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Shear Stress-Induced NO Production is Dependent on ATP Autocrine Signaling and Capacitative Calcium Entry
Journal article   Open access   Peer reviewed

Shear Stress-Induced NO Production is Dependent on ATP Autocrine Signaling and Capacitative Calcium Entry

Allison M. Andrews, Dov Jaron, Donald G. Buerk and Kenneth A. Barbee
Cellular and molecular bioengineering, v 7(4), pp 510-520
01 Dec 2014
PMID: 25386222
url
https://europepmc.org/articles/pmc4224574View
Accepted (AM) Open

Abstract

Biophysics Cell & Tissue Engineering Cell Biology Engineering Engineering, Biomedical Life Sciences & Biomedicine Science & Technology Technology
Flow-induced production of nitric oxide (NO) by endothelial cells plays a fundamental role in vascular homeostasis. However, the mechanisms by which shear stress activates NO production remain unclear due in part to limitations in measuring NO, especially under flow conditions. Shear stress elicits the release of ATP, but the relative contribution of autocrine stimulation by ATP to flow-induced NO production has not been established. Furthermore, the importance of calcium in shear stress-induced NO production remains controversial, and in particular the role of capacitive calcium entry (CCE) has yet to be determined. We have utilized our unique NO measurement device to investigate the role of ATP autocrine signaling and CCE in shear stress-induced NO production. We found that endogenously released ATP and downstream activation of purinergic receptors and CCE plays a significant role in shear stress-induced NO production. ATP-induced eNOS phophorylation under static conditions is also dependent on CCE. Inhibition of protein kinase C significantly inhibited eNOS phosphorylation and the calcium response. To our knowledge, we are the first to report on the role of CCE in the mechanism of acute shear stress-induced NO response. In addition, our work highlights the importance of ATP autocrine signaling in shear stress-induced NO production.

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20 citations in Scopus

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Web of Science research areas
Biophysics
Cell & Tissue Engineering
Cell Biology
Engineering, Biomedical
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