Involvment of c-Abl in the radiation-induced inhibition of myoblast differentiation.
OBJECTIVE
While radiation-induced differentiation is common in many cell types it has been shown (Ikeda et al. 2000) that irradiation inhibits differentiation of murine myoblast cell line C2C12. To investigate the mechanisms responsible for this phenomenon we looked into the role of the non-receptor tyrosine kinase c-Abl.


METHODS
C-Abl activity was determined using an immune-complex kinase assay and the functional role of c-Abl activity was assessed by using the kinase inhibitor STI 571 (Gleevec) and by transfecting a dominant negative c-Abl mutant (K290R).


RESULTS
We found an up-regulation of c-Abl activity 6h after differentiation induction when compared to uninduced control cells. Exposure of C2C12 cells to ionizing radiation, which inhibits myotube formation, inhibited this up-regulation. Transfected dominant negative c-Abl as well as STI 571 treatment and ionizing radiation inhibited myotube formation but did not significantly suppress the expression of the muscle-specific transcription factor Myogenin or of the differentiation marker Myosin heavy chain.


CONCLUSIONS
These data suggest that c-Abl is involved in the radiation-induced inhibition of myoblast differentiation and lead to the hypothesis that c-Abl plays a role in late events during myogenic differentiation probably in the process of myoblast fusion.
Hoerth
E
E
Department of Radiobiology, Clinic for Radiotherapy and Radiobiology, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Kodym
R
R
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology / Q000528:radiation effects*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression; D051379:Mice; D009154:Mutation; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000502:physiology*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation
D004791:Enzyme Inhibitors; C503801:Myog protein, mouse; D018008:Myogenin; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl; D018995:Myosin Heavy Chains