Characterisation of ant-1 as an inhibitor of myostatin activity.

• Main Author: Irfana Begum Ikbal.
• Other Authors: Ravi Kambadur
• Format: Final Year Project
• Language: English
• Published: 2011
• Subjects: DRNTU::Science::Biological sciences::Biochemistry
• Online Access: http://hdl.handle.net/10356/45741
• Institution: Nanyang Technological University

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.