Survival-apoptosis associated signaling in GNE myopathy-cultured myoblasts

Avi Harazi, Malka Chaouat, Zippora Shlomai, Robina Levitzki, Michal Becker-Cohen, Menachem Sadeh, Ron Dabby, Hannah Ben-Bassat, Stella Mitrani-Rosenbaum

Research output: Contribution to journalArticlepeer-review


GNE Myopathy (GNEM) is a neuromuscular disorder caused by mutations in the GNE gene. It is a slowly progressive distal and proximal muscle weakness sparing the quadriceps. In this study, we applied our model of mutated M743T GNE enzyme skeletal muscle-cultured myoblasts and paired healthy controls to depict the pattern of signaling proteins controlling survival and/or apoptosis of the PI3K/AKT, BCL2, ARTS/XIAP pathways, examined the effects of metabolic changes/stimuli on their expression and activation, and their potential role in GNEM. Immunoblot analysis of the GNEM myoblasts indicated a notable increased level of activated PTEN and PDK1 and a trend of relative differences in the expression and activation of the examined signaling molecules with variability among the cultures. ANOVA analysis showed a highly significant interaction between the level of PTEN and the patients groups. In parallel, the interaction between the level of BCL2, BAX and PTEN with the specific PI3K/AKT inhibitor-LY294002 was highly significant for BCL2 and nearly significant for PTEN and BAX. The pattern of the ARTS/XIAP signaling proteins of GNEM and the paired controls was variable, with no significant differences between the two cell types. The response of the GNEM cells to the metabolic changes/stimuli: serum depletion and insulin challenge, as indicated by expression of selected signaling proteins, was variable and similar to the control cells. Taken together, our observations provide a clearer insight into specific signaling molecules influencing growth and survival of GNEM muscle cells.

Original languageEnglish
Pages (from-to)249-257
Number of pages9
JournalJournal of Receptor and Signal Transduction Research
Issue number4
StatePublished - 4 Jul 2015
Externally publishedYes


  • BCL2
  • GNE
  • GNE myopathy (GNEM)
  • PI3K/AKT
  • Signaling
  • Skeletal muscle myoblasts


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