate and breast cancer cell lines, PC3 and MCF7, respectively...
December 15, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27976908/weak-selectivity-predicted-for-modeled-bundles-of-viral-channel-forming-protein-e5-of-human-papillomavirus-16
#9
Dhani Ram Mahato, Wolfgang B Fischer
Protein E5 is a polytopic 83 amino acid membrane protein with three transmembrane domains (TMDs), encoded by high-risk human papillomavirus-16 (HPV-16). HPV-16 is found to be the causative agent for cervical cancer. Protein E5, among other proteins (e.g., E6, E7), is expressed at an "early" (E) stage when the cell turns malignant. It has been experimentally found that E5 forms hexameric assemblies, which show the characteristics of the class of so-called channel-forming proteins by rendering lipid membranes permeable to ions and small molecules...
December 29, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27956641/on-the-role-of-water-density-fluctuations-in-the-inhibition-of-a-proton-channel
#10
Eleonora Gianti, Lucie Delemotte, Michael L Klein, Vincenzo Carnevale
Hv1 is a transmembrane four-helix bundle that transports protons in a voltage-controlled manner. Its crucial role in many pathological conditions, including cancer and ischemic brain damage, makes Hv1 a promising drug target. Starting from the recently solved crystal structure of Hv1, we used structural modeling and molecular dynamics simulations to characterize the channel's most relevant conformations along the activation cycle. We then performed computational docking of known Hv1 inhibitors, 2-guanidinobenzimidazole (2GBI) and analogs...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27941930/erk-mediated-nf-%C3%AE%C2%BAb-activation-through-asic1-in-response-to-acidosis
#11
B Chen, J Liu, T-T Ho, X Ding, Y-Y Mo
Acidic microenvironment is a common feature of solid tumors. We have previously shown that neuron specific acid-sensing ion channel 1 (ASIC1) is expressed in breast cancer, and it is responsible for acidosis-induced cellular signaling through AKT, leading to nuclear factor-κB (NF-κB) activation, and cell invasion and metastasis. However, AKT is frequently activated in cancer. Thus, a key question is whether ASIC1-mediated cell signaling still takes place in the cancer cells carrying constitutively active AKT...
December 12, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27931022/hydrogen-sulfide-and-t-type-ca2-channels-in-pain-processing-neuronal-differentiation-and-neuroendocrine-secretion
#12
Kazuki Fukami, Fumiko Sekiguchi, Atsufumi Kawabata
BACKGROUND: Hydrogen sulfide (H2S), a gasotransmitter, is generated from L-cysteine by mainly 3 enzymes, cystathionine-γ-lyase (CSE), cystathionine-β-synthase, and 3-mercaptopyruvate sulfurtransferase in cooperation with cysteine aminotransferase. The H2S-forming enzymes, particularly CSE, are overexpressed under the pathological conditions such as inflammation, neuronal or neuroendocrine differentiation and cancer development. Given that Cav3.2 T-type Ca2+ channels mediate some of the biological activity of H2S, we focus on the role of the H2S/Cav3...
December 9, 2016: Pharmacology
https://www.readbyqxmd.com/read/27918554/asic1a-mediates-the-drug-resistance-of-human-hepatocellular-carcinoma-via-the-ca-2-pi3-kinase-akt-signaling-pathway
#13
Yihao Zhang, Ting Zhang, Chao Wu, Quan Xia, Dujuan Xu
Chemotherapy is the main treatment method of patients with advanced liver cancer. However, drug resistance is a serious problem in the treatment of hepatocellular carcinoma (HCC). Acid sensing ion channel 1a (ASIC1a) is a H(+)-gated cation channel; it mediates tumor cell migration and invasion, which suggests that it is involved in the development of malignant tumors. Therefore, we studied the relationship between ASIC1a and drug resistance in human hepatocellular carcinoma. In our study, we found that ASIC1a is highly expressed in human HCC tissue, and that its levels were significantly increased in resistant HCC cells Bel7402/FU and HepG2/ADM...
