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.

Potential effect of mechano growth factor E-domain peptide on axonal guidance growth in primary cultured cortical neurons of rats

“…Here, we have shown that, in agreement with a previous study (Kravchenko et al , ), MGF‐Ct24E can promote cell viability after nerve injury in the primary cultured cortical neurons, thus exhibiting a protective role against neuronal apoptosis. Furthermore, we demonstrate that MGF‐Ct24E can promote axonal connection and elongation (Figure ), but cell density decreased significantly after MGF‐Ct24E treatment at 0.05, 0.1, 0.5 and 1.0 μg/ml.…”

“…Previous studies of MGF and its E‐domain peptide were mainly focused on bone transplantation or rehabilitation, and fewer reports have been concentrated on neuroscience (Kravchenko et al , ; Riddoch‐Contreras et al , ). MGF and MGF‐Ct24E have been implicated in neuronal development, maintenance and neuroprotection, but the certain mechanism needs to be investigated.…”

“…Further studies reveal that the neuroprotective role of MGF may be independent from the IGF‐1 receptor (Dluzniewska et al , ), despite the fact that the accurate mode of action for this molecule mechanism is still not very clear. Although MGF is known to protect neurons from apoptosis (Beresewicz et al , ; Kravchenko et al , ), there are few reports for its protective effect on neuronal regeneration. As a result, its role on neuronal guidance growth has also not been examined.…”

Influence of resistance exercise intensity and metabolic stress on anabolic signaling and expression of myogenic genes in skeletal muscle

“…This finding allows us to conclude that mRNA expression of MGF (IGF‐1Ec) in trained muscle depends on the exercise intensity (comparison of MI and HI) and does not depend on the metabolic stress (comparison of MIR and MI). We have shown previously that myofibrillar proteins (such as myomesin 1, myosin‐binding protein C, and titin) released from damaged cells stimulate MGF expression at both the mRNA and protein levels in primary murine myoblasts or differentiated in vitro myotubes . It is possible to speculate that, in our study, HI induced degradation of myofibrillar proteins, which may stimulate MGF gene expression.…”

DMP‐1 ‐mediated Ghr gene recombination compromises skeletal development and impairs skeletal response to intermittent PTH

“…This effect persisted for 24 h, where Igf1 gene expression increased by 4-fold compared with the control (63). Similarly, in studies of muscle cells, IGF-1 gene and protein expression increased in response to activation of the cAMP/PKA pathway (64,65). Therefore, we assessed whether PTH enhances GHR activation by increasing Ghr, Igf1,o rIgf1r gene expression in IDG-SW3 osteocyte-like cells.…”