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Accepted (AM)Open Access (License Unspecified), Open
Journal article
TRPC channel-derived calcium fluxes differentially regulate ATP and flow-induced activation of eNOS
Nitric oxide, v 111, pp 1-13
01 Jun 2021
PMID: 33813098
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Endothelial dysfunction, characterised by impaired nitric oxide (NO) bioavailability, arises in response to a variety of cardiovascular risk factors and precedes atherosclerosis. NO is produced by tight regulation of endothelial nitric oxide synthase (eNOS) activity in response to vasodilatory stimuli. This regulation of eNOS is mediated in part by store-operated calcium entry (SOCE). We hypothesized that both ATP- and flow-induced eNOS activation are regulated by SOCE derived from Orai1 channels and members of the transient receptor potential canonical (TRPC) channel family. Bovine aortic endothelial cells (BAECs) were pre-treated with pharmacological inhibitors of TRPC channels and Orai1 to examine their effect on calcium signaling and eNOS activation in response to flow and ATP. The peak and sustained ATP-induced calcium signal and the resulting eNOS activation were attenuated by inhibition of TRPC3, which we found to be store operated. TRPC4 blockade reduced the transient peak in calcium concentration following ATP stimulation, but did not significantly reduce eNOS activity. Simultaneous TRPC3 & 4 inhibition reduced flow-induced NO production via alterations in phosphorylation-mediated eNOS activity. Inhibition of TRPC1/6 or Orai1 failed to lower ATP-induced calcium entry or eNOS activation. Our results suggest that TRPC3 is a store-operated channel in BAECs and is the key regulator of ATP-induced eNOS activation, whereas flow stimulation also recruits TRPC4 into the pathway for the synthesis of NO.
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Details
- Title
- TRPC channel-derived calcium fluxes differentially regulate ATP and flow-induced activation of eNOS
- Creators
- Tenderano T. Muzorewa - Drexel UniversityDonald G. Buerk - Drexel UniversityDov Jaron - Drexel UniversityKenneth A. Barbee - Drexel University
- Publication Details
- Nitric oxide, v 111, pp 1-13
- Publisher
- Elsevier
- Number of pages
- 13
- Grant note
- U01HL116256 / National Heart, Lung and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; [Retired Faculty]
- Web of Science ID
- WOS:000655728300001
- Scopus ID
- 2-s2.0-85104069236
- Other Identifier
- 991019168163104721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology