Differential Autophagy Response in Men and Women After Muscle Damage

Following muscle damage, autophagy is crucial for muscle regeneration. Hormones (e.g., testosterone, cortisol) regulate this process and sex differences in autophagic flux exist in the basal state. However, to date, no study has examined the effect of a transient hormonal response following eccentri...

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Autores principales:	Hui-Ying Luk, Casey Appell, Danielle E. Levitt, Nigel C. Jiwan, Jakob L. Vingren
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	cortisol growth hormone LC3-II/LC3-I ratio macroautophagy sex dimorphism Physiology QP1-981
Acceso en línea:	https://doaj.org/article/6e4b1f16cacb4345a4182f2b8a792fe9
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spelling	oai:doaj.org-article:6e4b1f16cacb4345a4182f2b8a792fe92021-11-30T18:06:10ZDifferential Autophagy Response in Men and Women After Muscle Damage1664-042X10.3389/fphys.2021.752347https://doaj.org/article/6e4b1f16cacb4345a4182f2b8a792fe92021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphys.2021.752347/fullhttps://doaj.org/toc/1664-042XFollowing muscle damage, autophagy is crucial for muscle regeneration. Hormones (e.g., testosterone, cortisol) regulate this process and sex differences in autophagic flux exist in the basal state. However, to date, no study has examined the effect of a transient hormonal response following eccentric exercise-induced muscle damage (EE) between untrained young men and women. Untrained men (n = 8, 22 ± 3 years) and women (n = 8, 19 ± 1 year) completed two sessions of 80 unilateral maximal eccentric knee extensions followed by either upper body resistance exercise (RE; designed to induce a hormonal response; EE + RE) or a time-matched rest period (20 min; EE + REST). Vastus lateralis biopsy samples were collected before (BL), and 12 h, and 24 h after RE/REST. Gene and protein expression levels of selective markers for autophagic initiation signaling, phagophore initiation, and elongation/sequestration were determined. Basal markers of autophagy were not different between sexes. For EE + RE, although initiation signaling (FOXO3) and autophagy-promoting (BECN1) genes were greater (p < 0.0001; 12.4-fold, p = 0.0010; 10.5-fold, respectively) for women than men, autophagic flux (LC3-II/LC3-I protein ratio) did not change for women and was lower (p < 0.0001 3.0-fold) than men. Furthermore, regardless of hormonal changes, LC3-I and LC3-II protein content decreased (p = 0.0090; 0.547-fold, p = 0.0410; 0.307-fold, respectively) for men suggesting increased LC3-I lipidation and autophagosome degradation whereas LC3-I protein content increased (p = 0.0360; 1.485-fold) for women suggesting decreased LC3-I lipidation. Collectively, our findings demonstrated basal autophagy was not different between men and women, did not change after EE alone, and was promoted with the acute hormonal increase after RE only in men but not in women. Thus, the autophagy response to moderate muscle damage is promoted by RE-induced hormonal changes in men only.Hui-Ying LukCasey AppellDanielle E. LevittDanielle E. LevittNigel C. JiwanJakob L. VingrenFrontiers Media S.A.articlecortisolgrowth hormoneLC3-II/LC3-I ratiomacroautophagysex dimorphismPhysiologyQP1-981ENFrontiers in Physiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cortisol growth hormone LC3-II/LC3-I ratio macroautophagy sex dimorphism Physiology QP1-981
spellingShingle	cortisol growth hormone LC3-II/LC3-I ratio macroautophagy sex dimorphism Physiology QP1-981 Hui-Ying Luk Casey Appell Danielle E. Levitt Danielle E. Levitt Nigel C. Jiwan Jakob L. Vingren Differential Autophagy Response in Men and Women After Muscle Damage
description	Following muscle damage, autophagy is crucial for muscle regeneration. Hormones (e.g., testosterone, cortisol) regulate this process and sex differences in autophagic flux exist in the basal state. However, to date, no study has examined the effect of a transient hormonal response following eccentric exercise-induced muscle damage (EE) between untrained young men and women. Untrained men (n = 8, 22 ± 3 years) and women (n = 8, 19 ± 1 year) completed two sessions of 80 unilateral maximal eccentric knee extensions followed by either upper body resistance exercise (RE; designed to induce a hormonal response; EE + RE) or a time-matched rest period (20 min; EE + REST). Vastus lateralis biopsy samples were collected before (BL), and 12 h, and 24 h after RE/REST. Gene and protein expression levels of selective markers for autophagic initiation signaling, phagophore initiation, and elongation/sequestration were determined. Basal markers of autophagy were not different between sexes. For EE + RE, although initiation signaling (FOXO3) and autophagy-promoting (BECN1) genes were greater (p < 0.0001; 12.4-fold, p = 0.0010; 10.5-fold, respectively) for women than men, autophagic flux (LC3-II/LC3-I protein ratio) did not change for women and was lower (p < 0.0001 3.0-fold) than men. Furthermore, regardless of hormonal changes, LC3-I and LC3-II protein content decreased (p = 0.0090; 0.547-fold, p = 0.0410; 0.307-fold, respectively) for men suggesting increased LC3-I lipidation and autophagosome degradation whereas LC3-I protein content increased (p = 0.0360; 1.485-fold) for women suggesting decreased LC3-I lipidation. Collectively, our findings demonstrated basal autophagy was not different between men and women, did not change after EE alone, and was promoted with the acute hormonal increase after RE only in men but not in women. Thus, the autophagy response to moderate muscle damage is promoted by RE-induced hormonal changes in men only.
format	article
author	Hui-Ying Luk Casey Appell Danielle E. Levitt Danielle E. Levitt Nigel C. Jiwan Jakob L. Vingren
author_facet	Hui-Ying Luk Casey Appell Danielle E. Levitt Danielle E. Levitt Nigel C. Jiwan Jakob L. Vingren
author_sort	Hui-Ying Luk
title	Differential Autophagy Response in Men and Women After Muscle Damage
title_short	Differential Autophagy Response in Men and Women After Muscle Damage
title_full	Differential Autophagy Response in Men and Women After Muscle Damage
title_fullStr	Differential Autophagy Response in Men and Women After Muscle Damage
title_full_unstemmed	Differential Autophagy Response in Men and Women After Muscle Damage
title_sort	differential autophagy response in men and women after muscle damage
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6e4b1f16cacb4345a4182f2b8a792fe9
work_keys_str_mv	AT huiyingluk differentialautophagyresponseinmenandwomenaftermuscledamage AT caseyappell differentialautophagyresponseinmenandwomenaftermuscledamage AT danielleelevitt differentialautophagyresponseinmenandwomenaftermuscledamage AT danielleelevitt differentialautophagyresponseinmenandwomenaftermuscledamage AT nigelcjiwan differentialautophagyresponseinmenandwomenaftermuscledamage AT jakoblvingren differentialautophagyresponseinmenandwomenaftermuscledamage
_version_	1718406385558880256

Differential Autophagy Response in Men and Women After Muscle Damage

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