Utilization of kifunensine for increasing high-mannose type N-glycan of acid α-glucosidase

초록

Pompe disease is one of lysosomal storage diseases caused by dysfunction of acid α-glucosidase (GAA). Glycogen accumulation in lysosome due to the lack of GAA causes skeletal and cardiac muscle myopathy. Enzyme replacement therapy is known to be the most effective for the treatment of Pompe disease through mannose 6-phosphate (M6P) pathway. Therefore, production of GAA including high-mannose type N-glycan is important to make M6P structure. Kifunensine, a class I α-mannosidase inhibitor, inhibits mannose hydrolysis step of N-glycan maturation in endoplasminc reticulum and Golgi apparatus. Furthermore, inhibition of mannosidase could reduce plant-specific glycan residues, which are able to induce immunogenicity. In this study, 5, 10, 20 μM kifunensine were applied to transgenic rice cell cultures. Complex type N-glycan of Oryza sativa could be regulated by kifunensine. In conclusion, it was found that kifunensine could be used as a N-glycan regulator during in vitro cell cultures.