1-Deoxymannojirimycin, the alpha1,2-mannosidase inhibitor, induced cellular endoplasmic reticulum stress in human hepatocarcinoma cell 7721

Biochemical and Biophysical Research Communications
Yi LuZong-Hou Shen

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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Citations

Mar 25, 2014·European Journal of Pharmacology·Jingjing ZhuXin-Shan Ye
Jul 21, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ammad Ahmad FarooqiHsueh-Wei Chang
Oct 31, 2019·Journal of Oncology·Gábor TaxPietro Roversi

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