BHK cells transfected with NCX3 are more resistant to hypoxia followed by reoxygenation than those transfected with NCX1 and NCX2: Possible relationship with mitochondrial membrane potential

Secondo, Agnese; Staiano, Rosaria Ilaria; Scorziello, Antonella; Sirabella, Rossana; Boscia, Francesca; Adornetto, Annagrazia; Valsecchi, Valeria; Molinaro, Pasquale; Canzoniero, Lorella M.T.; Renzo, Gianfranco Di; Annunziato, Lucio

doi:10.1016/j.ceca.2007.01.006

Cited by 95 publications

(127 citation statements)

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“…The latter showed similar sensitivity of their NCX activity to CB-DMB (Secondo A. et al, unpublished data). In addition, thapsigargin strongly potentiated the Ca 21 signals elicited by Na 1 -free solution [35]. Thus, the overall functional and pharmacological properties of the NCX activity characterized in human macrophages and monocytes appear to be similar to those in other cells and indicate that the exchanger can be involved in the generation of Ca 21 signals by operating in the reverse mode.…”

Section: Discussionmentioning

confidence: 69%

“…This suggests that the Ca 21 influx elicited by NCX activation in the reverse mode was probably counterbalanced by activation of sarco(endo)plasmic reticulum Ca 21 -ATPase (SERCA) [36]. To test this, HLM and monocytes were perfused with Na 1 -free medium in the presence of thapsigargin, a specific, irreversible inhibitor of SERCA [28,35]. Figure 4D shows that the Ca 21 influx elicited by Na 1 -free solution in HLM was greatly enhanced by thapsigargin and the signal was more persistent than in control cells in which this inhibitor was absent.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, it is conceivable that NCX cooperates with SERCA to restore Ca 21 gradients elicited by receptor-mediated stimuli. In this context, the role of NCX in macrophages and monocytes might be particularly important since NCX3, and partially NCX1, are not dependent on ATP for their function [35]. This means that NCX can contribute to maintaining [Ca 21 ] i homeostasis also in pathophysiological conditions such as tissue ischemia or anoxia in which ATP levels are reduced and the other Ca 21 buffering systems are impaired [2,35].…”

Section: Discussionmentioning

confidence: 99%

“…To verify that the Ca 21 signal induced by the Na 1 -free medium in HLM and monocytes was only due to the NCX activity, cells were preincubated (371C, 1 h) with the amiloride derivative 5-(N-4-chlorobenzyl)-20,40-dimethylbenzamil (CB-DMB) (10 mM) -a pan inhibitor of all three NCX isoforms [35,37] -before exposure to the Na 1 -free medium. CB-DMB completely blocked the Ca 21 influx elicited by Na 1 -free perfusion in HLM ( Fig.…”

Section: Effect Of Cb-dmb On the [Ca 21 ] I Increase Induced By Na 1 mentioning

confidence: 99%

“…At the end of each experiment, cell viability was assessed by trypan blue exclusion and was always greater than 95%. The cells remaining in the plates were lysed with 0.1% Triton X-100 for the determination of total cellular content of proteins and b-glucuronidase.Viability of cells treated with CB-DMB was evaluated as mitochondrial activity, determined by the MTT assay, as reported previously [35]. HLM and monocytes were incubated with CB-DMB (10 mM), 1% v/v Triton X-100 or medium alone for the time indicated.…”

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Expression and function of Na⁺/Ca²⁺ exchangers 1 and 3 in human macrophages and monocytes

