Activation of the interferon system during myogenesis in vitro.
Differentiation of skeletal muscle involves withdrawal of myoblasts from cell replication, fusion to form multinucleated myotubes, coordinate appearance of a variety of muscle-specific proteins and the disappearance of a set of other proteins responsible for cell growth. The possible activation of the interferon (IFN) system in this process was studied. Thus, the activity of two IFN-induced enzymes known to be part of the system-(2'-5') oligoadenylate synthetase (2-5A synthetase) and double-stranded RNA-activated protein kinase as well as the expression of 2-5A synthetase coding genes were examined during myogenesis. It is demonstrated that the activity of the enzymes is transiently increased in cultured myoblasts, reaching a peak activity on the 3rd day in culture and then declining to a basal level. This peak activity precedes both cell fusion and the appearance of muscle-specific proteins--acetylcholine receptors (AChR) and creatine kinase. The same kinetics of 2-5A synthetase activity was evident in myoblasts from chick, rat or mouse origin. The enzymatic product appears to be primarily the trimer form of 2-5A, rather than a set of oligomers observed in enzymatic reactions performed on IFN-treated cells, including muscle cultures. The kinetics of 2-5A synthetase gene expression revealed that the largest amount of specific RNA transcripts appeared on the 1st day after seeding, followed by a reduction thereafter. In addition, a decrease was also observed in expression of c-myc, a cell-growth-associated protooncogene. However, an increase towards the 2nd day of both AChR and myosin light chain gene expression was evident, indicating selective regulation of gene expression during myogenesis.
Birnbaum
M
M
Department of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Trink
B
B
Shainberg
A
A
Salzberg
S
S
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression; D007372:Interferons / Q000502:physiology*; D051379:Mice; D009132:Muscles / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure; D009218:Myosins / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology
D016271:Proto-Oncogene Proteins c-myc; D011950:Receptors, Cholinergic; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase; D009218:Myosins