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Ion metabolism cancer

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https://www.readbyqxmd.com/read/29028058/protein-protein-interaction-networks-as-a-new-perspective-to-evaluate-distinct-functional-roles-of-voltage-dependent-anion-channel-isoforms
#1
REVIEW
Marianna Caterino, Margherita Ruoppolo, Annalisa Mandola, Michele Costanzo, Stefania Orrù, Esther Imperlini
Voltage-dependent anion channels (VDACs) are a family of three mitochondrial porins and the most abundant integral membrane proteins of the mitochondrial outer membrane (MOM). VDACs are known to be involved in metabolite/ion transport across the MOM and in many cellular processes ranging from mitochondria-mediated apoptosis to the control of energy metabolism, by interacting with cytosolic, mitochondrial and cytoskeletal proteins and other membrane channels. Despite redundancy and compensatory mechanisms among VDAC isoforms, they display not only different channel properties and protein expression levels, but also distinct protein partners...
October 13, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28986220/two-mutations-in-mitochondrial-atp6-gene-of-atp-synthase-related-to-human-cancer-affect-ros-calcium-homeostasis-and-mitochondrial-permeability-transition-in-yeast
#2
Katarzyna Niedzwiecka, Renata Tisi, Sara Penna, Malgorzata Lichocka, Danuta Plochocka, Roza Kucharczyk
The relevance of mitochondrial DNA (mtDNA) mutations in cancer process is still unknown. Since the mutagenesis of mitochondrial genome in mammals is not possible yet, we have exploited budding yeast S. cerevisiae as a model to study the effects of tumor-associated mutations in the mitochondrial MTATP6 gene, encoding subunit 6 of ATP synthase, on the energy metabolism. We previously reported that four mutations in this gene have a limited impact on the production of cellular energy. Here we show that two mutations, Atp6-P163S and Atp6-K90E (human MTATP6-P136S and MTATP6-K64E, found in prostate and thyroid cancer samples, respectively), increase sensitivity of yeast cells both to compounds inducing oxidative stress and to high concentrations of calcium ions in the medium, when Om45p, the component of porin complex in outer mitochondrial membrane (OM), was fused to GFP...
October 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28983581/bioinformatics-analysis-of-fibroblasts-exposed-to-tgf%C3%A2-%C3%AE-at-the-early-proliferation-phase-of-wound-repair
#3
Bobin Mi, Guohui Liu, Wu Zhou, Huijuan Lv, Kun Zha, Yi Liu, Qipeng Wu, Jing Liu
The aim of the current study was to identify gene signatures during the early proliferation stage of wound repair and the effect of TGF‑β on fibroblasts and reveal their potential mechanisms. The gene expression profiles of GSE79621 and GSE27165 were obtained from GEO database. Differentially expressed genes (DEGs) were identified using Morpheus and co‑expressed DEGs were selected using Venn Diagram. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool...
September 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28977850/integrated-transcriptomic-analysis-of-distance-related-field-cancerization-in-rectal-cancer-patients
#4
Honglin Guo, Weigen Zeng, Lin Feng, Xuexin Yu, Ping Li, Kaitai Zhang, Zhixiang Zhou, Shujun Cheng
Field cancerization (FC) occurs in various epithelial carcinomas, including colorectal cancer, which indicates that the molecular events in carcinogenesis might occur in normal tissues extending from tumors. However, the transcriptomic characteristics of FC in colorectal cancer (CRC) remain largely unexplored. To investigate the changes in gene expression associated with proximity to the tumor, we analyzed the global gene expression profiles of cancer tissues and histologically normal tissues taken at various distances from the tumor (1 cm, 5 cm and the proximal end of the resected sample) from 32 rectal cancer patients...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28944060/one-ion-to-rule-them-all-combined-antibacterial-osteoinductive-and-anticancer-properties-of-selenite-incorporated-hydroxyapatite
#5
Vuk Uskoković, Maheshwar Adiraj Iyer, Victoria M Wu
Although hydroxyapatite (HAp) has been doped with dozens of different ions, the quest for an ion imparting a combination of properties conducive to bone healing is still ongoing. Because of its protean potency and the similarity in size and shape to the phosphate tetrahedron, selenite ion presents a natural ionic substitute in HAp. The incorporation of selenite into synthetic HAp using two different methods - co-precipitation and ion-exchange sorption - was studied for its effect on crystal properties and on a triad of biological responses: antibacterial, anticancer and osteoinductive...
