Control levels of acetylcholinesterase expression in the mammalian skeletal muscle

Protein expression can be controled at different levels. Understanding acet ylcholinesterase (EC. 3.1.1.7, AChE) expression in the living organisms the refore necessitates: (1) determination and mapping of control levels of ACh E metabolism; (2) identification of the regulatory factors acting at these levels; and (3) detailed insight into the mechanisms of action of these fac tors. Here we summarize the results of our studies on the regulation of ACh E expression in the mammalian skeletal muscle. Three experimental models we re employed: in vitro innervated human muscle, mechanically denervated adul t fast rat muscle, and the glucocorticold treated fast rat muscle. In situ hybridization of AChE mRNA, combined with AChE histochemistry, revealed tha t different distribution patterns of AChE, observed during in vitro ontogen esis and synaptogenesis of human skeletal muscle, reflect alterations in th e distribution of AChE mRNA (Z. Grubic, R. Komel, W.F. Walker, A.F. Miranda , Myoblast fusion and innervation with rat motor nerve alter the distributi on of acetylholinesterase and its mRNA in human muscle cultures, Neuron 14 (1995) 317-327). To study the mechanisms of AChE mRNA loss in denervated ad ult rat skeletal muscle, we exposed deproteinated AChE mRNA to various subc ellular fractions in vitro. Fractions were isolated from the normal and den ervated rat sternomastoideus muscle. We found significantly increased, but non-specific AChE mRNA degradation capacities in the three fractions studie d, suggesting that increased susceptibility of muscle mRNA to degradation m ight be at least partly responsible for the decreased AChE mRNA observed un der such conditions (K. Zajc-Kreft, S. Kreft, Z. Grubic, Degradation of ACh E mRNA in the normal and denervated rat skeletal muscle, Book of Abstracts, The Sixth International Meeting on Cholinesterases, La Jolla, CA, March 20 -24, 1998, p. A3.). In adult fast rat muscle, treated chronically with gluc ocorticoids, we found the fraction of early synthesized ACHE molecular form s to be reduced and AChE mRNA unchanged. This observation is consistent wit h the explanation that translation and/or early post-translational processe s are impaired under such conditions (M. Brank, K. Zajc-Kreft, S. Kreft, R. Komel, Z. Grubic, Biogenesis of acetylcholinesterase is impaired, although its mRNA level remains normal, in the glucocorticoid-treated rat skeletal muscle, fur. J. Biochem. 251 (1998) 374-381). The AChE mRNA level is theref ore important but not the only control level of AChE expression in the mamm alian skeletal muscle. (C) 1999 Elsevier Science Ireland Ltd. All rights re served.