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The effect of xanthine oxidase and hypoxanthine on the permeability of red cells from patients with sickle cell anemia

Red cells from patients with sickle cell anemia (SCA) are under greater oxidative challenge than those from normal individuals. We postulated that oxidants generated by xanthine oxidase (XO) and hypoxanthine (HO) contribute to the pathogenesis of SCA through altering solute permeability. Sickling, a...

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Autores principales: Al Balushi, Halima W. M., Rees, David C., Brewin, John N., Hannemann, Anke, Gibson, John S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835498/
https://www.ncbi.nlm.nih.gov/pubmed/29504282
http://dx.doi.org/10.14814/phy2.13626
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author Al Balushi, Halima W. M.
Rees, David C.
Brewin, John N.
Hannemann, Anke
Gibson, John S.
author_facet Al Balushi, Halima W. M.
Rees, David C.
Brewin, John N.
Hannemann, Anke
Gibson, John S.
author_sort Al Balushi, Halima W. M.
collection PubMed
description Red cells from patients with sickle cell anemia (SCA) are under greater oxidative challenge than those from normal individuals. We postulated that oxidants generated by xanthine oxidase (XO) and hypoxanthine (HO) contribute to the pathogenesis of SCA through altering solute permeability. Sickling, activities of the main red cell dehydration pathways (P(sickle), Gardos channel, and KCl cotransporter [KCC]), and cell volume were measured at 100, 30, and 0 mmHg O(2), together with deoxygenation‐induced nonelectrolyte hemolysis. Unexpectedly, XO/HO mixtures had mainly inhibitory effects on sickling, P(sickle), and Gardos channel activities, while KCC activity and nonelectrolyte hemolysis were increased. Gardos channel activity was significantly elevated in red cells pharmacologically loaded with Ca(2+) using the ionophore A23187, consistent with an effect on the transport system per se as well as via Ca(2+) entry likely via the P(sickle) pathway. KCC activity is controlled by several pairs of conjugate protein kinases and phosphatases. Its activity, however, was also stimulated by XO/HO mixtures in red cells pretreated with N‐ethylmaleimide (NEM), which is thought to prevent regulation via changes in protein phosphorylation, suggesting that the oxidants formed could also have direct effects on this transporter. In the presence of XO/HO, red cell volume was better maintained in deoxygenated red cells. Overall, the most notable effect of XO/HO mixtures was an increase in red cell fragility. These findings increase our understanding of the effects of oxidative challenge in SCA patients and are relevant to the behavior of red cells in vivo.
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spelling pubmed-58354982018-03-07 The effect of xanthine oxidase and hypoxanthine on the permeability of red cells from patients with sickle cell anemia Al Balushi, Halima W. M. Rees, David C. Brewin, John N. Hannemann, Anke Gibson, John S. Physiol Rep Original Research Red cells from patients with sickle cell anemia (SCA) are under greater oxidative challenge than those from normal individuals. We postulated that oxidants generated by xanthine oxidase (XO) and hypoxanthine (HO) contribute to the pathogenesis of SCA through altering solute permeability. Sickling, activities of the main red cell dehydration pathways (P(sickle), Gardos channel, and KCl cotransporter [KCC]), and cell volume were measured at 100, 30, and 0 mmHg O(2), together with deoxygenation‐induced nonelectrolyte hemolysis. Unexpectedly, XO/HO mixtures had mainly inhibitory effects on sickling, P(sickle), and Gardos channel activities, while KCC activity and nonelectrolyte hemolysis were increased. Gardos channel activity was significantly elevated in red cells pharmacologically loaded with Ca(2+) using the ionophore A23187, consistent with an effect on the transport system per se as well as via Ca(2+) entry likely via the P(sickle) pathway. KCC activity is controlled by several pairs of conjugate protein kinases and phosphatases. Its activity, however, was also stimulated by XO/HO mixtures in red cells pretreated with N‐ethylmaleimide (NEM), which is thought to prevent regulation via changes in protein phosphorylation, suggesting that the oxidants formed could also have direct effects on this transporter. In the presence of XO/HO, red cell volume was better maintained in deoxygenated red cells. Overall, the most notable effect of XO/HO mixtures was an increase in red cell fragility. These findings increase our understanding of the effects of oxidative challenge in SCA patients and are relevant to the behavior of red cells in vivo. John Wiley and Sons Inc. 2018-03-04 /pmc/articles/PMC5835498/ /pubmed/29504282 http://dx.doi.org/10.14814/phy2.13626 Text en © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Al Balushi, Halima W. M.
Rees, David C.
Brewin, John N.
Hannemann, Anke
Gibson, John S.
The effect of xanthine oxidase and hypoxanthine on the permeability of red cells from patients with sickle cell anemia
title The effect of xanthine oxidase and hypoxanthine on the permeability of red cells from patients with sickle cell anemia
title_full The effect of xanthine oxidase and hypoxanthine on the permeability of red cells from patients with sickle cell anemia
title_fullStr The effect of xanthine oxidase and hypoxanthine on the permeability of red cells from patients with sickle cell anemia
title_full_unstemmed The effect of xanthine oxidase and hypoxanthine on the permeability of red cells from patients with sickle cell anemia
title_short The effect of xanthine oxidase and hypoxanthine on the permeability of red cells from patients with sickle cell anemia
title_sort effect of xanthine oxidase and hypoxanthine on the permeability of red cells from patients with sickle cell anemia
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835498/
https://www.ncbi.nlm.nih.gov/pubmed/29504282
http://dx.doi.org/10.14814/phy2.13626
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