December 5, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27903970/ion-channels-in-control-of-pancreatic-stellate-cell-migration
#14
Hannah Storck, Benedikt Hild, Sandra Schimmelpfennig, Sarah Sargin, Nikolaj Nielsen, Angela Zaccagnino, Thomas Budde, Ivana Novak, Holger Kalthoff, Albrecht Schwab
Pancreatic stellate cells (PSCs) play a critical role in the progression of pancreatic ductal adenocarcinoma (PDAC). Once activated, PSCs support proliferation and metastasis of carcinoma cells. PSCs even co-metastasise with carcinoma cells. This requires the ability of PSCs to migrate. In recent years, it has been established that almost all "hallmarks of cancer" such as proliferation or migration/invasion also rely on the expression and function of ion channels. So far, there is only very limited information about the function of ion channels in PSCs...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27896999/identify-cancer-driver-genes-through-shared-mendelian-disease-pathogenic-variants-and-cancer-somatic-mutations
#15
Meng Ma, Changchang Wang, Benjamin S Glicksberg, Eric E Schadt, Shuyu D Li, Rong Chen
Genomic sequencing studies in the past several years have yielded a large number of cancer somatic mutations. There remains a major challenge in delineating a small fraction of somatic mutations that are oncogenic drivers from a background of predominantly passenger mutations. Although computational tools have been developed to predict the functional impact of mutations, their utility is limited. In this study, we applied an alternative approach to identify potentially novel cancer drivers as those somatic mutations that overlap with known pathogenic mutations in Mendelian diseases...
2016: Pacific Symposium on Biocomputing
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/27875305/-englerin-a-evoked-cytotoxicity-is-mediated-by-na-influx-and-counteracted-by-na-k-atpase
#17
Melanie J Ludlow, Hannah J Gaunt, Hussein N Rubaiy, Katie E Musialowski, Nicola M Blythe, Naveen S Vasudev, Katsuhiko Muraki, David J Beech
(-)-Englerin A ((-)-EA) has a rapid and potent cytotoxic effect on several types of cancer cell that is mediated by plasma membrane ion channels containing Transient Receptor Potential Canonical 4 protein (TRPC4). Since these channels are Ca2+ permeable it was initially thought that the cytotoxicity arose as a consequence of Ca2+ overload. Here we show that this is not the case and that the effect of (-)-EA is mediated by a heteromer of TRPC4 and TRPC1 proteins. Both TRPC4 and TRPC1 were required for (-)-EA cytotoxicity, however, although TRPC4 was necessary for the (-)-EA-evoked Ca2+-elevation, TRPC1 was not...
November 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27856238/evaluation-of-known-and-novel-inhibitors-of-orai1-mediated-store-operated-ca-2-entry-in-mda-mb-231-breast-cancer-cells-using-a-fluorescence-imaging-plate-reader-assay
#18
Iman Azimi, Jack U Flanagan, Ralph J Stevenson, Marco Inserra, Irina Vetter, Gregory R Monteith, William A Denny
The Orai1 Ca(2+) permeable ion channel is an important component of store operated Ca(2+) entry (SOCE) in cells. It's over-expression in basal molecular subtype breast cancers has been linked with poor prognosis, making it a potential target for drug development. We pharmacologically characterised a number of reported inhibitors of SOCE in MDA-MB-231 breast cancer cells using a convenient Fluorescence Imaging Plate Reader (FLIPR) assay, and show that the rank order of their potencies in this assay is the same as those reported in a wide range of published assays...
January 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27845746/an-overview-of-sub-cellular-mechanisms-involved-in-the-action-of-ttfields
#19
REVIEW
Jack A Tuszynski, Cornelia Wenger, Douglas E Friesen, Jordane Preto
Long-standing research on electric and electromagnetic field interactions with biological cells and their subcellular structures has mainly focused on the low- and high-frequency regimes. Biological effects at intermediate frequencies between 100 and 300 kHz have been recently discovered and applied to cancer cells as a therapeutic modality called Tumor Treating Fields (TTFields). TTFields are clinically applied to disrupt cell division, primarily for the treatment of glioblastoma multiforme (GBM). In this review, we provide an assessment of possible physical interactions between 100 kHz range alternating electric fields and biological cells in general and their nano-scale subcellular structures in particular...
November 12, 2016: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/27835900/kcnj3-is-a-new-independent-prognostic-marker-for-estrogen-receptor-positive-breast-cancer-patients
#20
Sarah Kammerer, Armin Sokolowski, Hubert Hackl, Dieter Platzer, Stephan Wenzel Jahn, Amin El-Heliebi, Daniela Schwarzenbacher, Verena Stiegelbauer, Martin Pichler, Simin Rezania, Heidelinde Fiegl, Florentia Peintinger, Peter Regitnig, Gerald Hoefler, Wolfgang Schreibmayer, Thomas Bauernhofer
Numerous studies showed abnormal expression of ion channels in different cancer types. Amongst these, the potassium channel gene KCNJ3 (encoding for GIRK1 proteins) has been reported to be upregulated in tumors of patients with breast cancer and to correlate with positive lymph node status. We aimed to study KCNJ3 levels in different breast cancer subtypes using gene expression data from the TCGA, to validate our findings using RNA in situ hybridization in a validation cohort (GEO ID GSE17705), and to study the prognostic value of KCNJ3using survival analysis...
November 8, 2016: Oncotarget
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