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Direct Regulation of Striated Muscle Myosins by Nitric Oxide and Endogenous Nitrosothiols
BACKGROUND: Nitric oxide (NO) has long been recognized to affect muscle contraction [1], both through activation of guanylyl cyclase and through modification of cysteines in proteins to yield S-nitrosothiols. While NO affects the contractile apparatus directly, the identities of the target myofibril...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2887846/ https://www.ncbi.nlm.nih.gov/pubmed/20585450 http://dx.doi.org/10.1371/journal.pone.0011209 |
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author | Evangelista, Alicia M. Rao, Vijay S. Filo, Ashley R. Marozkina, Nadzeya V. Doctor, Allan Jones, David R. Gaston, Benjamin Guilford, William H. |
author_facet | Evangelista, Alicia M. Rao, Vijay S. Filo, Ashley R. Marozkina, Nadzeya V. Doctor, Allan Jones, David R. Gaston, Benjamin Guilford, William H. |
author_sort | Evangelista, Alicia M. |
collection | PubMed |
description | BACKGROUND: Nitric oxide (NO) has long been recognized to affect muscle contraction [1], both through activation of guanylyl cyclase and through modification of cysteines in proteins to yield S-nitrosothiols. While NO affects the contractile apparatus directly, the identities of the target myofibrillar proteins remain unknown. Here we report that nitrogen oxides directly regulate striated muscle myosins. PRINCIPAL FINDINGS: Exposure of skeletal and cardiac myosins to physiological concentrations of nitrogen oxides, including the endogenous nitrosothiol S-nitroso-L-cysteine, reduced the velocity of actin filaments over myosin in a dose-dependent and oxygen-dependent manner, caused a doubling of force as measured in a laser trap transducer, and caused S-nitrosylation of cysteines in the myosin heavy chain. These biomechanical effects were not observed in response to S-nitroso-D-cysteine, demonstrating specificity for the naturally occurring isomer. Both myosin heavy chain isoforms in rats and cardiac myosin heavy chain from human were S-nitrosylated in vivo. SIGNIFICANCE: These data show that nitrosylation signaling acts as a molecular “gear shift” for myosin—an altogether novel mechanism by which striated muscle and cellular biomechanics may be regulated. |
format | Text |
id | pubmed-2887846 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-28878462010-06-22 Direct Regulation of Striated Muscle Myosins by Nitric Oxide and Endogenous Nitrosothiols Evangelista, Alicia M. Rao, Vijay S. Filo, Ashley R. Marozkina, Nadzeya V. Doctor, Allan Jones, David R. Gaston, Benjamin Guilford, William H. PLoS One Research Article BACKGROUND: Nitric oxide (NO) has long been recognized to affect muscle contraction [1], both through activation of guanylyl cyclase and through modification of cysteines in proteins to yield S-nitrosothiols. While NO affects the contractile apparatus directly, the identities of the target myofibrillar proteins remain unknown. Here we report that nitrogen oxides directly regulate striated muscle myosins. PRINCIPAL FINDINGS: Exposure of skeletal and cardiac myosins to physiological concentrations of nitrogen oxides, including the endogenous nitrosothiol S-nitroso-L-cysteine, reduced the velocity of actin filaments over myosin in a dose-dependent and oxygen-dependent manner, caused a doubling of force as measured in a laser trap transducer, and caused S-nitrosylation of cysteines in the myosin heavy chain. These biomechanical effects were not observed in response to S-nitroso-D-cysteine, demonstrating specificity for the naturally occurring isomer. Both myosin heavy chain isoforms in rats and cardiac myosin heavy chain from human were S-nitrosylated in vivo. SIGNIFICANCE: These data show that nitrosylation signaling acts as a molecular “gear shift” for myosin—an altogether novel mechanism by which striated muscle and cellular biomechanics may be regulated. Public Library of Science 2010-06-18 /pmc/articles/PMC2887846/ /pubmed/20585450 http://dx.doi.org/10.1371/journal.pone.0011209 Text en Evangelista 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 Evangelista, Alicia M. Rao, Vijay S. Filo, Ashley R. Marozkina, Nadzeya V. Doctor, Allan Jones, David R. Gaston, Benjamin Guilford, William H. Direct Regulation of Striated Muscle Myosins by Nitric Oxide and Endogenous Nitrosothiols |
title | Direct Regulation of Striated Muscle Myosins by Nitric Oxide and Endogenous Nitrosothiols |
title_full | Direct Regulation of Striated Muscle Myosins by Nitric Oxide and Endogenous Nitrosothiols |
title_fullStr | Direct Regulation of Striated Muscle Myosins by Nitric Oxide and Endogenous Nitrosothiols |
title_full_unstemmed | Direct Regulation of Striated Muscle Myosins by Nitric Oxide and Endogenous Nitrosothiols |
title_short | Direct Regulation of Striated Muscle Myosins by Nitric Oxide and Endogenous Nitrosothiols |
title_sort | direct regulation of striated muscle myosins by nitric oxide and endogenous nitrosothiols |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2887846/ https://www.ncbi.nlm.nih.gov/pubmed/20585450 http://dx.doi.org/10.1371/journal.pone.0011209 |
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