scholarly journals Role of the Cation-Chloride-Cotransporters in Cardiovascular Disease

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2293 ◽  
Author(s):  
Nur Farah Meor Azlan ◽  
Jinwei Zhang
Keyword(s):  
Cardiovascular Disease ◽  
Potassium Chloride ◽  
Genetic Disorders ◽  
Ion Homeostasis ◽  
Cell Volume Regulation ◽  
Renal Cells ◽  
Sodium Potassium ◽  
Physiological Processes ◽  
Cation Chloride Cotransporters

The SLC12 family of cation-chloride-cotransporters (CCCs) is comprised of potassium chloride cotransporters (KCCs), which mediate Cl− extrusion and sodium-potassium chloride cotransporters (N[K]CCs), which mediate Cl− loading. The CCCs play vital roles in cell volume regulation and ion homeostasis. The functions of CCCs influence a variety of physiological processes, many of which overlap with the pathophysiology of cardiovascular disease. Although not all of the cotransporters have been linked to Mendelian genetic disorders, recent studies have provided new insights into their functional role in vascular and renal cells in addition to their contribution to cardiovascular diseases. Particularly, an imbalance in potassium levels promotes the pathogenesis of atherosclerosis and disturbances in sodium homeostasis are one of the causes of hypertension. Recent findings suggest hypothalamic signaling as a key signaling pathway in the pathophysiology of hypertension. In this review, we summarize and discuss the role of CCCs in cardiovascular disease with particular emphasis on knowledge gained in recent years on NKCCs and KCCs.

scholarly journals Role of the Cation-chloride-cotransporters in Cardiovascular Disease

2020 ◽  
Author(s):  
Nur Farah Meor Azlan ◽  
Jinwei Zhang
Keyword(s):  
Cardiovascular Disease ◽  
Functional Role ◽  
Genetic Disorders ◽  
Ion Homeostasis ◽  
Cell Volume Regulation ◽  
Renal Cells ◽  
Sodium Homeostasis ◽  
Physiological Processes ◽  
Cation Chloride Cotransporters

The SLC12 family of cation-chloride-cotransporters (CCCs), comprising potassium chloride cotransporters (KCCs)-mediated Cl- extrusion relative to sodium chloride cotransporters (NKCCs)-mediated Cl- loading, play vital roles in cell volume regulation and ion homeostasis. These functions of the CCCs influence a variety of physiological processes, many of which overlap with the pathophysiology of cardiovascular disease. Although not all of the cotransporters have been linked to Mendelian genetic disorders, recent studies have provided new insights into their functional role in vascular and renal cells along with their contribution to cardiovascular diseases. Particularly, an imbalance in potassium levels promote the pathogenesis of atherosclerosis and disturbances in sodium homeostasis are one of the causes of hypertension. Recent findings even suggest hypothalamic signalling as a key signalling pathway in the pathophysiology of hypertension. In this review, we summarize and discuss the role of CCCs in cardiovascular disease with particular emphasis on knowledge gained in recent years on NKCCs and KCCs.

scholarly journals Fluorinated Mannosides Inhibit Cellular Fucosylation.

2020 ◽  
Author(s):  
Johan Pijnenborg ◽  
Emiel Rossing ◽  
Marek Noga ◽  
Willem Titulaer ◽  
Raisa Veizaj ◽  
...  
Keyword(s):  
Mammalian Cell ◽  
De Novo ◽  
Genetic Disorders ◽  
Living Cells ◽  
Aberrant Expression ◽  
Physiological Processes ◽  
Cancer Inflammation ◽  
Mannose Derivatives ◽  
Potential Therapeutics

Fucose sugars are expressed on mammalian cell membranes as part of glycoconjugates and mediates essential physiological processes. The aberrant expression of fucosylated glycans has been linked to pathologies such as cancer, inflammation, infection, and genetic disorders. Tools to modulate fucose expression on living cells are needed to elucidate the biological role of fucose sugars and the development of potential therapeutics. Herein, we report a novel class of fucosylation inhibitors directly targeting de novo GDP-fucose biosynthesis. We demonstrate that cell permeable fluorinated mannoside 1-phosphate derivatives (Fucotrim I & II) are metabolic prodrugs that are metabolized to their respective GDP-mannose derivatives and efficiently inhibit cellular fucosylation.

Actin dynamics as critical ion channel regulator: ENaC and Piezo in focus

2021 ◽  
Author(s):  
Elena A. Morachevskaya ◽  
Anastasia V. Sudarikova
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Dynamic Balance ◽  
Cell Volume Regulation ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Actin Assembly ◽  
Excitable Cells ◽  
Physiological Processes

Ion channels in plasma membrane play a principal role in different physiological processes, including cell volume regulation, signal transduction and modulation of membrane potential in living cells. Actin-based cytoskeleton, which exists in a dynamic balance between monomeric and polymeric forms (globular and fibrillar actin), can be directly or indirectly involved in various cellular responses including modulation of ion channel activity. In this mini-review, we present an overview of the role of submembranous actin dynamics in the regulation of ion channels in excitable and non-excitable cells. Special attention is focused on the important data about the involvement of actin assembly/disassembly and some actin-binding proteins in the control of the Epithelial Na+ Channel (ENaC) and mechanosensitive Piezo channels whose integral activity has potential impact on membrane transport and multiple coupled cellular reactions. Growing evidence suggests that actin elements of the cytoskeleton can represent a "converging point" of various signaling pathways modulating the activity of ion transport proteins in cell membranes.

scholarly journals The Movement of Solutes Across the Epithelium of the Ducts and Cisterns in the Mammary Gland of the Ewe