2017: Journal of Materials Chemistry. B, Materials for Biology and Medicine
https://www.readbyqxmd.com/read/28936716/induction-of-reactive-oxygen-species-an-emerging-approach-for-cancer-therapy
#6
REVIEW
Zhengzhi Zou, Haocai Chang, Haolong Li, Songmao Wang
Reactive oxygen species (ROS), a group of ions and molecules, include hydroxyl radicals (·OH), alkoxyl radicals, superoxide anion (O2·-), singlet oxygen ((1)O2) and hydrogen peroxide (H2O2). Hydroxyl radicals and alkoxyl radicals are extremely and highly reactive species respectively. Endogenous ROS are mainly formed in mitochondrial respiratory chain. Low levels of ROS play important roles in regulating biological functions in mammalian cells. However, excess production of ROS can induce cell death by oxidative damaging effects to intracellular biomacromolecules...
September 21, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28934848/profiling-of-serum-metabolites-using-maldi-tof-and-triple-tof-mass-spectrometry-to-develop-a-screen-for-ovarian-cancer
#7
Jun Hwa Lee, Yun Hwan Kim, Kyung-Hee Kim, Jae Youl Cho, Sang Myung Woo, Byong Chul Yoo, Seung Cheol Kim
Purpose: We sought to develop a matrix assisted laser desorption ionization-time of flight (MALDI-TOF)-based, ovarian cancer (OVC), low-mass-ion discriminant equation (LOME) and to evaluate a possible supportive role for triple-TOF mass analysis in identifying metabolic biomarkers. Materials and Methods: A total of 114 serum samples from patients with OVC and benign ovarian tumors were subjected to MALDI-TOF analysis and a total of 137 serum samples from healthy female individuals and patients with OVC, colorectal cancer, hepatobiliary cancer, and pancreatic cancer were subjected to triple-TOF analysis...
September 18, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28913175/regulation-of-endoplasmic-reticulum-mitochondria-ca-2-transfer-and-its-importance-for-anti-cancer-therapies
#8
REVIEW
Gaia Pedriali, Alessandro Rimessi, Luigi Sbano, Carlotta Giorgi, Mariusz R Wieckowski, Maurizio Previati, Paolo Pinton
Inter-organelle membrane contact sites are emerging as major sites for the regulation of intracellular Ca(2+) concentration and distribution. Here, extracellular stimuli operate on a wide array of channels, pumps, and ion exchangers to redistribute intracellular Ca(2+) among several compartments. The resulting highly defined spatial and temporal patterns of Ca(2+) movement can be used to elicit specific cellular responses, including cell proliferation, migration, or death. Plasma membrane (PM) also can directly contact mitochondria and endoplasmic reticulum (ER) through caveolae, small invaginations of the PM that ensure inter-organelle contacts, and can contribute to the regulation of numerous cellular functions through scaffolding proteins such as caveolins...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28912578/tumour-acidosis-from-the-passenger-to-the-driver-s-seat
#9
REVIEW
Cyril Corbet, Olivier Feron
The high metabolic demand of cancer cells leads to an accumulation of H(+) ions in the tumour microenvironment. The disorganized tumour vasculature prevents an efficient wash-out of H(+) ions released into the extracellular medium but also favours the development of tumour hypoxic regions associated with a shift towards glycolytic metabolism. Under hypoxia, the final balance of glycolysis, including breakdown of generated ATP, is the production of lactate and a stoichiometric amount of H(+) ions. Another major source of H(+) ions results from hydration of CO2 produced in the more oxidative tumour areas...
