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Oxygen mediated ion channels

Lei Bao, Shu-Jen Chen, Kathleen Conrad, Kerry Keefer, Thomas Abraham, John P Lee, JuFang Wang, Xue-Qian Zhang, Iwona Hirschler-Laszkiewicz, Hong-Gang Wang, Sinisa Dovat, Brian Gans, Muniswamy Madesh, Joseph Y Cheung, Barbara A Miller
Transient Receptor Potential Melastatin 2 (TRPM2) ion channel has an essential function in modulating cell survival following oxidant injury and is highly expressed in many cancers including neuroblastoma. Here, in xenografts generated from neuroblastoma cells in which TRPM2 was depleted with CRISPR/Cas9 technology and in in vitro experiments, tumor growth was significantly inhibited and doxorubicin sensitivity increased. The hypoxia-inducible transcription factor 1/2α (HIF-1/2α) signaling cascade including proteins involved in oxidant stress, glycolysis and mitochondrial function was suppressed by TRPM2 depletion...
September 30, 2016: Journal of Biological Chemistry
N M Mazure
The voltage-dependent anion channel (VDAC) is the main interface between the cytosol and mitochondria of cells. It plays a crucial role in both mitochondrial metabolism and cell death. The main basic function of this channel is to mediate and gate the flux of small ions, metabolites, and adenosine triphosphate. Changes in its structure, and thus conformation, are expected to affect its activity and modulate the ability of cancer cells to expand. In this review, we describe a novel mechanism by which mitochondria of cells in hypoxia, a low level of oxygen, protects from apoptosis...
2016: Frontiers in Oncology
Kangway V Chuang, Chen Xu, Sarah E Reisman
(+)-Ryanodine and (+)-ryanodol are complex diterpenoids that modulate intracellular calcium-ion release at ryanodine receptors, ion channels critical for skeletal and cardiac muscle excitation-contraction coupling and synaptic transmission. Chemical derivatization of these diterpenoids has demonstrated that certain peripheral structural modifications can alter binding affinity and selectivity among ryanodine receptor isoforms. Here, we report a short chemical synthesis of (+)-ryanodol that proceeds in only 15 steps from the commercially available terpene (S)-pulegone...
August 26, 2016: Science
Eskedar Ayele Angamo, Joerg Roesner, Agustin Liotta, Richard Kovacs, Uwe Heinemann
Astrocyte derived lactate supports pathologically enhanced neuronal metabolism but its role under physiological conditions is still a matter of debate. Here, we determined the contribution of astrocytic neuronal lactate shuttle to maintenance of ion homeostasis and energy metabolism. We tested for the effects of α-cyano-4-hydroxycinnamic acid (4-CIN), which could interfere with energy metabolism by blocking monocarboxylate-transporter 2 (MCT2) mediated neuronal lactate uptake, on evoked potentials, stimulus induced changes in K(+), Na(+), Ca(2+) and oxygen concentrations as well as on changes in flavin adenine dinucleotide (FAD) autofluorescence in the hippocampal area CA3...
August 24, 2016: Journal of Neurophysiology
Ilya Kovalenko, Andrea Glasauer, Laura Schöckel, Daniel R P Sauter, Alexander Ehrmann, Florian Sohler, Andrea Hägebarth, Ivana Novak, Sven Christian
Pancreatic ductal adenocarcinoma (PDAC) represents the most common form of pancreatic cancer with rising incidence in developing countries and overall 5-year survival rates of less than 5%. The most frequent mutations in PDAC are gain-of-function mutations in KRAS as well as loss-of-function mutations in p53. Both mutations have severe impacts on the metabolism of tumor cells. Many of these metabolic changes are mediated by transporters or channels that regulate the exchange of metabolites and ions between the intracellular compartment and the tumor microenvironment...
2016: PloS One
Hideo Kimura
Hydrogen sulfide (H2S) is a physiological mediator with various roles, including neuro-modulation, vascular tone regulation, and cytoprotection against ischemia-reperfusion injury, angiogenesis, and oxygen sensing. Hydrogen polysulfide (H2S n ), which possesses a higher number of sulfur atoms than H2S, recently emerged as a potential signaling molecule that regulates the activity of ion channels, a tumor suppressor, transcription factors, and protein kinases. Some of the previously reported effects of H2S are now attributed to the more potent H2S n ...
