Characterisation of ant-1 as an inhibitor of myostatin activity.
Irfana Begum Ikbal.
Date of Issue2011
School of Biological Sciences
Ant-1 is a mimetic peptide of the mature C-terminal region of Myostatin. It has previously been demonstrated to have Myostatin antagonistic activity as proven by increasing satellite cell activation and macrophage infiltration during skeletal muscle regeneration. Furthermore, Ant-1 also increased myogenesis in aged mice. Here, we have attempted to further characterize Ant-1 as an inhibitor of Myostatin. Biacore experiments showed that Ant-1 binds strongly to ActRIIB with an affinity of 5.34nM. Therefore, Ant-1 may potentially act as a competitive inhibitor of Myostatin by binding to ActRIIB, which is a predominant receptor to Myostatin. Moreover, we also found that Ant- 1 treatment reduced Smad3 phosphorylation, thereby reducing Smad3 transactivation activity in a promoter-reporter assay. Consistent with this, we found that Ant-1 increased the proliferation rate of myoblasts and in differentiation as confirmed by increased expression of differentiation markers. Moreover, a short-term treatment of Ant-1 enhanced insulin sensitivity in young wild type mice similar to that seen in Myostatin-null mice. Collectively, we propose that Ant-1 is an inhibitor of Myostatin activity and can be further developed as a drug to treat diseases that are promoted by Myostatin.
Final Year Project (FYP)
Nanyang Technological University