Characterisation of ant-1 as an inhibitor of myostatin activity.
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 my...
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| Format: | Final Year Project (FYP) |
| Language: | English |
| Published: |
2011
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| Online Access: | http://hdl.handle.net/10356/45741 |
| _version_ | 1826127068193095680 |
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| author | Irfana Begum Ikbal. |
| author2 | Ravi Kambadur |
| author_facet | Ravi Kambadur Irfana Begum Ikbal. |
| author_sort | Irfana Begum Ikbal. |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T07:02:44Z |
| format | Final Year Project (FYP) |
| id | ntu-10356/45741 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:02:44Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | ntu-10356/457412023-02-28T17:59:37Z Characterisation of ant-1 as an inhibitor of myostatin activity. Irfana Begum Ikbal. Ravi Kambadur School of Biological Sciences DRNTU::Science::Biological sciences::Biochemistry 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. Bachelor of Science in Biological Sciences 2011-06-16T08:42:44Z 2011-06-16T08:42:44Z 2011 2011 Final Year Project (FYP) http://hdl.handle.net/10356/45741 en Nanyang Technological University 29 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences::Biochemistry Irfana Begum Ikbal. Characterisation of ant-1 as an inhibitor of myostatin activity. |
| title | Characterisation of ant-1 as an inhibitor of myostatin activity. |
| title_full | Characterisation of ant-1 as an inhibitor of myostatin activity. |
| title_fullStr | Characterisation of ant-1 as an inhibitor of myostatin activity. |
| title_full_unstemmed | Characterisation of ant-1 as an inhibitor of myostatin activity. |
| title_short | Characterisation of ant-1 as an inhibitor of myostatin activity. |
| title_sort | characterisation of ant 1 as an inhibitor of myostatin activity |
| topic | DRNTU::Science::Biological sciences::Biochemistry |
| url | http://hdl.handle.net/10356/45741 |
| work_keys_str_mv | AT irfanabegumikbal characterisationofant1asaninhibitorofmyostatinactivity |