1. Down-regulation of pro-necroptotic molecules blunts necroptosis during myogenesis
- Author
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Ju-Hui Kang, Kwang-Ho Lee, Se-Bin Lee, Tae-Yeon Kim, and Tae-Bong Kang
- Subjects
Male ,0301 basic medicine ,Programmed cell death ,Necroptosis ,Biophysics ,Down-Regulation ,Apoptosis ,Biology ,Muscle Development ,Biochemistry ,Mice ,03 medical and health sciences ,RIPK1 ,0302 clinical medicine ,medicine ,Animals ,Myocyte ,Phosphorylation ,Muscle, Skeletal ,Molecular Biology ,Cells, Cultured ,Myogenesis ,Skeletal muscle ,Cell Differentiation ,Cell Biology ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Receptor-Interacting Protein Serine-Threonine Kinases ,030220 oncology & carcinogenesis ,Signal transduction ,Protein Kinases ,C2C12 ,Signal Transduction - 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.
- Published
- 2021