October 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28901272/disorders-of-mechanisms-of-calcium-metabolism-control-as-potential-risk-factors-of-prostate-cancer
#10
Dorota Skrajnowska, Barbara Bobrowska-Korczak, Andrzej Tokarz
Prostate cancer significantly affects the overall morbidity and mortality of malignant tumours in highly developed countries. Important risk factors include family predisposition and regional, racial and dietary determinants. The scientific literature contains a great deal of data on the role of calcium and dairy products in general in the process of neoplastic transformation of the prostate. This is most likely linked to the fact that changes in the concentration of calcium ions control such varied life processes as secretion of hormones and neurotransmitters, the level of cyclic nucleotides, and cell growth, division and differentiation...
September 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28894629/isolation-characterization-and-in-silico-docking-studies-of-synergistic-estrogen-receptor-a-anticancer-polyphenols-from-syzygium-alternifolium-wt-walp
#11
Pulicherla Yugandhar, Konidala Kranthi Kumar, Pabbaraju Neeraja, Nataru Savithramma
AIM: This study aims to isolate, characterize, and in silico evaluate of anticancer polyphenols from different parts of Syzygium alternifolium. MATERIALS AND METHODS: The polyphenols were isolated by standard protocol and characterized using Fourier-transform infrared (FT-IR), High performance liquid chromatography - Photodiode array detector coupled with Electrospray ionization - mass spectrometry (MS/MS). The compounds were elucidated based on retention time and molecular ions (m/z) either by [M+H](+)/[M-H](-) with the comparison of standard phenols as well as ReSpect software tool...
July 2017: Journal of Intercultural Ethnopharmacology
https://www.readbyqxmd.com/read/28883041/normoxic-cells-remotely-regulate-the-acid-base-balance-of-cells-at-the-hypoxic-core-of-connexin-coupled-tumor-growths
#12
Tobias H Dovmark, Alzbeta Hulikova, Steven A Niederer, Richard D Vaughan-Jones, Pawel Swietach
ATP fuels the removal of metabolic end-products, including H(+) ions that profoundly modulate biological activities. Energetic resources in hypoxic tumor regions are constrained by low-yielding glycolysis, and any means of reducing the cost of acid extrusion, without compromising pH homeostasis, would therefore be advantageous for cancer cells. Some cancers express connexin channels that allow solute exchange between cells, and we propose that, via this route, normoxic cells supply hypoxic neighbors with acid-neutralizing HCO3(-) ions...
September 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28815518/organelle-communication-at-membrane-contact-sites-mcs-from-curiosity-to-center-stage-in-cell-biology-and-biomedical-research
#13
Thomas Simmen, Mitsuo Tagaya
Cell biology has long recognized that organelles can communicate with each other. Initially, such communication was thought to occur primarily via vesicular trafficking between biochemically distinct organelles. However, studies starting in the 1970s on lipid metabolism have unearthed another way how organelles can communicate and have spawned the field of membrane contact sites (MCS). While, initially, MCS had been recognized as fluid entities that mediate lipid and ion transport in an ad hoc manner, more recently MCS have been found to depend on protein-protein interactions that control themselves a variety of MCS functions...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28743078/metabolite-identification-of-azd8055-in-sprague-dawley-rats-after-a-single-oral-administration-using-ultra-performance-liquid-chromatography-and-mass-spectrometry
#14
Md Mamunur Rashid, Hyun-A Oh, Hyunbeom Lee, Byung Hwa Jung
AZD8055 is an ATP-competitive specific dual mTOR inhibitor and exhibited potent antitumor activity on several types of solid tumors. However, the metabolism of AZD8055 in the body still remains unknown. In this study, metabolite identification of AZD8055 was performed using ultra high-performance liquid chromatography-ion trap mass spectrometry (UHPLC-IT-MS) through both in vitro and in vivo approaches using rat liver microsomes (RLMs) and rat plasma, urine and feces, respectively. A total of eight putative metabolites (five phase I and three phase II) were identified, and a tentative metabolic pathway was suggested for the first time...
