Parallel Changes in Intracellular Water Volume and pH Induced by NH3/NH4+Exposure in Single Neuroblastoma Cells

Blanco, Víctor; Márquez, Martín S.; Álvarez-Leefmans, Francisco J.

doi:10.1159/000356624

Cited by 11 publications

(4 citation statements)

References 57 publications

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“…IL1β, IL6, TNFα and CRP were purchased from R&D Systems (Abingdon, Oxfordshire, UK), and were used as 10 ng/mL, as described previously [46][47][48]. Ammonium chloride was used at concentrations between 1 and 10 mM, as described previously [49][50][51][52][53].…”

Section: Methodsmentioning

confidence: 99%

Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial Cells

Regan

Mirczuk

Scudder

et al. 2021

Cells

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C-type natriuretic peptide (CNP) is the major natriuretic peptide of the central nervous system and acts via its selective guanylyl cyclase-B (GC-B) receptor to regulate cGMP production in neurons, astrocytes and endothelial cells. CNP is implicated in the regulation of neurogenesis, axonal bifurcation, as well as learning and memory. Several neurological disorders result in toxic concentrations of ammonia (hyperammonaemia), which can adversely affect astrocyte function. However, the relationship between CNP and hyperammonaemia is poorly understood. Here, we examine the molecular and pharmacological control of CNP in rat C6 glioma cells and rat GPNT brain endothelial cells, under conditions of hyperammonaemia. Concentration-dependent inhibition of C6 glioma cell proliferation by hyperammonaemia was unaffected by CNP co-treatment. Furthermore, hyperammonaemia pre-treatment (for 1 h and 24 h) caused a significant inhibition in subsequent CNP-stimulated cGMP accumulation in both C6 and GPNT cells, whereas nitric-oxide-dependent cGMP accumulation was not affected. CNP-stimulated cGMP efflux from C6 glioma cells was significantly reduced under conditions of hyperammonaemia, potentially via a mechanism involving changed in phosphodiesterase expression. Hyperammonaemia-stimulated ROS production was unaffected by CNP but enhanced by a nitric oxide donor in C6 cells. Extracellular vesicle production from C6 cells was enhanced by hyperammonaemia, and these vesicles caused impaired CNP-stimulated cGMP signalling in GPNT cells. Collectively, these data demonstrate functional interaction between CNP signalling and hyperammonaemia in C6 glioma and GPNT cells, but the exact mechanisms remain to be established.

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Section: Methodsmentioning

confidence: 99%

Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial Cells

Regan

Mirczuk

Scudder

et al. 2021

Cells

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“…

influx was increased in HSG cells upon acute Dex treatment, but was partially inhibited with long- lasting Dex treatment for 2 h (Figures 2C,D ). Part of

influx is mediated by NKCC1 (Blanco et al, 2013 ). Bumetanide (Bumeta) is an inhibitor of NKCC1.…”

Section: Resultsmentioning

confidence: 99%

Two Phase Modulation of NH4+ Entry and Cl−/HCO3- Exchanger in Submandibular Glands Cells by Dexmedetomidine

Lee

Park

et al. 2017

Front. Physiol.

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Dexmedetomidine (Dex), a highly selective α2-adrenoceptor agonist, attenuates inflammatory responses induced by lipopolysaccharide (LPS) and induces sedative and analgesic effects. Administration of Dex also reduces salivary secretion in human subjects and inhibits osmotic water permeability in rat cortical collecting ducts. However, little is known about the mechanisms underlying the effects of Dex on salivary glands fluid secretion. We demonstrated the α2-adrenoceptor expression in the basolateral membrane of mouse submandibular glands (SMG). To investigate fluid secretion upon treatment with Dex, we studied the effects of Dex on the activity of Na+-K+-2Cl− cotransporter1 (NKCC1) and Cl−/HCO3- exchange (CBE), and on downstream pro-inflammatory cytokine expression in isolated primary mouse SMG cells. Dex acutely increased CBE activity and NKCC1-mediated and independent NH4+ entry in SMG duct cells, and enhanced ductal fluid secretion in a sealed duct system. Dex showed differential effects on cholinergic/adrenergic stimulations and inflammatory mediators, histamine, and LPS, stimulations-induced Ca2+ in mouse SMG cells. Both, histamine- and LPS-induced intracellular Ca2+ increases were inhibited by Dex, whereas carbachol-stimulated Ca2+ signals were not. Long-lasting (2 h) treatment with Dex reduced CBE activity in SMG and in human submandibular glands (HSG) cells. Moreover, when isolated SMG cells were stimulated with Dex for 2 h, phosphodiesterase 4D (PDE4D) expression was enhanced. These results confirm the anti-inflammatory properties of Dex on LPS-mediated signaling. Further, Dex also inhibited mRNA expression of interleukin-6 and NADPH oxidase 4. The present study also showed that α2-adrenoceptor activation by Dex reduces salivary glands fluid secretion by increasing PDE4D expression, and subsequently reducing the concentration of cAMP. These findings reveal an interaction between the α2-adrenoceptor and PDE4D, which should be considered when using α2-adrenoceptor agonists as sedative or analgesics.

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“…A 2015 paper reported the behavior of HEK293 cells overexpressing a human KCC3a T991A-T1048A double mutant protein (Adragna, et al, 2015). Cell volume was measured using a well-established microscopic method based on fluorescent dye dilution (Blanco, Márquez & Alvarez-Leefmans, 2013; Lenart, Kintner, Shull & Sun, 2004). When wild-type HEK293 cells were exposed to a large 150 mOsM/Kg water osmotic shock, the cells increased their volume 3–4 times, then recovered their volume with a slope of 12% cell water volume recovery per min.…”

Section: Cell Volume Homeostasismentioning

confidence: 99%

Water Homeostasis and Cell Volume Maintenance and Regulation

Delpire

Gagnon

2018

Current Topics in Membranes

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From early unicellular organisms that formed in salty water environments to complex organisms that live on land away from water, cells have had to protect a homeostatic internal environment favorable to the biochemical reactions necessary for life. In this chapter, we will outline what steps were necessary to conserve the water within our cells and how mechanisms have evolved to maintain and regulate our cellular and organismal volume. We will first examine whole body water homeostasis and the relationship between kidney function, regulation of blood pressure, and blood filtration in the process of producing urine. We will then discuss how the composition of the lipid-rich bilayer affects its permeability to water and salts, and how the cell uses this differential to drive physiological and biochemical cellular functions. The capacity to maintain cell volume is vital to epithelial transport, neurotransmission, cell cycle, apoptosis, and cell migration. Finally, we will wrap up the chapter by discussing in some detail specific channels, cotransporters, and exchangers that have evolved to facilitate the movement of cations and anions otherwise unable to cross the lipid-rich bilayer and that are involved in maintaining or regulating cell volume.

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Parallel Changes in Intracellular Water Volume and pH Induced by NH₃/NH₄⁺Exposure in Single Neuroblastoma Cells

Cited by 11 publications

References 57 publications

Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial Cells

Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial Cells

Two Phase Modulation of NH4+ Entry and Cl−/HCO3- Exchanger in Submandibular Glands Cells by Dexmedetomidine

Water Homeostasis and Cell Volume Maintenance and Regulation

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