title: Inhibition of myostatin signaling through Notch activation following acute resistance exercise.
abstract: Myostatin is a TGFβ family member and negative regulator of muscle size. Due to the complexity of the molecular pathway between myostatin mRNA/protein and changes in transcription, it has been difficult to understand whether myostatin plays a role in resistance exercise-induced skeletal muscle hypertrophy. To circumvent this problem, we determined the expression of a unique myostatin target gene, Mighty, following resistance exercise. Mighty mRNA increased by 6 h (82.9 ± 24.21%) and remained high out to 48 h (56.5 ± 19.67%) after resistance exercise. Further examination of the soleus, plantaris and tibialis anterior muscles showed that the change in Mighty mRNA at 6 h correlated with the increase in muscle size associated with this protocol (R(2) = 0.9996). The increase in Mighty mRNA occurred both independent of Smad2 phosphorylation and in spite of an increase in myostatin mRNA (341.8 ± 147.14% at 3 h). The myostatin inhibitor SKI remained unchanged. However, activated Notch, another potential inhibitor of TGFβ signaling, increased immediately following resistance exercise (83 ± 11.2%) and stayed elevated out to 6 h (78 ± 16.6%). Electroportion of the Notch intracellular domain into the tibialis anterior resulted in an increase in Mighty mRNA (63 ± 13.4%) that was equivalent to the canonical Notch target HES-1 (94.4 ± 7.32%). These data suggest that acute resistance exercise decreases myostatin signaling through the activation of the TGFβ inhibitor Notch resulting in a decrease in myostatin transcriptional activity that correlates well with muscle hypertrophy.
authors.affiliation: Division of Molecular Physiology, University of Dundee, Dundee, Scotland, United Kingdom.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: MacKenzie
authors.forename: David Lee
authors.initials: DL
authors.lastname: Hamilton
authors.forename: Mark
authors.initials: M
authors.lastname: Pepin
authors.forename: Amy
authors.initials: A
authors.lastname: Patton
authors.forename: Keith
authors.initials: K
authors.lastname: Baar
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005260:Female; D015870:Gene Expression; D006801:Humans; D006984:Hypertrophy; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D055435:Myostatin / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D051381:Rats; D017208:Rats, Wistar; D051880:Receptors, Notch / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D051899:Smad2 Protein / Q000378:metabolism; D013997:Time Factors
chemical_list: D009124:Muscle Proteins; D055435:Myostatin; D051880:Receptors, Notch; D051899:Smad2 Protein; C497784:Smad2 protein, rat; C528691:mighty protein, mouse