November 2016: Journal of Neural Transmission
S Beceiro, J N Radin, R Chatuvedi, M B Piazuelo, D J Horvarth, H Cortado, Y Gu, B Dixon, C Gu, I Lange, D-Lt Koomoa, K T Wilson, H M S Algood, S Partida-Sánchez
Calcium signaling in phagocytes is essential for cellular activation, migration, and the potential resolution of infection or inflammation. The generation of reactive oxygen species (ROS) via activation of NADPH (nicotinamide adenine dinucleotide phosphate)-oxidase activity in macrophages has been linked to altered intracellular calcium concentrations. Because of its role as an oxidative stress sensor in phagocytes, we investigated the function of the cation channel transient receptor potential melastatin 2 (TRPM2) in macrophages during oxidative stress responses induced by Helicobacter pylori infection...
July 20, 2016: Mucosal Immunology
Jessica L Ross, Luis F Queme, Elysia R Cohen, Kathryn J Green, Peilin Lu, Aaron T Shank, Suzie An, Renita C Hudgins, Michael P Jankowski
UNLABELLED: Musculoskeletal pain is a significantly common clinical complaint. Although it is known that muscles are quite sensitive to alterations in blood flow/oxygenation and a number of muscle pain disorders are based in problems of peripheral perfusion, the mechanisms by which ischemic-like conditions generate myalgia remain unclear. We found, using a multidisciplinary experimental approach, that ischemia and reperfusion injury (I/R) in male Swiss Webster mice altered ongoing and evoked pain-related behaviors in addition to activity levels through enhanced muscle interleukin-1 beta (IL1β)/IL1 receptor signaling to group III/IV muscle afferents...
June 29, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Plamena R Angelova, Andrey Y Abramov
The major energy generator in the cell - mitochondria produce reactive oxygen species as a by-product of a number of enzymatic reactions and the production of ATP. Emerging evidence suggests that mitochondrial ROS regulate diverse physiological parameters and that dysregulated ROS signalling may contribute to a development of processes which lead to human diseases. ROS produced in mitochondrial enzymes are triggers of monoamine-induced calcium signal in astrocytes, playing important role in physiological and pathophysiological response to dopamine...
June 10, 2016: Free Radical Biology & Medicine
Lei Pei, Glenn Solis, Mien T X Nguyen, Nikhil Kamat, Lynn Magenheimer, Min Zhuo, Jiahua Li, Joshua Curry, Alicia A McDonough, Timothy A Fields, William J Welch, Alan S L Yu
Efficient oxygen utilization in the kidney may be supported by paracellular epithelial transport, a form of passive diffusion that is driven by preexisting transepithelial electrochemical gradients. Claudins are tight-junction transmembrane proteins that act as paracellular ion channels in epithelial cells. In the proximal tubule (PT) of the kidney, claudin-2 mediates paracellular sodium reabsorption. Here, we used murine models to investigate the role of claudin-2 in maintaining energy efficiency in the kidney...
July 1, 2016: Journal of Clinical Investigation
Hieu T H Nguyen, Kenji Umemura, Tomonori Kawano
Indole-3-acetic acid (IAA) is the major natural auxin involved in the regulation of a variety of growth and developmental processes such as division, elongation, and polarity determination in growing plant cells. It has been shown that dividing and/or elongating plant cells accompanies the generation of reactive oxygen species (ROS) and a number of reports have suggested that hormonal actions can be mediated by ROS through ROS-mediated opening of ion channels. Here, we surveyed the link between the action of IAA, oxidative burst, and calcium channel activation in a transgenic cells of rice expressing aequorin in the cytosol...
August 2016: Bioscience, Biotechnology, and Biochemistry
Haim Shapiro, Pierre Singer, Amiram Ariel
Pain is a complex sensation that may be protective or cause undue suffering and loss of function, depending on the circumstances. Peripheral nociceptor neurons (PNs) innervate most tissues, and express ion channels, nocisensors, which depolarize the cell in response to intense stimuli and numerous substances. Inflamed tissues manifest inflammatory hyperalgesia in which the threshold for pain and the response to painful stimuli are decreased and increased, respectively. Constituents of the inflammatory milieu sensitize PNs, thereby contributing to hyperalgesia...
August 2016: Prostaglandins, Leukotrienes, and Essential Fatty Acids
Aditi Banerjee, Swagata Ghatak, Sujit Kumar Sikdar
Brain ischaemia is a highly debilitating condition where shortage of oxygen and glucose leads to profuse cell death. Lactate is a neuroprotective metabolite whose concentrations increase up to 15-30 mmol/L during ischaemia and TREK1 is a neuroprotective potassium channel which is upregulated during ischaemia. The aim of this study was to investigate the effect of l-lactate on TREK1 expression and to evaluate the role of l-lactate-TREK1 interaction in conferring neuroprotection in ischaemia-prone hippocampus...
