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

Frontiers in Physiology
Lennart KuckMichael J Simmonds

Abstract

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 act...Continue Reading

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Citations

Jan 29, 2020·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Ying-Hsuan TaiChih-Cherng Lu
Jun 25, 2020·American Journal of Physiology. Cell Physiology·Lennart KuckMichael J Simmonds
Jul 18, 2020·Clinical Hemorheology and Microcirculation·Daniel A BizjakMarijke Grau
Jan 13, 2021·Life·Jarod T HorobinMichael J Simmonds
Jul 28, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Lennart KuckMichael J Simmonds

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Methods Mentioned

BETA
Assay
electrophoresis

Software Mentioned

Prism
Image J
GraphPad

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