Enhanced Energetic State and Protection from Oxidative Stress in Human Myoblasts Overexpressing BMI1

Silvia Dibenedetto; Maria Niklison-Chirou; Claudia P. Cabrera; Matthew Ellis; Lesley G. Robson; Paul Knopp; Francesco Saverio Tedesco; Martina Ragazzi; Valentina Di Foggia; Michael R. Barnes; Aleksandar Radunovic; Silvia Marino

doi:10.1016/j.stemcr.2017.06.009

Enhanced Energetic State and Protection from Oxidative Stress in Human Myoblasts Overexpressing BMI1

Silvia Dibenedetto, Maria Niklison-Chirou, Claudia P. Cabrera, Matthew Ellis, Lesley G. Robson, Paul Knopp, Francesco Saverio Tedesco, Martina Ragazzi, Valentina Di Foggia, Michael R. Barnes, Aleksandar Radunovic, Silvia Marino

Research output: Contribution to journal › Article › peer-review

7 Citations (SciVal)

Abstract

The Polycomb group gene BMI1 is essential for efficient muscle regeneration in a mouse model of Duchenne muscular dystrophy, and its enhanced expression in adult skeletal muscle satellite cells ameliorates the muscle strength in this model. Here, we show that the impact of mild BMI1 overexpression observed in mouse models is translatable to human cells. In human myoblasts, BMI1 overexpression increases mitochondrial activity, leading to an enhanced energetic state with increased ATP production and concomitant protection against DNA damage both in vitro and upon xenografting in a severe dystrophic mouse model. These preclinical data in mouse models and human cells provide a strong rationale for the development of pharmacological approaches to target BMI1-mediated mitochondrial regulation and protection from DNA damage to sustain the regenerative potential of the skeletal muscle in conditions of chronic muscle wasting.

Original language	English
Pages (from-to)	528-542
Number of pages	15
Journal	Stem Cell Reports
Volume	9
Issue number	2
DOIs	https://doi.org/10.1016/j.stemcr.2017.06.009
Publication status	Published - 8 Aug 2017

Keywords

DMD
muscle regeneration
myoblasts
myopathy
oxidative phosphorylation
Polycomb gene
satellite cells

ASJC Scopus subject areas

Biochemistry
Genetics
Developmental Biology
Cell Biology

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10.1016/j.stemcr.2017.06.009Licence: CC BY

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title = "Enhanced Energetic State and Protection from Oxidative Stress in Human Myoblasts Overexpressing BMI1",

abstract = "The Polycomb group gene BMI1 is essential for efficient muscle regeneration in a mouse model of Duchenne muscular dystrophy, and its enhanced expression in adult skeletal muscle satellite cells ameliorates the muscle strength in this model. Here, we show that the impact of mild BMI1 overexpression observed in mouse models is translatable to human cells. In human myoblasts, BMI1 overexpression increases mitochondrial activity, leading to an enhanced energetic state with increased ATP production and concomitant protection against DNA damage both in vitro and upon xenografting in a severe dystrophic mouse model. These preclinical data in mouse models and human cells provide a strong rationale for the development of pharmacological approaches to target BMI1-mediated mitochondrial regulation and protection from DNA damage to sustain the regenerative potential of the skeletal muscle in conditions of chronic muscle wasting.",

keywords = "DMD, muscle regeneration, myoblasts, myopathy, oxidative phosphorylation, Polycomb gene, satellite cells",

author = "Silvia Dibenedetto and Maria Niklison-Chirou and Cabrera, {Claudia P.} and Matthew Ellis and Robson, {Lesley G.} and Paul Knopp and Tedesco, {Francesco Saverio} and Martina Ragazzi and {Di Foggia}, Valentina and Barnes, {Michael R.} and Aleksandar Radunovic and Silvia Marino",

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AU - Niklison-Chirou, Maria

AU - Cabrera, Claudia P.

AU - Ellis, Matthew

AU - Robson, Lesley G.

AU - Knopp, Paul

AU - Tedesco, Francesco Saverio

AU - Ragazzi, Martina

AU - Di Foggia, Valentina

AU - Barnes, Michael R.

AU - Radunovic, Aleksandar

AU - Marino, Silvia

PY - 2017/8/8

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AB - The Polycomb group gene BMI1 is essential for efficient muscle regeneration in a mouse model of Duchenne muscular dystrophy, and its enhanced expression in adult skeletal muscle satellite cells ameliorates the muscle strength in this model. Here, we show that the impact of mild BMI1 overexpression observed in mouse models is translatable to human cells. In human myoblasts, BMI1 overexpression increases mitochondrial activity, leading to an enhanced energetic state with increased ATP production and concomitant protection against DNA damage both in vitro and upon xenografting in a severe dystrophic mouse model. These preclinical data in mouse models and human cells provide a strong rationale for the development of pharmacological approaches to target BMI1-mediated mitochondrial regulation and protection from DNA damage to sustain the regenerative potential of the skeletal muscle in conditions of chronic muscle wasting.

KW - DMD

KW - muscle regeneration

KW - myoblasts

KW - myopathy

KW - oxidative phosphorylation

KW - Polycomb gene

KW - satellite cells

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ER -

Enhanced Energetic State and Protection from Oxidative Stress in Human Myoblasts Overexpressing BMI1

Abstract

Keywords

ASJC Scopus subject areas

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