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Cortical Actin Nanodynamics Determines Nitric Oxide Release in Vascular Endothelium
The release of the main vasodilator nitric oxide (NO) by the endothelial NO synthase (eNOS) is a hallmark of endothelial function. We aim at elucidating the underlying mechanism how eNOS activity depends on cortical stiffness (К(cortex)) of living endothelial cells. It is hypothesized that cortical...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402397/ https://www.ncbi.nlm.nih.gov/pubmed/22844486 http://dx.doi.org/10.1371/journal.pone.0041520 |
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author | Fels, Johannes Jeggle, Pia Kusche-Vihrog, Kristina Oberleithner, Hans |
author_facet | Fels, Johannes Jeggle, Pia Kusche-Vihrog, Kristina Oberleithner, Hans |
author_sort | Fels, Johannes |
collection | PubMed |
description | The release of the main vasodilator nitric oxide (NO) by the endothelial NO synthase (eNOS) is a hallmark of endothelial function. We aim at elucidating the underlying mechanism how eNOS activity depends on cortical stiffness (К(cortex)) of living endothelial cells. It is hypothesized that cortical actin dynamics determines К(cortex) and directly influences eNOS activity. By combined atomic force microscopy and fluorescence imaging we generated mechanical and optical sections of single living cells. This approach allows the discrimination between К(cortex) and bulk cell stiffness (К(bulk)) and, additionally, the simultaneous analysis of submembranous actin web dynamics. We show that К(cortex) softens when cortical F-actin depolymerizes and that this shift from a gel-like stiff cortex to a soft G-actin rich layer, triggers the stiffness-sensitive eNOS activity. The results implicate that stiffness changes in the ∼100 nm phase of the submembranous actin web, without affecting К(bulk), regulate NO release and thus determines endothelial function. |
format | Online Article Text |
id | pubmed-3402397 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34023972012-07-27 Cortical Actin Nanodynamics Determines Nitric Oxide Release in Vascular Endothelium Fels, Johannes Jeggle, Pia Kusche-Vihrog, Kristina Oberleithner, Hans PLoS One Research Article The release of the main vasodilator nitric oxide (NO) by the endothelial NO synthase (eNOS) is a hallmark of endothelial function. We aim at elucidating the underlying mechanism how eNOS activity depends on cortical stiffness (К(cortex)) of living endothelial cells. It is hypothesized that cortical actin dynamics determines К(cortex) and directly influences eNOS activity. By combined atomic force microscopy and fluorescence imaging we generated mechanical and optical sections of single living cells. This approach allows the discrimination between К(cortex) and bulk cell stiffness (К(bulk)) and, additionally, the simultaneous analysis of submembranous actin web dynamics. We show that К(cortex) softens when cortical F-actin depolymerizes and that this shift from a gel-like stiff cortex to a soft G-actin rich layer, triggers the stiffness-sensitive eNOS activity. The results implicate that stiffness changes in the ∼100 nm phase of the submembranous actin web, without affecting К(bulk), regulate NO release and thus determines endothelial function. Public Library of Science 2012-07-23 /pmc/articles/PMC3402397/ /pubmed/22844486 http://dx.doi.org/10.1371/journal.pone.0041520 Text en Fels et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Fels, Johannes Jeggle, Pia Kusche-Vihrog, Kristina Oberleithner, Hans Cortical Actin Nanodynamics Determines Nitric Oxide Release in Vascular Endothelium |
title | Cortical Actin Nanodynamics Determines Nitric Oxide Release in Vascular Endothelium |
title_full | Cortical Actin Nanodynamics Determines Nitric Oxide Release in Vascular Endothelium |
title_fullStr | Cortical Actin Nanodynamics Determines Nitric Oxide Release in Vascular Endothelium |
title_full_unstemmed | Cortical Actin Nanodynamics Determines Nitric Oxide Release in Vascular Endothelium |
title_short | Cortical Actin Nanodynamics Determines Nitric Oxide Release in Vascular Endothelium |
title_sort | cortical actin nanodynamics determines nitric oxide release in vascular endothelium |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402397/ https://www.ncbi.nlm.nih.gov/pubmed/22844486 http://dx.doi.org/10.1371/journal.pone.0041520 |
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