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

Dibenedetto, S; Niklison-Chirou, M; Cabrera, CP; Ellis, M; Robson, LG; Knopp, P; Tedesco, FS; ... Marino, S; + view all (2017) Enhanced Energetic State and Protection from Oxidative Stress in Human Myoblasts Overexpressing BMI1. Stem Cell Reports , 9 (2) pp. 528-542. 10.1016/j.stemcr.2017.06.009. Green open access

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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.

Type: Article
Title: Enhanced Energetic State and Protection from Oxidative Stress in Human Myoblasts Overexpressing BMI1
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.stemcr.2017.06.009
Publisher version: http://doi.org/10.1016/j.stemcr.2017.06.009
Language: English
Additional information: Copyright © 2017 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: DMD, Polycomb gene, muscle regeneration, myoblasts, myopathy, oxidative phosphorylation, satellite cells
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1567652
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