title: Stimulation of mechano-growth factor expression by myofibrillar proteins in murine myoblasts and myotubes.
abstract: Mechano-growth factor (MGF) is a product of alternative splicing of the insulin-like growth factor 1 (IGF-1) mRNA. MGF is known to stimulate myoblast proliferation and to protect neurons and cardiomyocytes from apoptosis. MGF expression is dramatically increased in response to mechanical stimuli and tissue damage. The mechanisms of induction of MGF expression are as yet imperfectly understood. There is certain evidence that some protein factors able to stimulate MGF synthesis in normal myoblasts are released from damaged muscle. This study was undertaken to explore the nature of these protein inductors of MGF expression and to investigate the mechanism of their action. We report here that myofibrillar fraction of skeletal muscle homogenate activated MGF expression in murine myoblasts and myotubes in culture. The expression of another splice form of IGF-1 gene, IGF-1Ea, was also stimulated by myofibrils. Three myofibrillar proteins able to stimulate MGF synthesis were isolated. These proteins were identified by MALDI and immunoblotting as myomesin, myosin-binding protein C, and titin. The activation of MGF expression was associated with the increase of cAMP level in the cells. Inhibitor of adenylyl cyclase dideoxyadenosine arrested stimulation of MGF synthesis by all three myofibrillar proteins.
authors.affiliation: A. N. Bach Institute of Biochemistry, Russian Academy of Sciences, Leninskiy Prospect 33, 119071 Moscow, Russia. ivkravchenko@yandex.ru
authors.forename: Irina V
authors.initials: IV
authors.lastname: Kravchenko
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Furalyov
authors.forename: Vladimir O
authors.initials: VO
authors.lastname: Popov
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D064211:Connectin; D003285:Contractile Proteins / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D016048:Dideoxyadenosine / Q000494:pharmacology; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism*; D009210:Myofibrils / Q000187:drug effects / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015854:Up-Regulation; D000099163:Myosin Binding Protein C
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases; D002352:Carrier Proteins; D005576:Colforsin; D064211:Connectin; D003285:Contractile Proteins; D000242:Cyclic AMP; D016048:Dideoxyadenosine; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D007334:Insulin-Like Growth Factor I; D009124:Muscle Proteins; D011494:Protein Kinases; D012333:RNA, Messenger; D000099163:Myosin Binding Protein C; C527564:mechano-growth factor, mouse