ArticlePloS one2009
Skeletal muscle differentiation evokes endogenous XIAP to restrict the apoptotic pathway.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 42 citations in OpenAlex.
- Early Taurine Administration Decreases the Levels of Receptor-Interacting Serine/Threonine Protein Kinase 1 in the Duchenne Mouse ModelBrain sciences · 2025Article
- Article
- Targeting necroptosis in muscle fibers ameliorates inflammatory myopathies.Nature communications · 2022Article
- Non-Canonical Roles of Apoptotic Caspases in the Nervous System.Frontiers in cell and developmental biology · 2022Review
- Apoptotic cell death regulation in neurons.The FEBS journal · 2019Review
- Pharmacological targeting of HSP90 with 17-AAG induces apoptosis of myogenic cells through activation of the intrinsic pathway.Molecular and cellular biochemistry · 2018Article
- Skeletal Muscles Do Not Undergo Apoptosis During Either Atrophy or Programmed Cell Death-Revisiting the Myonuclear Domain Hypothesis.Frontiers in physiology · 2018Review
- Mature neurons dynamically restrict apoptosis via redundant premitochondrial brakes.The FEBS journal · 2016Article
- Stem cell death and survival in heart regeneration and repair.Apoptosis : an international journal on programmed cell death · 2016Review
- An Analysis of the Truncated Bid- and ROS-dependent Spatial Propagation of Mitochondrial Permeabilization Waves during Apoptosis.The Journal of biological chemistry · 2016Article
- The beneficial role of proteolysis in skeletal muscle growth and stress adaptation.Skeletal muscle · 2016Review
- The E3 ligase PARC mediates the degradation of cytosolic cytochrome c to promote survival in neurons and cancer cells.Science signaling · 2014Article
- DNA damage response by single-strand breaks in terminally differentiated muscle cells and the control of muscle integrity.Cell death and differentiation · 2012Article
- β-Hydroxy-β-methylbutyrate reduces myonuclear apoptosis during recovery from hind limb suspension-induced muscle fiber atrophy in aged rats.American journal of physiology. Regulatory, integrative and comparative physiology · 2011Article
- Cell death-resistance of differentiated myotubes is associated with enhanced anti-apoptotic mechanisms compared to myoblasts.Apoptosis : an international journal on programmed cell death · 2011Article
- MyoD regulates apoptosis of myoblasts through microRNA-mediated down-regulation of Pax3.The Journal of cell biology · 2010Article
- XIAP impairs Smac release from the mitochondria during apoptosis.Cell death & disease · 2010Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Myotube apoptosis occurs normally during muscle development and aging but it can lead to destruction of skeletal muscle in neuromuscular diseases. Therefore, understanding how myotube apoptosis is regulated is important for developing novel strategies for treatment of muscle loss. We investigated the regulation of apoptosis in skeletal muscle and report a striking increase in resistance to apoptosis following differentiation. We find mitotic C2C12 cells (myoblast-like cells) are sensitive to cytosolic cytochrome c microinjection. However, differentiated C2C12 cells (myotube-like cells) and primary myotubes are markedly resistant. This resistance is due to endogenous X-linked inhibitor of apoptotic protein (XIAP). Importantly, the selective difference in the ability of XIAP to block myotube but not myoblast apoptosis is not due to a change in XIAP but rather a decrease in Apaf-1 expression. This decrease in Apaf-1 links XIAP to caspase activation and death. Our findings suggest that in order for myotubes to die, they may degrade XIAP, functionally inactivate XIAP or upregulate Apaf-1. Importantly, we identify a role for endogenous Smac in overcoming XIAP to allow myotube death. However, in postmitotic cardiomyocytes, where XIAP also restricts apoptosis, endogenous Smac was not capable of overcoming XIAP to cause death. These results show that as skeletal muscle differentiate, they become resistant to apoptosis because of the ability of XIAP to regulate caspase activation. The increased restriction of apoptosis in myotubes is presumably important to ensure the long term survival of these postmitotic cells as they play a vital role in the physiology of organisms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.