Author/Editor     Pegan, Katarina; Matkovič, Urška; Marš, Tomaž; Miš, Katarina; Pirkmajer, Sergej; Brecelj, Janez; Grubič, Zoran
Title     Acetylcholinesterase is involved in apoptosis in the precursors of human muscle regeneration
Type     članek
Source     Chem Biol Interact
Vol. and No.     Letnik 187, št. 1-3
Publication year     2010
Volume     str. 96-100
Language     eng
Abstract     The best established role of acetylcholinesterase (EC 3.1.1.7, AChE) is termination of neurotransmission at cholinergic synapses. However, AChE is also located at sites, where no other cholinergic components are present and there is accumulating evidence for non-cholinergic functions of this protein. In the process of skeletal muscle formation, AChE is expressed already at the stage of mononuclear myoblast, which is long before other cholinergic components can be demonstrated in this tissue. Myoblast proliferation is an essential step in muscle regeneration and is always accompanied by apoptosis. Since there are several reports demonstrating AChE participation in apoptosis one can hypothesize that early AChE expression in myoblasts reflects the development of the apoptotic apparatus in these cells. Here we tested this hypothesis by following the effect of siRNA AChE silencing on apoptotic markers and by determination of AChE level after staurosporine-induced apoptosis in cultured human myoblasts. Decreased apoptosis in siRNA AChE silenced myoblasts and increased AChE expression in staurosporine-treated myoblasts confirmed AChE involvement in apoptosis. The three AChE splice variants were differently affected by staurosporine-induced apoptosis. The hydrophobic (H) variant appeared unaffected, a tendency towards increase of tailed (T) variant was detected, however the highest, 8-fold increase was observed for readthrough (R) variant. In the light of these findings AChE appears to be a potential therapeutic target at muscle injuries including organophosphate myopathy.
Descriptors     ACETYLCHOLINESTERASE
MUSCLE, SKELETAL
APOPTOSIS
STAUROSPORINE
SEQUENCE ANALYSIS, RNA
POLYMERASE CHAIN REACTION
GENE EXPRESSION
FLOW CYTOMETRY
CELLS, CULTURED