Characterizing SERCA Function in Murine Skeletal Muscles after 35–37 Days of Spaceflight

It is well established that microgravity exposure causes significant muscle weakness and atrophy via muscle unloading. On Earth, muscle unloading leads to a disproportionate loss in muscle force and size with the loss in muscle force occurring at a faster rate. Although the exact mechanisms are unkn...

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Autores principales:	Jessica L. Braun, Mia S. Geromella, Sophie I. Hamstra, Holt N. Messner, Val A. Fajardo
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	spaceflight calcium handling phospholamban sarcolipin neuronatin muscle fiber type Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/e931aabb67a54567a32d8480e83d7e42
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spelling	oai:doaj.org-article:e931aabb67a54567a32d8480e83d7e422021-11-11T17:12:57ZCharacterizing SERCA Function in Murine Skeletal Muscles after 35–37 Days of Spaceflight10.3390/ijms2221117641422-00671661-6596https://doaj.org/article/e931aabb67a54567a32d8480e83d7e422021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11764https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067It is well established that microgravity exposure causes significant muscle weakness and atrophy via muscle unloading. On Earth, muscle unloading leads to a disproportionate loss in muscle force and size with the loss in muscle force occurring at a faster rate. Although the exact mechanisms are unknown, a role for Ca<sup>2+</sup> dysregulation has been suggested. The sarco(endo)plasmic reticulum Ca<sup>2+</sup> ATPase (SERCA) pump actively brings cytosolic Ca<sup>2+</sup> into the SR, eliciting muscle relaxation and maintaining low intracellular Ca<sup>2+</sup> ([Ca<sup>2+</sup>]<sub>i</sub>). SERCA dysfunction contributes to elevations in [Ca<sup>2+</sup>]<sub>i</sub>, leading to cellular damage, and may contribute to the muscle weakness and atrophy observed with spaceflight. Here, we investigated SERCA function, SERCA regulatory protein content, and reactive oxygen/nitrogen species (RONS) protein adduction in murine skeletal muscle after 35–37 days of spaceflight. In male and female soleus muscles, spaceflight led to drastic impairments in Ca<sup>2+</sup> uptake despite significant increases in SERCA1a protein content. We attribute this impairment to an increase in RONS production and elevated total protein tyrosine (T) nitration and cysteine (S) nitrosylation. Contrarily, in the tibialis anterior (TA), we observed an enhancement in Ca<sup>2+</sup> uptake, which we attribute to a shift towards a faster muscle fiber type (i.e., increased myosin heavy chain IIb and SERCA1a) without elevated total protein T-nitration and S-nitrosylation. Thus, spaceflight affects SERCA function differently between the soleus and TA.Jessica L. BraunMia S. GeromellaSophie I. HamstraHolt N. MessnerVal A. FajardoMDPI AGarticlespaceflightcalcium handlingphospholambansarcolipinneuronatinmuscle fiber typeBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11764, p 11764 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	spaceflight calcium handling phospholamban sarcolipin neuronatin muscle fiber type Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	spaceflight calcium handling phospholamban sarcolipin neuronatin muscle fiber type Biology (General) QH301-705.5 Chemistry QD1-999 Jessica L. Braun Mia S. Geromella Sophie I. Hamstra Holt N. Messner Val A. Fajardo Characterizing SERCA Function in Murine Skeletal Muscles after 35–37 Days of Spaceflight
description	It is well established that microgravity exposure causes significant muscle weakness and atrophy via muscle unloading. On Earth, muscle unloading leads to a disproportionate loss in muscle force and size with the loss in muscle force occurring at a faster rate. Although the exact mechanisms are unknown, a role for Ca<sup>2+</sup> dysregulation has been suggested. The sarco(endo)plasmic reticulum Ca<sup>2+</sup> ATPase (SERCA) pump actively brings cytosolic Ca<sup>2+</sup> into the SR, eliciting muscle relaxation and maintaining low intracellular Ca<sup>2+</sup> ([Ca<sup>2+</sup>]<sub>i</sub>). SERCA dysfunction contributes to elevations in [Ca<sup>2+</sup>]<sub>i</sub>, leading to cellular damage, and may contribute to the muscle weakness and atrophy observed with spaceflight. Here, we investigated SERCA function, SERCA regulatory protein content, and reactive oxygen/nitrogen species (RONS) protein adduction in murine skeletal muscle after 35–37 days of spaceflight. In male and female soleus muscles, spaceflight led to drastic impairments in Ca<sup>2+</sup> uptake despite significant increases in SERCA1a protein content. We attribute this impairment to an increase in RONS production and elevated total protein tyrosine (T) nitration and cysteine (S) nitrosylation. Contrarily, in the tibialis anterior (TA), we observed an enhancement in Ca<sup>2+</sup> uptake, which we attribute to a shift towards a faster muscle fiber type (i.e., increased myosin heavy chain IIb and SERCA1a) without elevated total protein T-nitration and S-nitrosylation. Thus, spaceflight affects SERCA function differently between the soleus and TA.
format	article
author	Jessica L. Braun Mia S. Geromella Sophie I. Hamstra Holt N. Messner Val A. Fajardo
author_facet	Jessica L. Braun Mia S. Geromella Sophie I. Hamstra Holt N. Messner Val A. Fajardo
author_sort	Jessica L. Braun
title	Characterizing SERCA Function in Murine Skeletal Muscles after 35–37 Days of Spaceflight
title_short	Characterizing SERCA Function in Murine Skeletal Muscles after 35–37 Days of Spaceflight
title_full	Characterizing SERCA Function in Murine Skeletal Muscles after 35–37 Days of Spaceflight
title_fullStr	Characterizing SERCA Function in Murine Skeletal Muscles after 35–37 Days of Spaceflight
title_full_unstemmed	Characterizing SERCA Function in Murine Skeletal Muscles after 35–37 Days of Spaceflight
title_sort	characterizing serca function in murine skeletal muscles after 35–37 days of spaceflight
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e931aabb67a54567a32d8480e83d7e42
work_keys_str_mv	AT jessicalbraun characterizingsercafunctioninmurineskeletalmusclesafter3537daysofspaceflight AT miasgeromella characterizingsercafunctioninmurineskeletalmusclesafter3537daysofspaceflight AT sophieihamstra characterizingsercafunctioninmurineskeletalmusclesafter3537daysofspaceflight AT holtnmessner characterizingsercafunctioninmurineskeletalmusclesafter3537daysofspaceflight AT valafajardo characterizingsercafunctioninmurineskeletalmusclesafter3537daysofspaceflight
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Characterizing SERCA Function in Murine Skeletal Muscles after 35–37 Days of Spaceflight

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