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Long-term PGC1? overexpression leads to apoptosis, autophagy and muscle wasting.

ABSTRACT: Skeletal muscle wasting is prevalent in many chronic diseases, necessitating inquiries into molecular regulation of muscle mass. Nuclear receptor co-activator peroxisome proliferator-activated receptor co-activator 1 alpha (PGC1?) and its splice variant PGC1?4 increase skeletal muscle mass. However, the effect of the other PGC1 sub-type, PGC1?, on muscle size is unclear. In transgenic mice selectively over-expressing PGC1? in the skeletal muscle, we have found that PGC1? progressively decreases skeletal muscle mass predominantly associated with loss of type 2b fast-twitch myofibers. Paradoxically, PGC1? represses the ubiquitin-proteolysis degradation pathway genes resulting in ubiquitinated protein accumulation in muscle. However, PGC1? overexpression triggers up-regulation of apoptosis and autophagy genes, resulting in robust activation of these cell degenerative processes, and a concomitant increase in muscle protein oxidation. Concurrently, PGC1? up-regulates apoptosis and/or autophagy transcriptional factors such as E2f1, Atf3, Stat1, and Stat3, which may be facilitating myopathy. Therefore, PGC1? activation negatively affects muscle mass over time, particularly fast-twitch muscles, which should be taken into consideration along with its known aerobic effects in the skeletal muscle.

SUBMITTER: Sopariwala DH

PROVIDER: S-EPMC5578977 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Long-term PGC1β overexpression leads to apoptosis, autophagy and muscle wasting.

Sopariwala Danesh H DH Yadav Vikas V Badin Pierre-Marie PM Likhite Neah N Sheth Megha M Lorca Sabina S Vila Isabelle K IK Kim Eun Ran ER Tong Qingchun Q Song Min Sup MS Rodney George G GG Narkar Vihang A VA

Scientific reports 20170831 1

Skeletal muscle wasting is prevalent in many chronic diseases, necessitating inquiries into molecular regulation of muscle mass. Nuclear receptor co-activator peroxisome proliferator-activated receptor co-activator 1 alpha (PGC1α) and its splice variant PGC1α4 increase skeletal muscle mass. However, the effect of the other PGC1 sub-type, PGC1β, on muscle size is unclear. In transgenic mice selectively over-expressing PGC1β in the skeletal muscle, we have found that PGC1β progressively decreases ...[more]

PMID: 28860475

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Long-term PGC1? overexpression leads to apoptosis, autophagy and muscle wasting.

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Long-term PGC1β overexpression leads to apoptosis, autophagy and muscle wasting.

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