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Down-regulation of pro-necroptotic molecules blunts necroptosis during myogenesis. | LitMetric

Down-regulation of pro-necroptotic molecules blunts necroptosis during myogenesis.

Biochem Biophys Res Commun

Department of Applied Life Sciences, Graduate School, BK21 Program, Konkuk University, Chungju, 27478, Republic of Korea; Department of Biotechnology, College of Biomedical & Health Science, Konkuk University, Chungju, 27487, Republic of Korea.

Published: June 2021

AI Article Synopsis

  • Cell death and muscle cell differentiation are interconnected, with differentiation reducing the likelihood of apoptosis in skeletal muscle cells.
  • The study focused on how undifferentiated myoblasts and differentiated myotubes respond to necroptosis induced by TNF, finding that differentiation reduces this sensitivity.
  • Key molecules (RIPK1, RIPK3, MLKL) involved in necroptosis were shown to decrease significantly during muscle differentiation, indicating that mature muscle tissue is less prone to this form of cell death compared to immature muscle.

Article Abstract

Cell death and differentiation are closely related at the molecular level. Differentiation of skeletal muscle cells attenuates susceptibility to apoptosis. Necroptosis has recently been recognized as a form of regulated cell death but its role in myogenesis has not been studied. This study aimed to compare the sensitivity to TNF-induced necroptosis in skeletal muscle at the undifferentiated (myoblasts) and differentiated (myotubes) stages. Surprisingly, our results showed that TNF-induced necroptosis was blunted during myoblast differentiation. Moreover, our data revealed that the key molecules involved in necroptosis, including receptor-interacting serine/threonine protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL), were significantly down-regulated during myogenic differentiation, resulting in suppression of necroptosis signal transduction in differentiated myotubes. In addition, RIPK1, RIPK3, and MLKL expression levels were significantly lower in the skeletal muscle of adult mice than in newborn mice, suggesting that the susceptibility to necroptosis might be attenuated in differentiated muscle tissue. In conclusion, this study revealed that expression of key molecules involved in necroptosis is down-regulated during muscle differentiation, which results in the differentiation of muscles becoming insensitive to necroptotic cell death.

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Source
http://dx.doi.org/10.1016/j.bbrc.2021.04.004DOI Listing

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