July 2016: Journal of Neurochemistry
Yu V Karpets, Yu E Kolupaev, T O Yastreb
The effects of functional interplay of calcium ions, reactive oxygen species (ROS) and nitric oxide (NO) in the cells of wheat plantlets roots (Triticum aestivum L.) at the induction of their heat resistance by a short-term influence of hyperthermia (heating at the temperature of 42 degrees C during 1 minute) have been investigated. The transitional increase of NO and H2O2 content, invoked by heating, was suppressed by the treatment of plantlets with the antagonists of calcium EGTA (chelator of exocellular calcium), lanthanum chloride (blocker of calcium channels of various types) and neomycin (inhibitor of phosphatidylinositol-dependent phospholipase C)...
November 2015: Ukrainian Biochemical Journal
Tamjeed A Siddiqui, Starlee Lively, Lyanne C Schlichter
BACKGROUND: Microglia are the "professional" phagocytes of the CNS. Phagocytosis is crucial for normal CNS development and maintenance, but it can be either beneficial or detrimental after injury or disease. For instance, white matter damage releases myelin debris that must be cleared by microglia in order for re-myelination to occur. However, phagocytosis can also produce damaging reactive oxygen species (ROS). Furthermore, microglia can acquire pro-inflammatory (M1) or anti-inflammatory (M2) activation states that affect cell functions...
2016: Journal of Neuroinflammation
Jixiang Zhang, Xiaoli Wang, Vikash Vikash, Qing Ye, Dandan Wu, Yulan Liu, Weiguo Dong
It has long been recognized that an increase of reactive oxygen species (ROS) can modify the cell-signaling proteins and have functional consequences, which successively mediate pathological processes such as atherosclerosis, diabetes, unchecked growth, neurodegeneration, inflammation, and aging. While numerous articles have demonstrated the impacts of ROS on various signaling pathways and clarify the mechanism of action of cell-signaling proteins, their influence on the level of intracellular ROS, and their complex interactions among multiple ROS associated signaling pathways, the systemic summary is necessary...
2016: Oxidative Medicine and Cellular Longevity
Celio X C Santos, Sadaf Raza, Ajay M Shah
The specific effect of oxygen and reactive oxygen species (ROS) in mediating post-translational modification of protein targets has emerged as a key mechanism regulating signaling components, a process termed redox signaling. ROS act in the post-translational modification of multiple target proteins including receptors, kinases, phosphatases, ion channels and transcription factors. Both O2 and ROS are major source of electrons in redox reactions in aerobic organisms. Because the heart has the highest O2 consumption among body organs, it is not surprising that redox signaling is central to heart function and pathophysiology...
May 2016: International Journal of Biochemistry & Cell Biology
Ting Zhou, Ming-Shan Chien, Safa Kaleem, Hiroaki Matsunami
KEY POINTS: Carotid body (CB) glomus cells mediate acute oxygen sensing and the initiation of the hypoxic ventilatory response, yet the gene expression profile of these cells is not available. We demonstrate that the single cell RNA-Seq method is a powerful tool for identifying highly expressed genes in CB glomus cells. Our single cell RNA-Seq results characterized novel CB glomus cell genes, including members of the G protein-coupled receptor signalling pathway, ion channels and atypical mitochondrial electron transport chain subunits...
August 1, 2016: Journal of Physiology
Yan Huang, Fabiao Yu, Jianchao Wang, Lingxin Chen
H2S plays important physiological and pathological roles in the cardiovascular system and nervous system. However, recent evidence imply that hydrogen polysulfides (H2Sn) are the actual signaling molecules in cells. Although H2Sn have been demonstrated to be responsible for mediating tumor suppressors, ion channels, and transcription factors, more of their biological effects are still need to be elaborated. On one hand, H2Sn have been suggested to be generated from endogenous H2S upon reaction with reactive oxygen species (ROS)...
April 5, 2016: Analytical Chemistry
Nicole J Rijs, Patricio González-Navarrete, Maria Schlangen, Helmut Schwarz
Traveling wave ion mobility spectrometry (TWIMS) isomer separation was exploited to react the particularly well-defined ionic species [LCuO](+) (L = 1,10-phenanthroline) with the neutral fluoromethane substrates CH(4-n)Fn (n = 1-3) in the gas phase. Experimentally, the monofluoromethane substrate (n = 1) undergoes both hydrogen-atom transfer, forming the copper hydroxide complex [LCuOH](•+) and concomitantly a CH2F(•) radical, and oxygen-atom transfer, yielding the observable ionic product [LCu](+) plus the neutral oxidized substrate [C,H3,O,F]...
March 9, 2016: Journal of the American Chemical Society
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