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Cellular physiological approach for treatment of gastric cancer

World Journal of Gastroenterology 2014年第33期20卷 11560-11566页

作者： Atsushi Shiozaki Daisuke Ichikawa Eigo Otsuji Yoshinori Marunaka Division of Digestive Surgery Department of Surgery Kyoto Prefectural University of Medicine Kyoto 602-8566 Japan Departments of Molecular Cell Physiology and Bio-Ionomics Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto 602-8566 Japan Japan Institute for Food Education and Health St. Agnes’ University Kyoto 602-8013 Japan

Recent studies show that ion channels/transporters play important roles in fundamental cellular functions that would be involved in the cancer process. We review the evidence for their expression and functioning in human gastric cancer (GC), and evaluate the potential of cellular physiological approach in clinical management. Various types of ion channels, such as voltage-gated K+ channels, intracellular Cl- channels and transient receptor potential channels have been found to express in GC cells and tissues, and to control cell cycles. With regard to water channels, aquaporin 3 and 5 play an important role in the progression of GC. Regulators of intracellular pH, such as anion exchanger, sodium-hydrogen exchanger, vacuolar H+-ATPases and carbonic anhydrases are also involved in tumorigenesis of GC. Their pharmacological manipulation and gene silencing affect cellular behaviours, suggesting their potential as therapeutic targets for GC. Our studies indicate the intracellular Cl- concentration could act as a mediator of cellular signaling and control cell cycle progression in GC cells. Further, we demonstrate the cytocidal effects of hypotonic shock on GC cells, and indicate that the blockade of Cl- channels/transporters enhances these effects by inhibiting regulatory volume decrease. A deeper understanding of molecular mechanisms may lead to the discovery of these cellular physiological approaches as a novel therapeutic strategy for GC.

关键词： Gastric cancer Ion channels Water chan-nels intracellular pH intracellular chloride Osmolality

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NKCC1 and NKCC2:The pathogenetic role of cation-chloride cotransporters in hypertension

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Genes & Diseases 2015年第2期2卷 186-196页

作者： Sergei N.Orlov Svetlana V.Koltsova Leonid V.Kapilevich Svetlana V.Gusakova Nickolai O.Dulin Faculty of Biology M.V.Lomonosov Moscow State UniversityRussia Tomsk State University Russia Siberian State Medical University Russia University of Chicago Department of Medicine USA

This review summarizes the data on the functional significance of ubiquitous(NKCC1)and renal-specific(NKCC2)isoforms of electroneutral sodium,potassium and chloride *** carriers contribute to the pathogenesis of hypertension via regulation of intracellular chloride concentration in vascular smooth muscle and neuronal cells and via sensing chloride concentration in the renal tubular fluid,*** NKCC1 and NKCC2 are inhibited by furosemide and other high-ceiling diuretics widely used for attenuation of extracellular fluid ***,the chronic usage of these compounds for the treatment of hypertension and other volume-expanded disorders may have diverse side-effects due to suppression of myogenic response in microcirculatory beds.

关键词： Hypertension intracellular chloride Myogenic tone Neuronal cell NKCC cotransport Smooth muscle

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