1965 ◽  
Vol 18 (5) ◽  
pp. 1035 ◽  
Author(s):  
DDS Mackenzie ◽  
AK Lascelles
Keyword(s):  
Mammary Gland ◽  
Water Absorption ◽  
Potassium Chloride ◽  
Chloride Ions ◽  
Rate Of Change ◽  
Milk Secretion ◽  
Sodium Potassium ◽  
Lactose Concentration

The role of the cisterns and large ducts in the overall process of milk secretion has been studied in experiments which have been carried out to determine the change in composition of solutions injected into the mammary gland cisterns of lactating and dry ewes. These solutions contained electrolytes, lactose, and a marker substance and were allowed to remain in the gland for periods of up to 4 hr. The concentration of sodium, potassium, chloride, and lactose in the solution injected into lactating glands approached with time that in milk. The data indicated that the rate of change in concentration of sodium, potassium, and chloride was more rapid than could be accounted for by the mixing of the injected solution with milk from the ducts. Sodium, potassium, and chloride ions were secreted into solutions in which the concentrations of these ions were lower than those in milk and sodium and chloride ions were absorbed from solutions in which their concentration was higher than that in milk. Water absorption occurred from the solutions containing sodium and chloride ata higher concentration than that in milk. In the dry gland the composition of the solutions injected approached with time that of involution secretion which has a higher sodium and chloride and lower potassium and lactose concentration than normal milk. Lactose was absorbed from dry glands but not from the lactating glands.

Cryo-EM structures of the human cation-chloride cotransporter KCC1

Science ◽  
2019 ◽  
Vol 366 (6464) ◽  
pp. 505-508 ◽  
Author(s):  
Si Liu ◽  
Shenghai Chang ◽  
Binming Han ◽  
Lingyi Xu ◽  
Mingfeng Zhang ◽  
...  
Keyword(s):  
Ion Transport ◽  
Potassium Chloride ◽  
Volume Regulation ◽  
Cell Volume Regulation ◽  
Aminobutyric Acid ◽  
Computational Studies ◽  
Transport Activity ◽  
Cryo Electron Microscopy ◽  
Cation Chloride Cotransporters ◽  
Functional Analyses

Cation-chloride cotransporters (CCCs) mediate the coupled, electroneutral symport of cations with chloride across the plasma membrane and are vital for cell volume regulation, salt reabsorption in the kidney, and γ-aminobutyric acid (GABA)–mediated modulation in neurons. Here we present cryo–electron microscopy (cryo-EM) structures of human potassium-chloride cotransporter KCC1 in potassium chloride or sodium chloride at 2.9- to 3.5-angstrom resolution. KCC1 exists as a dimer, with both extracellular and transmembrane domains involved in dimerization. The structural and functional analyses, along with computational studies, reveal one potassium site and two chloride sites in KCC1, which are all required for the ion transport activity. KCC1 adopts an inward-facing conformation, with the extracellular gate occluded. The KCC1 structures allow us to model a potential ion transport mechanism in KCCs and provide a blueprint for drug design.

scholarly journals Fluorinated rhamnosides inhibit cellular fucosylation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Johan F. A. Pijnenborg ◽  
Emiel Rossing ◽  
Jona Merx ◽  
Marek J. Noga ◽  
Willem H. C. Titulaer ◽  
...  
Keyword(s):  
Mammalian Cell ◽  
De Novo ◽  
Genetic Disorders ◽  
Living Cells ◽  
Aberrant Expression ◽  
Physiological Processes ◽  
Cancer Inflammation ◽  
Mannose Derivatives ◽  
Potential Therapeutics

AbstractThe sugar fucose is expressed on mammalian cell membranes as part of glycoconjugates and mediates essential physiological processes. The aberrant expression of fucosylated glycans has been linked to pathologies such as cancer, inflammation, infection, and genetic disorders. Tools to modulate fucose expression on living cells are needed to elucidate the biological role of fucose sugars and the development of potential therapeutics. Herein, we report a class of fucosylation inhibitors directly targeting de novo GDP-fucose biosynthesis via competitive GMDS inhibition. We demonstrate that cell permeable fluorinated rhamnose 1-phosphate derivatives (Fucotrim I & II) are metabolic prodrugs that are metabolized to their respective GDP-mannose derivatives and efficiently inhibit cellular fucosylation.

scholarly journals Fluorinated Mannosides Inhibit Cellular Fucosylation.

2020 ◽  
Author(s):  
Johan Pijnenborg ◽  
Emiel Rossing ◽  
Marek Noga ◽  
Willem Titulaer ◽  
Raisa Veizaj ◽  
...  
Keyword(s):  
Mammalian Cell ◽  
De Novo ◽  
Genetic Disorders ◽  
Living Cells ◽  
Aberrant Expression ◽  
Physiological Processes ◽  
Cancer Inflammation ◽  
Mannose Derivatives ◽  
Potential Therapeutics

Fucose sugars are expressed on mammalian cell membranes as part of glycoconjugates and mediates essential physiological processes. The aberrant expression of fucosylated glycans has been linked to pathologies such as cancer, inflammation, infection, and genetic disorders. Tools to modulate fucose expression on living cells are needed to elucidate the biological role of fucose sugars and the development of potential therapeutics. Herein, we report a novel class of fucosylation inhibitors directly targeting de novo GDP-fucose biosynthesis. We demonstrate that cell permeable fluorinated mannoside 1-phosphate derivatives (Fucotrim I & II) are metabolic prodrugs that are metabolized to their respective GDP-mannose derivatives and efficiently inhibit cellular fucosylation.

Sign in / Sign up

Export Citation Format

Share Document