Accessibility of myofilament cysteines and effects on ATPase depend on the activation state during exposure to oxidants.

Signaling by reactive oxygen species has emerged as a major physiological process. Due to its high metabolic rate, striated muscle is especially subject to oxidative stress, and there are multiple examples in cardiac and skeletal muscle where oxidative stress modulates contractile function. Here we...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sean M Gross, Steven L Lehman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/56b921ad6f054747a2c9b04eb0454962
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:56b921ad6f054747a2c9b04eb0454962
record_format	dspace
spelling	oai:doaj.org-article:56b921ad6f054747a2c9b04eb04549622021-11-18T09:03:48ZAccessibility of myofilament cysteines and effects on ATPase depend on the activation state during exposure to oxidants.1932-620310.1371/journal.pone.0069110https://doaj.org/article/56b921ad6f054747a2c9b04eb04549622013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23894416/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Signaling by reactive oxygen species has emerged as a major physiological process. Due to its high metabolic rate, striated muscle is especially subject to oxidative stress, and there are multiple examples in cardiac and skeletal muscle where oxidative stress modulates contractile function. Here we assessed the potential of cysteine oxidation as a mechanism for modulating contractile function in skeletal and cardiac muscle. Analyzing the cysteine content of the myofilament proteins in striated muscle, we found that cysteine residues are relatively rare, but are very similar between different muscle types and different vertebrate species. To refine this list of cysteines to those that may modulate function, we estimated the accessibility of oxidants to cysteine residues using protein crystal structures, and then sharpened these estimates using fluorescent labeling of cysteines in cardiac and skeletal myofibrils. We demonstrate that cysteine accessibility to oxidants and ATPase rates depend on the contractile state in which preparations are exposed. Oxidant exposure of skeletal and cardiac myofibrils in relaxing solution exposes myosin cysteines not accessible in rigor solution, and these modifications correspond to a decrease in maximum ATPase. Oxidant exposure under rigor conditions produces modifications that increase basal ATPase and calcium sensitivity in ventricular myofibrils, but these effects were muted in fast twitch muscle. These experiments reveal how structural and sequence variations can lead to divergent effects from oxidants in different muscle types.Sean M GrossSteven L LehmanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e69110 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sean M Gross Steven L Lehman Accessibility of myofilament cysteines and effects on ATPase depend on the activation state during exposure to oxidants.
description	Signaling by reactive oxygen species has emerged as a major physiological process. Due to its high metabolic rate, striated muscle is especially subject to oxidative stress, and there are multiple examples in cardiac and skeletal muscle where oxidative stress modulates contractile function. Here we assessed the potential of cysteine oxidation as a mechanism for modulating contractile function in skeletal and cardiac muscle. Analyzing the cysteine content of the myofilament proteins in striated muscle, we found that cysteine residues are relatively rare, but are very similar between different muscle types and different vertebrate species. To refine this list of cysteines to those that may modulate function, we estimated the accessibility of oxidants to cysteine residues using protein crystal structures, and then sharpened these estimates using fluorescent labeling of cysteines in cardiac and skeletal myofibrils. We demonstrate that cysteine accessibility to oxidants and ATPase rates depend on the contractile state in which preparations are exposed. Oxidant exposure of skeletal and cardiac myofibrils in relaxing solution exposes myosin cysteines not accessible in rigor solution, and these modifications correspond to a decrease in maximum ATPase. Oxidant exposure under rigor conditions produces modifications that increase basal ATPase and calcium sensitivity in ventricular myofibrils, but these effects were muted in fast twitch muscle. These experiments reveal how structural and sequence variations can lead to divergent effects from oxidants in different muscle types.
format	article
author	Sean M Gross Steven L Lehman
author_facet	Sean M Gross Steven L Lehman
author_sort	Sean M Gross
title	Accessibility of myofilament cysteines and effects on ATPase depend on the activation state during exposure to oxidants.
title_short	Accessibility of myofilament cysteines and effects on ATPase depend on the activation state during exposure to oxidants.
title_full	Accessibility of myofilament cysteines and effects on ATPase depend on the activation state during exposure to oxidants.
title_fullStr	Accessibility of myofilament cysteines and effects on ATPase depend on the activation state during exposure to oxidants.
title_full_unstemmed	Accessibility of myofilament cysteines and effects on ATPase depend on the activation state during exposure to oxidants.
title_sort	accessibility of myofilament cysteines and effects on atpase depend on the activation state during exposure to oxidants.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/56b921ad6f054747a2c9b04eb0454962
work_keys_str_mv	AT seanmgross accessibilityofmyofilamentcysteinesandeffectsonatpasedependontheactivationstateduringexposuretooxidants AT stevenllehman accessibilityofmyofilamentcysteinesandeffectsonatpasedependontheactivationstateduringexposuretooxidants
_version_	1718420964890378240

Accessibility of myofilament cysteines and effects on ATPase depend on the activation state during exposure to oxidants.

Ejemplares similares