ACTIN CYTOSKELETON AS A TARGET FOR 2-CHLORO ADENOSINE - EVIDENCE FOR INDUCTION OF APOPTOSIS IN C2C12 MYOBLASTIC CELLS

Recent results for various cell types have shown that adenosine is cap able of inducing relevant cytophatological alterations which can event ually lead to apoptosis. No da,ta are available regarding the involvem ent of adenosine in apoptosis of muscle cells. In this work, we studie d the effect of the relatively hydrolysis-resistant adenosine analog a chloro adenosine on a cultured myogenic cell line, C2C12, which is ab le to differentiate in vitro, leading to the formation of syncythia, g iant multinucleated cells called myotubes. Results indicated that a-ch loro adenosine induces apoptotic cell death. in both myoblasts and myo tubes; this was preceded by a derangement of actin microfilaments, whi ch represent the main cytoskeletal component and play a pivotal role i n the physiology of such cell. line. The time-dependency of cytoskelet al alterations suggested a causal relationship between these changes a nd the induction of apoptosis. These results implicate adenosine as an endogenous regulator of apoptosis in muscle cells and validate this c ell model system as a useful tool for studying human muscle cell patho logies. (C) 1997 Academic Press.