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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
1-Deoxynojirimycin / pharmacology*
-
Apoptosis
-
Carcinoma, Hepatocellular / enzymology*
-
Caspases / metabolism
-
DNA-Binding Proteins / metabolism
-
Endoplasmic Reticulum / drug effects*
-
Endoplasmic Reticulum / enzymology
-
Endoplasmic Reticulum Chaperone BiP
-
Enzyme Inhibitors / pharmacology*
-
Heat-Shock Proteins / metabolism
-
Humans
-
Liver Neoplasms / enzymology*
-
Mannosidases / antagonists & inhibitors*
-
Molecular Chaperones / metabolism
-
Nuclear Proteins / metabolism
-
Protein Folding
-
Regulatory Factor X Transcription Factors
-
Transcription Factors
-
Up-Regulation
-
X-Box Binding Protein 1
Substances
-
DNA-Binding Proteins
-
Endoplasmic Reticulum Chaperone BiP
-
Enzyme Inhibitors
-
HSPA5 protein, human
-
Heat-Shock Proteins
-
Molecular Chaperones
-
Nuclear Proteins
-
Regulatory Factor X Transcription Factors
-
Transcription Factors
-
X-Box Binding Protein 1
-
XBP1 protein, human
-
1-Deoxynojirimycin
-
Mannosidases
-
mannosyl-oligosaccharide 1,2-alpha-mannosidase
-
Caspases