Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 344, Issue 1, Pages 221-225Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2006.03.111
Keywords
alpha 1,2-mannosidase; 1-deoxymannojirimycin; endoplasmic reticulum stress; apoptosis
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alpha 1,2-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 alpha 1,2-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 XBPI 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. (c) 2006 Elsevier Inc. All rights reserved.
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