1-Deoxymannojirimycin, the alpha1,2-mannosidase inhibitor, induced cellular endoplasmic reticulum stress in human hepatocarcinoma cell 7721 |
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Authors: | Lu Yi Xu Ying-Ying Fan Kai-Yi Shen Zong-Hou |
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Institution: | Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, 200032, PR China. |
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Abstract: | Alpha1,2-mannosidases, key enzymes in N-glycan processing and located both in the endoplasmic reticulum and golgi, have been targets in the development of anti-cancer therapies. Previous studies have shown its involvement in protein degradation. In this study, 1-deoxymannojirimycin, a specific inhibitor of alpha1,2-mannosidase and generating 'high mannose' type of N-glycan, was treated in human hepatocarcinoma 7721 cells and induced the endoplasmic reticulum stress. Key moleculars as XBP1 and GRP78/Bip were activated and up-regulated, which suggested the UPR pathway was activated. The cleavage of caspase-12, -9, and -3 was also detected, which implicated the ER stress was triggered and apoptosis occurred in H7721 cells. The results indicate the 'high Man' structure generated by 1-deoxymannojirimycin may constitute potential novel mechanism for ER stress and caspase-12 pathway of cell apoptosis. |
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Keywords: | α1 2-Mannosidase 1-Deoxymannojirimycin Endoplasmic reticulum stress Apoptosis |
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