Cystic fibrosis transmembrane conductance regulator in human and mouse red blood cell membranes and its interaction with ecto‐apyrase

Sterling, Kenneth; Shah, Sanjiv; Kim, Ronald J.; Johnston, Nicholas; Salikhova, Anna Y.; Abraham, Edward

doi:10.1002/jcb.20017

Cited by 26 publications

(16 citation statements)

References 50 publications

(65 reference statements)

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“…Recently, it was shown that CFTR protein is present in erythrocyte membranes of both healthy humans and humans with cystic fibrosis (1,32). In addition, it was reported that human erythroblasts contain CFTR mRNA (37).…”

Section: Discussionmentioning

confidence: 99%

Erythrocytes of humans with cystic fibrosis fail to stimulate nitric oxide synthesis in isolated rabbit lungs

Liang¹,

Stephenson²,

Lonigro³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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Erythrocytes (red blood cells) of either rabbits or healthy humans are required to demonstrate the participation of nitric oxide (NO) in the regulation of pulmonary vascular resistance in the isolated rabbit lung. The property of the erythrocyte that is responsible for the stimulation of NO synthesis was reported to be the ability to release ATP in response to physiological stimuli, including deformation. Moreover, a signal transduction pathway that relates mechanical deformation of erythrocytes to ATP release has been described, and the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is a component, i.e., erythrocytes of individuals with CF do not release ATP in response to deformation. Here, we investigated the hypothesis that, in contrast to those of healthy humans, erythrocytes of humans with CF fail to stimulate endogenous NO synthesis in the isolated rabbit lung. We report that CFTR is a component of the membranes of both rabbit and human erythrocytes. The addition of the NO synthase inhibitor Nω-nitro-l-arginine methyl ester (l-NAME, 100 μM) produced increases in vascular resistance in isolated rabbit lungs perfused with physiological salt solution (PSS) containing erythrocytes of healthy humans, but l-NAME was without effect when the lungs were perfused with PSS alone or PSS containing erythrocytes of CF patients. These results provide support for the hypothesis that, in CF, a defect in ATP release from erythrocytes could lead to decreased endogenous pulmonary NO synthesis and contribute to pulmonary hypertension.

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Section: Discussionmentioning

confidence: 99%

Erythrocytes of humans with cystic fibrosis fail to stimulate nitric oxide synthesis in isolated rabbit lungs

Liang¹,

Stephenson²,

Lonigro³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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“…Co-immunoprecipitation data suggest that NTPDase can be associated with cystic fibrosis transmembrane regulator in human and mouse red blood cell membranes [162]. The interaction between the two proteins might positively affect ATP transport and extracellular hydrolysis [163].…”

Section: Protein Interactionsmentioning

confidence: 99%

Cellular function and molecular structure of ecto-nucleotidases

Zimmermann

Zebisch

Sträter

2012

Purinergic Signalling

879

922

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Ecto-nucleotidases play a pivotal role in purinergic signal transmission. They hydrolyze extracellular nucleotides and thus can control their availability at purinergic P2 receptors. They generate extracellular nucleosides for cellular reuptake and salvage via nucleoside transporters of the plasma membrane. The extracellular adenosine formed acts as an agonist of purinergic P1 receptors. They also can produce and hydrolyze extracellular inorganic pyrophosphate that is of major relevance in the control of bone mineralization. This review discusses and compares four major groups of ectonucleotidases: the ecto-nucleoside triphosphate diphosphohydrolases, ecto-5′-nucleotidase, ecto-nucleotide pyrophosphatase/phosphodiesterases, and alkaline phosphatases. Only recently and based on crystal structures, detailed information regarding the spatial structures and catalytic mechanisms has become available for members of these four ecto-nucleotidase families. This permits detailed predictions of their catalytic mechanisms and a comparison between the individual enzyme groups. The review focuses on the principal biochemical, cell biological, catalytic, and structural properties of the enzymes and provides brief reference to tissue distribution, and physiological and pathophysiological functions.

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“…The fate and half-life of extracellular nucleotides is determined by numerous nucleotide-metabolizing ecto-enzymes such as CD38 and CD39, many of which are expressed by erythrocytes (53,54). One should, therefore, expect that ultrasonication of erythrocytes would expose the released NAD ϩ and ATP to nucleotide-degrading enzymes.…”

Section: The P2x 7 -Inducing Activities In Erythrocyte Lysates Fade Umentioning

confidence: 99%

NAD+ and ATP Released from Injured Cells Induce P2X7-Dependent Shedding of CD62L and Externalization of Phosphatidylserine by Murine T Cells

Scheuplein

Schwarz²,

Adriouch

et al. 2009

The Journal of Immunology

114

136

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Extracellular NAD+ and ATP trigger the shedding of CD62L and the externalization of phosphatidylserine on murine T cells. These events depend on the P2X7 ion channel. Although ATP acts as a soluble ligand to activate P2X7, gating of P2X7 by NAD+ requires ecto-ADP-ribosyltransferase ART2.2-catalyzed transfer of the ADP-ribose moiety from NAD+ onto Arg125 of P2X7. Steady-state concentrations of NAD+ and ATP in extracellular compartments are highly regulated and usually are well below the threshold required for activating P2X7. The goal of this study was to identify possible endogenous sources of these nucleotides. We show that lysis of erythrocytes releases sufficient levels of NAD+ and ATP to induce activation of P2X7. Dilution of erythrocyte lysates or incubation of lysates at 37°C revealed that signaling by ATP fades more rapidly than that by NAD+. We further show that the routine preparation of primary lymph node and spleen cells induces the release of NAD+ in sufficient concentrations for ART2.2 to ADP-ribosylate P2X7, even at 4°C. Gating of P2X7 occurs when T cells are returned to 37°C, rapidly inducing CD62L-shedding and PS-externalization by a substantial fraction of the cells. The “spontaneous” activation of P2X7 during preparation of primary T cells could be prevented by i.v. injection of either the surrogate ART substrate etheno-NAD or ART2.2-inhibitory single domain Abs 10 min before sacrificing mice.

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Cystic fibrosis transmembrane conductance regulator in human and mouse red blood cell membranes and its interaction with ecto‐apyrase

Cited by 26 publications

References 50 publications

Erythrocytes of humans with cystic fibrosis fail to stimulate nitric oxide synthesis in isolated rabbit lungs

Erythrocytes of humans with cystic fibrosis fail to stimulate nitric oxide synthesis in isolated rabbit lungs

Cellular function and molecular structure of ecto-nucleotidases

NAD+ and ATP Released from Injured Cells Induce P2X7-Dependent Shedding of CD62L and Externalization of Phosphatidylserine by Murine T Cells

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