et al. 2009

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The Na 1 /Ca 21 exchanger (NCX) is a membrane transporter that can switch Na 1 and Ca 21 in either direction to maintain the homeostasis of intracellular Ca 21 . Three isoforms (NCX1, NCX2, and NCX3) have been characterized in excitable cells, e.g. neurons and muscle cells. We examined the expression of these NCX isoforms in primary human lung macrophages (HLM) and blood monocytes. NCX1 and NCX3, but not NCX2, are expressed in HLM and monocytes at both mRNA and protein levels. Na 1 -free medium induced a significant increase in intracellular calcium concentration ([Ca 21 ] i ) in both cell types. This response was completely abolished by the NCX inhibitor 5-(N-4-chlorobenzyl)-20,40-dimethylbenzamil (CB-DMB). Moreover, inhibition of NCX activity during Ca 21 -signaling induced by histamine caused a delay in restoring baseline [Ca 21 ] i . Na 1 -free medium induced TNF-a expression and release in HLM comparable to that caused by LPS. TNF-a release induced by Na 1 -free medium was blocked by CB-DMB and greatly reduced by RNAi-mediated knockdown of NCX1. These results indicate that human macrophages and monocytes express NCX1 and NCX3 that operate in a bidirectional manner to restore [Ca 21 ] i , to generate Ca 21 -signals, and to induce TNF-a production. Therefore, NCX may contribute to regulate Ca 21 homeostasis and proinflammatory functions in human macrophages and monocytes.Key words: Ca 21 -signaling . Macrophages . Monocytes . Na 1 /Ca 21 exchanger IntroductionThe Na 1 /Ca 21 exchanger (NCX) is a plasma membrane protein involved in the homeostasis of intracellular Ca 21 [1]. NCX is a bidirectional ion transporter that catalyzes the exchange of Na 1 and Ca 21 depending on their electrochemical gradients [2]. Under physiological conditions, NCX's primary role is to extrude Ca 21 from cells using the Na 1 gradient across the cell membrane (forward mode of operation) [3]. However, in some cases it can contribute to the Ca 21 influx into the cells by working in the reverse mode (i.e. coupling Ca 21 influx with Na 1 efflux) [4][5][6].Three isoforms of NCX, NCX1, NCX2, and NCX3 have been cloned in mammals, outlining a multigene family whose members share a similar molecular structure [7]. NCX is modeled with nine transmembrane segments involved in ion transport and a long central cytoplasmic loop that has regulatory functions [8]. However, truncated forms lacking certain transmembrane segments, but still possessing NCX activity, have also been Eur. J. Immunol. 2009. 39: 1405-1418 DOI 10.1002 Leukocyte signaling 1405 described as the result of alternative splicing of the three genes [9][10][11]. NCX1 is largely predominant in mammalian tissues such as heart, brain, and kidney while the expression of NCX2 and NCX3 appears to be limited to the brain and skeletal muscle [7]. NCX is a key element regulating intracellular Ca 21 concentrations ([Ca 21 ] i ) in many excitable cells, including myocardiocytes, retinal rod photoreceptors, smooth muscle cells, and neurons [3]. Non-excitable cells such as renal epithelial ce...

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Section: Discussionmentioning

confidence: 69%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Effect Of Cb-dmb On the [Ca 21 ] I Increase Induced By Na 1 mentioning

confidence: 99%

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Expression and function of Na⁺/Ca²⁺ exchangers 1 and 3 in human macrophages and monocytes

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Mitochondrial Permeability Transition

Brustovetsky

2015

The Functions, Disease‐Related Dysfunctions, and Therapeutic Targeting of Neuronal Mitochondria

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Glial Na⁺‐dependent ion transporters in pathophysiological conditions

Boscia

Begum²,

Pignataro

et al. 2016

Glia

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Sodium dynamics are essential for regulating functional processes in glial cells. Indeed, glial Na+ signaling influences and regulates important glial activities, and plays a role in neuron-glia interaction under physiological conditions or in response to injury of the central nervous system (CNS). Emerging studies indicate that Na+ pumps and Na+-dependent ion transporters in astrocytes, microglia, and oligodendrocytes regulate Na+ homeostasis and play a fundamental role in modulating glial activities in neurological diseases. In this review, we first briefly introduced the emerging roles of each glial cell type in the pathophysiology of cerebral ischemia, Alzheimer’s disease, epilepsy, Parkinson’s disease, Amyotrophic Lateral Sclerosis, and myelin diseases. Then, we discussed the current knowledge on the main roles played by the different glial Na+-dependent ion transporters, including Na+/K+ ATPase, Na+/Ca2+ exchangers, Na+/H+ exchangers, Na+-K+-Cl− cotransporters, and Na+-HCO3− cotransporter in the pathophysiology of the diverse CNS diseases. We highlighted their contributions in cell survival, synaptic pathology, gliotransmission, pH homeostasis, and their role in glial activation, migration, gliosis, inflammation, and tissue repair processes. Therefore, this review summarizes the foundation work for targeting Na+-dependent ion transporters in glia as a novel strategy to control important glial activities associated with Na+ dynamics in different neurological disorders.

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BHK cells transfected with NCX3 are more resistant to hypoxia followed by reoxygenation than those transfected with NCX1 and NCX2: Possible relationship with mitochondrial membrane potential

Cited by 95 publications

References 49 publications

Expression and function of Na⁺/Ca²⁺ exchangers 1 and 3 in human macrophages and monocytes

Expression and function of Na⁺/Ca²⁺ exchangers 1 and 3 in human macrophages and monocytes

Mitochondrial Permeability Transition

Glial Na⁺‐dependent ion transporters in pathophysiological conditions

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BHK cells transfected with NCX3 are more resistant to hypoxia followed by reoxygenation than those transfected with NCX1 and NCX2: Possible relationship with mitochondrial membrane potential

Cited by 95 publications

References 49 publications

Expression and function of Na+/Ca2+ exchangers 1 and 3 in human macrophages and monocytes

Expression and function of Na+/Ca2+ exchangers 1 and 3 in human macrophages and monocytes

Mitochondrial Permeability Transition

Glial Na+‐dependent ion transporters in pathophysiological conditions

Contact Info

Product

Resources

About

Expression and function of Na⁺/Ca²⁺ exchangers 1 and 3 in human macrophages and monocytes

Expression and function of Na⁺/Ca²⁺ exchangers 1 and 3 in human macrophages and monocytes

Glial Na⁺‐dependent ion transporters in pathophysiological conditions