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dc.contributor.authorKuck, Lennart
dc.contributor.authorGrau, Marijke
dc.contributor.authorBloch, Wilhelm
dc.contributor.authorSimmonds, Michael J
dc.date.accessioned2019-10-30T04:23:01Z
dc.date.available2019-10-30T04:23:01Z
dc.date.issued2019
dc.identifier.issn1664-042X
dc.identifier.doi10.3389/fphys.2019.00036
dc.identifier.urihttp://hdl.handle.net/10072/388764
dc.description.abstractThe cellular deformability of red blood cells (RBC) is exceptional among mammalian cells and facilitates nutrient delivery throughout the microcirculation; however, this physical property is negatively impacted by oxidative stress. It remains unresolved whether the molecular determinants of cellular deformability - which in the contemporary model of RBC are increasingly recognized - are sensitive to free radicals. Moreover, given cellular deformability has recently been demonstrated to increase following exposure to specific doses of mechanical stimulation, the potential for using shear “conditioning” as a novel method to reverse free-radical induced impairment of cell mechanics is of interest. We thus designed a series of experiments that explored the effects of intracellular superoxide (O2-) generation on the deformability of RBC and also activation of pivotal molecular pathways known to regulate cell mechanics - i.e., PI3K/Akt kinase and RBC nitric oxide synthase (NOS). In addition, RBC exposed to O2- were conditioned with specific shear stresses, prior to evaluation of cellular deformability and activation of PI3K/Akt kinase and RBC-NOS. Intracellular generation of O2- decreased phosphorylation of RBC-NOS at its primary activation site (Ser1177) (p < 0.001), while phosphorylation of Akt kinase at its active residue (Ser473) was also diminished (p < 0.001). Inactivation of these enzymes following O2- exposure occurred in tandem with decreased RBC deformability. Shear conditioning significantly improved cellular deformability, even in RBC previously exposed to O2-. The improvement in cellular deformability may have been the result of enhanced molecular signaling, given RBC-NOS phosphorylation in RBC exposed to O2- was restored following shear conditioning. Impaired RBC deformability induced by intracellular O2-may be due, in part, to impaired activation of PI3K/Akt, and downstream signaling with RBC-NOS. These findings may shed light on improved circulatory health with targeted promotion of blood flow (e.g., exercise training), and may prove fruitful in future development of blood-contacting devices.
dc.description.peerreviewedYes
dc.description.sponsorshipGold Coast Hospital and Health Service
dc.languageEnglish
dc.language.isoeng
dc.publisherFrontiers Research Foundation
dc.publisher.placeSwitzerland
dc.relation.ispartofpagefrom36: 1
dc.relation.ispartofpageto36: 9
dc.relation.ispartofissueFEB
dc.relation.ispartofjournalFrontiers in Physiology
dc.relation.ispartofvolume10
dc.subject.fieldofresearchZoology
dc.subject.fieldofresearchMedical physiology
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchcode3109
dc.subject.fieldofresearchcode3208
dc.subject.fieldofresearchcode3101
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordshemorheology
dc.subject.keywordsshear conditioning
dc.titleShear Stress Ameliorates Superoxide Impairment to Erythrocyte Deformability With Concurrent Nitric Oxide Synthase Activation
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationKuck, L; Grau, M; Bloch, W; Simmonds, MJ, Shear Stress Ameliorates Superoxide Impairment to Erythrocyte Deformability With Concurrent Nitric Oxide Synthase Activation, Frontiers in Physiology, 2019, 10 (FEB), pp. 36: 1-36: 9
dcterms.dateAccepted2019-01-14
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.date.updated2019-10-25T05:24:43Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2019 Kuck, Grau, Bloch and Simmonds. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
gro.hasfulltextFull Text
gro.griffith.authorSimmonds, Michael J.
gro.griffith.authorKuck, Lennart L.


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