Recovery time course of erythrocyte deformability following exposure to shear is dependent upon conditioning shear stress

Kuck, Lennart; Grau, Marijke; Simmonds, Michael J.

doi:10.3233/bir-17151

Cited by 18 publications

(11 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Experiment Two was designed to interrogate whether physiological magnitudes of shear exposure could recover, atleast in part, some of the impaired mechanical properties of RBC that had been previously exposed to free radicals. It was hypothesized that shear exposure within the physiological range would stimulate RBC-NOS phosphorylation at Ser 1177 , and therefore increase cellular deformability despite the prior oxidative “damage.” Mechanical stimulation of RBC significantly increased cell deformability by ∼18% ( p < 0.01, Figure 4) and increased phosphorylation of RBC-NOS ( p < 0.01, Figure 5), confirming previous reports (Ulker et al, 2011; Kuck et al, 2018). The current observations extend these findings, providing evidence that mechanical stimulation of RBC is also effective at improving cellular deformability in cells exposed to O 2 - (Figure 4).…”

Section: Discussionsupporting

confidence: 90%

“…Cells were inserted into a 300 μm gap between the cylinders; the outer cylinder (cup) rotated around the inner cylinder (bob) at a discrete velocity (shear rate), which was adjusted to generate the desired shear stress. The selected combinations of shear stress-exposure duration have been previously reported to consistently trigger a significant improvement in cellular deformability (Kuck et al, 2018); these were confirmed in the present study during pilot testing. Samples sheared using the cup-and-bob system were analyzed immediately for cellular deformability.…”

Section: Methodssupporting

confidence: 86%

See 1 more Smart Citation

Shear Stress Ameliorates Superoxide Impairment to Erythrocyte Deformability With Concurrent Nitric Oxide Synthase Activation

et al. 2019

Self Cite

View full text Add to dashboard Cite

The 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.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Methodssupporting

confidence: 86%

Shear Stress Ameliorates Superoxide Impairment to Erythrocyte Deformability With Concurrent Nitric Oxide Synthase Activation

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recent studies of RBC responses to shear stimuli (within physiological, subhaemolytic and haemolytic domains) have predominantly utilised whole blood that contains cell mixtures of all physiological ages. [15][16][17][18][19][20][21] While being highly relevant to in vivo blood composition, elucidation of the differential cell response to mechanical stresses of aged and young cells thus would be of value, particularly in the case of transfusion products; blood products may age ex vivo without replenishment from cell turnover, which is likely to skew these products towards older cell types that may be more susceptible to haemolyse in high shear environments (e.g. rotary blood pumps).…”

Section: Introductionmentioning

confidence: 99%

Susceptibility of density-fractionated erythrocytes to subhaemolytic mechanical shear stress

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…The biophysical interpretation is complicated with “cross-talks” of signaling systems in RBC, especially between AC-cascade and calcium signaling. Alterations of Ca 2+ -influx in RBC under application of shear stress are reported in several works and according to the recent data, this process reflects the response to mechanosensitive Piezo1 receptor stimulation (Cahalan et al, 2015; Kuck et al, 2018). This effect may be responsible for the EC50 shift in case of db-cAMP as it stimulates overall cAMP-dependent protein kinase activity in the cell, which is highly sensitive to cytosolic calcium (Rasmussen and Barrett, 1984).…”

Section: Discussionmentioning

confidence: 81%

The Effects of Different Signaling Pathways in Adenylyl Cyclase Stimulation on Red Blood Cells Deformability

et al. 2019

View full text Add to dashboard Cite

Signaling pathways of red blood cells’ (RBCs) micromechanics regulation, which are responsible for maintaining microcirculation, constitute an important property of RBC physiology. Selective control over these processes may serve as an indispensable tool for correction of hemorheological disorders, which accompany a number of systemic diseases (diabetes mellitus I&II, arterial hypertension, malaria, etc.). Activation of certain pathways involving adenylyl cyclase may provide fast adaptive regulation of RBC deformability (RBC-D). However the specific molecular conditions of intracellular signal transduction in mediating RBC microrheological properties at adenylyl cyclase stimulation remain unclear. In this paper, we present the results of the in vitro study of the effects of different signaling pathways in adenylyl cyclase stimulation on RBC-D. We studied (1) the direct stimulation of adenylyl cyclase with forskolin; (2) non-selective adrenoreceptor stimulation with epinephrine; (3) β2-adrenoreceptor agonist metaproterenol; (4) membrane-permeable analog of cAMP (dibutyryl-cAMP). Using laser ektacytometry, we observed a concentration-dependent increase in RBC-D for all studied effectors. The EC50 values for each substance were estimated to be in the range of 1–100 μM depending on the shear stress applied to the RBC suspension. The results can serve as an evidence of adenylyl cyclase signaling cascade involvement in the regulation of RBC micromechanical properties presenting a complex molecular pathway for fast increase of microcirculation efficiency in case of corresponding physiologic metabolic demands of the organism, e.g., during stress or physical activity. Further studies of this molecular system will reveal new knowledge which may improve the quality of medical treatment of hemorheological disorders.

show abstract

Recovery time course of erythrocyte deformability following exposure to shear is dependent upon conditioning shear stress

Abstract: Specific shear conditioning results in either temporarily increased cell deformability, or a less reversible decrease of RBC deformability.

Cited by 18 publications

References 28 publications

Shear Stress Ameliorates Superoxide Impairment to Erythrocyte Deformability With Concurrent Nitric Oxide Synthase Activation

Shear Stress Ameliorates Superoxide Impairment to Erythrocyte Deformability With Concurrent Nitric Oxide Synthase Activation

Susceptibility of density-fractionated erythrocytes to subhaemolytic mechanical shear stress

The Effects of Different Signaling Pathways in Adenylyl Cyclase Stimulation on Red Blood Cells Deformability

Contact Info

Product

Resources

About