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On the effects of reactive oxygen species and nitric oxide on red blood cell deformability

On the effects of reactive oxygen species and nitric oxide on red blood cell deformability
On the effects of reactive oxygen species and nitric oxide on red blood cell deformability

The main function of red blood cells (RBCs) is the transport of respiratory gases along the vascular tree. To fulfill their task, RBCs are able to elastically deform in response to mechanical forces and, pass through the narrow vessels of the microcirculation. Decreased RBC deformability was observed in pathological conditions linked to increased oxidative stress or decreased nitric oxide (NO) bioavailability, like hypertension. Treatments with oxidants and with NO were shown to affect RBC deformability ex vivo, but the mechanisms underpinning these effects are unknown. In this study we investigate whether changes in intracellular redox status/oxidative stress or nitrosation reactions induced by reactive oxygen species (ROS) or NO may affect RBC deformability. In a case-control study comparing RBCs from healthy and hypertensive participants, we found that RBC deformability was decreased, and levels of ROS were increased in RBCs from hypertensive patients as compared to RBCs from aged-matched healthy controls, while NO levels in RBCs were not significantly different. To study the effects of oxidants on RBC redox state and deformability, RBCs from healthy volunteers were treated with increasing concentrations of tert-butylhydroperoxide (t-BuOOH). We found that high concentrations of t-BuOOH (≥1 mM) significantly decreased the GSH/GSSG ratio in RBCs, decreased RBC deformability and increased blood bulk viscosity. Moreover, RBCs from Nrf2 knockout (KO) mice, a strain genetically deficient in a number of antioxidant/reducing enzymes, were more susceptible to t-BuOOH-induced impairment in RBC deformability as compared to wild type (WT) mice. To study the role of NO in RBC deformability we treated RBC suspensions from human volunteers with NO donors and nitrosothiols and analyzed deformability of RBCs from mice lacking the endothelial NO synthase (eNOS). We found that NO donors induced S-nitrosation of the cytoskeletal protein spectrin, but did not affect human RBC deformability or blood bulk viscosity; moreover, under unstressed conditions RBCs from eNOS KO mice showed fully preserved RBC deformability as compared to WT mice. Pre-treatment of human RBCs with nitrosothiols rescued t-BuOOH-mediated loss of RBC deformability. Taken together, these findings suggest that NO does not affect RBC deformability per se, but preserves RBC deformability in conditions of oxidative stress.

Erythrocytes, Mechanotransduction, Nitric oxide synthase, Non-canonical function, RBC deformability, Reactive oxygen species, Thiols
1664-042X
1-14
Diederich, Lukas
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Suvorava, Tatsiana
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Sansone, Roberto
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Keller, T.C. Stevenson
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Barbarino, Frederik
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Sutton, Thomas R.
dbc4cb4f-cab0-46ee-b911-8945f50563cd
Kramer, Christian M.
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Lückstädt, Wiebke
a28f5d36-56fd-4c5a-9977-b82cabc40fbd
Isakson, Brant E.
d5518ad3-ee1a-4715-a6af-75b1b4342266
Gohlke, Holger
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Feelisch, Martin
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Kelm, Malte
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Cortese-Krott, Miriam M.
7dc9b44c-847c-4196-8866-a3cc0c1dc357
Diederich, Lukas
7323788c-6c8b-4514-9154-5219474b49e4
Suvorava, Tatsiana
94b506fa-15b0-4f1d-9310-b8d2e6c1cb07
Sansone, Roberto
eda52dc1-401d-4ba3-81a8-a3dca81199ea
Keller, T.C. Stevenson
b1f87cb2-2fca-41c3-bb38-b0f225214145
Barbarino, Frederik
b53ad146-43db-4a6e-8038-59fd1033ab0d
Sutton, Thomas R.
dbc4cb4f-cab0-46ee-b911-8945f50563cd
Kramer, Christian M.
36b6e166-bce9-462a-b000-e36da2e91ee3
Lückstädt, Wiebke
a28f5d36-56fd-4c5a-9977-b82cabc40fbd
Isakson, Brant E.
d5518ad3-ee1a-4715-a6af-75b1b4342266
Gohlke, Holger
77ea03f8-894e-44d8-8765-18110d89128b
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Kelm, Malte
db2bb062-32d7-4b50-9f65-8ba89ffa5f42
Cortese-Krott, Miriam M.
7dc9b44c-847c-4196-8866-a3cc0c1dc357