October 25, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28730494/deconstructing-the-metabolic-networks-of-oncogenic-signaling-using-targeted-liquid-chromatography-tandem-mass-spectrometry-lc-ms-ms
#15
George Poulogiannis
Metabolic reprogramming is recognized as an emerging hallmark of oncogenic signaling and cancer development. Hence the need to identify novel quantitative analytical platforms for studying metabolism in vitro and in vivo has dramatically increased. Here, we describe the experimental workflow for a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach involving positive/negative ion switching to analyze >250 metabolites of central carbon metabolism, nucleotides, and amino acids.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28725634/ip3-receptor-mediated-calcium-signaling-and-its-role-in-autophagy-in-cancer
#16
REVIEW
Elzbieta Kania, Gemma Roest, Tim Vervliet, Jan B Parys, Geert Bultynck
Calcium ions (Ca(2+)) play a complex role in orchestrating diverse cellular processes, including cell death and survival. To trigger signaling cascades, intracellular Ca(2+) is shuffled between the cytoplasm and the major Ca(2+) stores, the endoplasmic reticulum (ER), the mitochondria, and the lysosomes. A key role in the control of Ca(2+) signals is attributed to the inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), the main Ca(2+)-release channels in the ER. IP3Rs can transfer Ca(2+) to the mitochondria, thereby not only stimulating core metabolic pathways but also increasing apoptosis sensitivity and inhibiting basal autophagy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28713289/mitochondrial-vdac1-a-key-gatekeeper-as-potential-therapeutic-target
#17
REVIEW
Amadou K S Camara, YiFan Zhou, Po-Chao Wen, Emad Tajkhorshid, Wai-Meng Kwok
Mitochondria are the key source of ATP that fuels cellular functions, and they are also central in cellular signaling, cell division and apoptosis. Dysfunction of mitochondria has been implicated in a wide range of diseases, including neurodegenerative and cardiac diseases, and various types of cancer. One of the key proteins that regulate mitochondrial function is the voltage-dependent anion channel 1 (VDAC1), the most abundant protein on the outer membrane of mitochondria. VDAC1 is the gatekeeper for the passages of metabolites, nucleotides, and ions; it plays a crucial role in regulating apoptosis due to its interaction with apoptotic and anti-apoptotic proteins, namely members of the Bcl-2 family of proteins and hexokinase...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28713156/discovery-of-a-novel-calcium-sensitive-fluorescent-probe-for-%C3%AE-ketoglutarate
#18
Lin-Lin Gan, Lin-Hai Chen, Fa-Jun Nan
α-Ketoglutarate (α-KG), a pivotal metabolite in energy metabolism, has been implicated in nonalcoholic fatty liver disease (NAFLD) and several cancers. It is recently proposed that plasma α-KG is a surrogate biomarker of NAFLD. Here, we report the development of a novel "turn-on" chemosensor for α-KG that contains a coumarin moiety as a fluorophore. Using benzothiazole-coumarin (BTC) as inspiration, we designed a probe for calcium ion recognition that possesses a unique fluorophore compared with previously reported probes for α-KG measurement...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28706220/opportunities-for-therapeutic-antibodies-directed-at-g-protein-coupled-receptors
#19
REVIEW
Catherine J Hutchings, Markus Koglin, William C Olson, Fiona H Marshall
G-protein-coupled receptors (GPCRs) are activated by a diverse range of ligands, from large proteins and proteases to small peptides, metabolites, neurotransmitters and ions. They are expressed on all cells in the body and have key roles in physiology and homeostasis. As such, GPCRs are one of the most important target classes for therapeutic drug discovery. The development of drugs targeting GPCRs has therapeutic value across a wide range of diseases, including cancer, immune and inflammatory disorders as well as neurological and metabolic diseases...
September 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28698214/papers-of-note-in-nature547-7661
#20
Annalisa M VanHook
This week's articles highlight progress in predicting T cell receptor specificity; an evolutionarily ancient form of antiviral defense; a mechanism of chemotherapy-induced cell death; metabolic rewiring in cancer cells; and structural insights into activation of a GPCR and of a mechanosensitive ion channel.
July 11, 2017: Science Signaling
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