New Caspases’inhibitors belonging to the serpin superfamily:A novel key control point of apoptosis in mammalian tissues

摘要

The present report overviews a new family of bovine serpins able to inhibit pseudo-irreversibly initiator and effector caspases, a group of cysteine proteases in charge of cell dismantling during apoptosis, a finely regulated cell death process. The 8 members identified at the gene level showed a high homology with human SERPINA3 and were therefore designed bovSERPINA3-1 to A3-8. At least six of them are able to inhibit caspases. Two of them (bovSERPINA3-1 and A3-3) have been purified from bovine muscle and extensively investigated during these last years. After a general presentation of the serpin superfamily, the kinetic aspects of their interaction with human cas-pases 3 and 8 were studied and findings obtained suggest that caspases could be their target enzymes in living cells. In muscle and primary myoblast in culture, they showed an intracellular localization and because of their high level in blood, they can be exported. Two biological functions (potential regulator of apoptosis and expression during myoblast differentiation) were investigated and it was concluded that they are very likely a efficient regulator of apoptosis, a proposal supported by their high expression in proliferating myoblast (cell survival is essential during this differentiation phase) but not in myotubes.