Diederich, Lukas, Suvorava, Tatsiana, Sansone, Roberto, Keller, T.C. Stevenson, Barbarino, Frederik, Sutton, Thomas R., Kramer, Christian M., Lückstädt, Wiebke, Isakson, Brant E., Gohlke, Holger, Feelisch, Martin, Kelm, Malte and Cortese-Krott, Miriam M. (2018) On the effects of reactive oxygen species and nitric oxide on red blood cell deformability. Frontiers in Physiology, 9 (MAY), 1-14, [332]. (doi:10.3389/fphys.2018.00332).

Record type: Article

Abstract

The main function of red blood cells (RBCs) is the transport of respiratory gases along the vascular tree. To fulfill their task, RBCs are able to elastically deform in response to mechanical forces and, pass through the narrow vessels of the microcirculation. Decreased RBC deformability was observed in pathological conditions linked to increased oxidative stress or decreased nitric oxide (NO) bioavailability, like hypertension. Treatments with oxidants and with NO were shown to affect RBC deformability ex vivo, but the mechanisms underpinning these effects are unknown. In this study we investigate whether changes in intracellular redox status/oxidative stress or nitrosation reactions induced by reactive oxygen species (ROS) or NO may affect RBC deformability. In a case-control study comparing RBCs from healthy and hypertensive participants, we found that RBC deformability was decreased, and levels of ROS were increased in RBCs from hypertensive patients as compared to RBCs from aged-matched healthy controls, while NO levels in RBCs were not significantly different. To study the effects of oxidants on RBC redox state and deformability, RBCs from healthy volunteers were treated with increasing concentrations of tert-butylhydroperoxide (t-BuOOH). We found that high concentrations of t-BuOOH (≥1 mM) significantly decreased the GSH/GSSG ratio in RBCs, decreased RBC deformability and increased blood bulk viscosity. Moreover, RBCs from Nrf2 knockout (KO) mice, a strain genetically deficient in a number of antioxidant/reducing enzymes, were more susceptible to t-BuOOH-induced impairment in RBC deformability as compared to wild type (WT) mice. To study the role of NO in RBC deformability we treated RBC suspensions from human volunteers with NO donors and nitrosothiols and analyzed deformability of RBCs from mice lacking the endothelial NO synthase (eNOS). We found that NO donors induced S-nitrosation of the cytoskeletal protein spectrin, but did not affect human RBC deformability or blood bulk viscosity; moreover, under unstressed conditions RBCs from eNOS KO mice showed fully preserved RBC deformability as compared to WT mice. Pre-treatment of human RBCs with nitrosothiols rescued t-BuOOH-mediated loss of RBC deformability. Taken together, these findings suggest that NO does not affect RBC deformability per se, but preserves RBC deformability in conditions of oxidative stress.

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fphys-09-00332
Available under License Creative Commons Attribution.
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Accepted/In Press date: 16 March 2018
e-pub ahead of print date: 11 May 2018
Keywords: Erythrocytes, Mechanotransduction, Nitric oxide synthase, Non-canonical function, RBC deformability, Reactive oxygen species, Thiols

Identifiers

Local EPrints ID: 424873
URI: http://eprints.soton.ac.uk/id/eprint/424873
ISSN: 1664-042X
PURE UUID: 8a64cfe4-812f-40c0-87f7-5cdb05362ddc
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 05 Oct 2018 11:51
Last modified: 26 Nov 2021 02:58

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Contributors

Author: Lukas Diederich
Author: Tatsiana Suvorava
Author: Roberto Sansone
Author: T.C. Stevenson Keller
Author: Frederik Barbarino
Author: Thomas R. Sutton
Author: Christian M. Kramer
Author: Wiebke Lückstädt
Author: Brant E. Isakson
Author: Holger Gohlke
Author: Martin Feelisch ORCID iD
Author: Malte Kelm
Author: Miriam M. Cortese-Krott

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