Apoptosis-inducing factor regulates skeletal muscle progenitor cell number and muscle phenotype.

Apoptosis Inducing Factor (AIF) is a highly conserved, ubiquitous flavoprotein localized in the mitochondrial intermembrane space. In vivo, AIF provides protection against neuronal and cardiomyocyte apoptosis induced by oxidative stress. Conversely in vitro, AIF has been demonstrated to have a pro-a...

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Autores principales: Anne-Sophie Armand, Iman Laziz, Dounia Djeghloul, Sylvie Lécolle, Anne T Bertrand, Olivier Biondi, Leon J De Windt, Christophe Chanoine
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Publicado: Public Library of Science (PLoS) 2011
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spelling oai:doaj.org-article:cd65edbb7d954aa8a79f6e7af60092b82021-11-18T07:34:54ZApoptosis-inducing factor regulates skeletal muscle progenitor cell number and muscle phenotype.1932-620310.1371/journal.pone.0027283https://doaj.org/article/cd65edbb7d954aa8a79f6e7af60092b82011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22076146/?tool=EBIhttps://doaj.org/toc/1932-6203Apoptosis Inducing Factor (AIF) is a highly conserved, ubiquitous flavoprotein localized in the mitochondrial intermembrane space. In vivo, AIF provides protection against neuronal and cardiomyocyte apoptosis induced by oxidative stress. Conversely in vitro, AIF has been demonstrated to have a pro-apoptotic role upon induction of the mitochondrial death pathway, once AIF translocates to the nucleus where it facilitates chromatin condensation and large scale DNA fragmentation. Given that the aif hypomorphic harlequin (Hq) mutant mouse model displays severe sarcopenia, we examined skeletal muscle from the aif hypomorphic mice in more detail. Adult AIF-deficient skeletal myofibers display oxidative stress and a severe form of atrophy, associated with a loss of myonuclei and a fast to slow fiber type switch, both in "slow" muscles such as soleus, as well as in "fast" muscles such as extensor digitorum longus, most likely resulting from an increase of MEF2 activity. This fiber type switch was conserved in regenerated soleus and EDL muscles of Hq mice subjected to cardiotoxin injection. In addition, muscle regeneration in soleus and EDL muscles of Hq mice was severely delayed. Freshly cultured myofibers, soleus and EDL muscle sections from Hq mice displayed a decreased satellite cell pool, which could be rescued by pretreating aif hypomorphic mice with the manganese-salen free radical scavenger EUK-8. Satellite cell activation seems to be abnormally long in Hq primary culture compared to controls. However, AIF deficiency did not affect myoblast cell proliferation and differentiation. Thus, AIF protects skeletal muscles against oxidative stress-induced damage probably by protecting satellite cells against oxidative stress and maintaining skeletal muscle stem cell number and activation.Anne-Sophie ArmandIman LazizDounia DjeghloulSylvie LécolleAnne T BertrandOlivier BiondiLeon J De WindtChristophe ChanoinePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e27283 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Anne-Sophie Armand
Iman Laziz
Dounia Djeghloul
Sylvie Lécolle
Anne T Bertrand
Olivier Biondi
Leon J De Windt
Christophe Chanoine
Apoptosis-inducing factor regulates skeletal muscle progenitor cell number and muscle phenotype.
description Apoptosis Inducing Factor (AIF) is a highly conserved, ubiquitous flavoprotein localized in the mitochondrial intermembrane space. In vivo, AIF provides protection against neuronal and cardiomyocyte apoptosis induced by oxidative stress. Conversely in vitro, AIF has been demonstrated to have a pro-apoptotic role upon induction of the mitochondrial death pathway, once AIF translocates to the nucleus where it facilitates chromatin condensation and large scale DNA fragmentation. Given that the aif hypomorphic harlequin (Hq) mutant mouse model displays severe sarcopenia, we examined skeletal muscle from the aif hypomorphic mice in more detail. Adult AIF-deficient skeletal myofibers display oxidative stress and a severe form of atrophy, associated with a loss of myonuclei and a fast to slow fiber type switch, both in "slow" muscles such as soleus, as well as in "fast" muscles such as extensor digitorum longus, most likely resulting from an increase of MEF2 activity. This fiber type switch was conserved in regenerated soleus and EDL muscles of Hq mice subjected to cardiotoxin injection. In addition, muscle regeneration in soleus and EDL muscles of Hq mice was severely delayed. Freshly cultured myofibers, soleus and EDL muscle sections from Hq mice displayed a decreased satellite cell pool, which could be rescued by pretreating aif hypomorphic mice with the manganese-salen free radical scavenger EUK-8. Satellite cell activation seems to be abnormally long in Hq primary culture compared to controls. However, AIF deficiency did not affect myoblast cell proliferation and differentiation. Thus, AIF protects skeletal muscles against oxidative stress-induced damage probably by protecting satellite cells against oxidative stress and maintaining skeletal muscle stem cell number and activation.
format article
author Anne-Sophie Armand
Iman Laziz
Dounia Djeghloul
Sylvie Lécolle
Anne T Bertrand
Olivier Biondi
Leon J De Windt
Christophe Chanoine
author_facet Anne-Sophie Armand
Iman Laziz
Dounia Djeghloul
Sylvie Lécolle
Anne T Bertrand
Olivier Biondi
Leon J De Windt
Christophe Chanoine
author_sort Anne-Sophie Armand
title Apoptosis-inducing factor regulates skeletal muscle progenitor cell number and muscle phenotype.
title_short Apoptosis-inducing factor regulates skeletal muscle progenitor cell number and muscle phenotype.
title_full Apoptosis-inducing factor regulates skeletal muscle progenitor cell number and muscle phenotype.
title_fullStr Apoptosis-inducing factor regulates skeletal muscle progenitor cell number and muscle phenotype.
title_full_unstemmed Apoptosis-inducing factor regulates skeletal muscle progenitor cell number and muscle phenotype.
title_sort apoptosis-inducing factor regulates skeletal muscle progenitor cell number and muscle phenotype.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/cd65edbb7d954aa8a79f6e7af60092b8
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