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Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
Apoptosis repressor with caspase recruitment domain (ARC) inhibits myogenic differentiation
Arwen L Hunter1, Jingchun Zhang, Shirley C Chen
1James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Department of Pathology and Laboratory Medicine, St. Paul's Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, BC, Canada.
Abstract:
Apoptosis repressor with caspase recruitment domain (ARC), an anti-apoptotic protein, is highly expressed in differentiated heart and skeletal muscle. Apoptosis and differentiation share numerous common pathways; therefore, we examined the impact of ARC on H9c2-myoblast differentiation. We demonstrate that ARC expression levels increase and stabilize upon differentiation. ARC-overexpression in pre-differentiated H9c2-cells suppresses differentiation; indicated by increased myotube formation, nuclear fusion and expression of the differentiation markers myogenin and troponin-T. ARC-overexpression inhibited myoblast differentiation associated caspase-3 activation, suggesting ARC inhibits myogenic differentiation through caspase inhibition. In summary, we show a novel role for ARC in the regulation of muscle differentiation.
Insights
Apoptosis repressor with caspase recruitment domain (ARC) suppresses muscle cell differentiation by inhibiting caspase activation. This study reveals ARC
Area of Science:
- Muscle cell biology
- Apoptosis regulation
- Cellular differentiation pathways
Background:
- Apoptosis repressor with caspase recruitment domain (ARC) is an anti-apoptotic protein.
- ARC is highly expressed in differentiated cardiac and skeletal muscle tissues.
- Muscle differentiation and apoptosis share common regulatory pathways.
Purpose of the Study:
- To investigate the role of ARC in H9c2-myoblast differentiation.
- To determine if ARC influences key markers and processes of myogenic differentiation.
Main Methods:
- Overexpression of ARC in H9c2-myoblasts.
- Assessment of differentiation markers (myotube formation, nuclear fusion, myogenin, troponin-T).
- Analysis of caspase-3 activation during differentiation.
Main Results:
- ARC expression increases and stabilizes during H9c2-myoblast differentiation.
- ARC overexpression suppressed differentiation, evidenced by enhanced myotube formation and nuclear fusion.
- ARC overexpression inhibited caspase-3 activation, a key event in myogenic differentiation.
Conclusions:
- ARC plays a novel inhibitory role in muscle differentiation.
- ARC may regulate myogenic differentiation through the inhibition of caspase activity.
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