Apoptosis induced by all-trans retinoic acid in N-acetylglucosaminyltransferase V repressed human hepatocarcinoma cells is mediated through endoplasmic reticulum stress

✍ Scribed by Ying-Ying Xu; Yi Lu; Kai-Yi Fan; Zong-Hou Shen

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 283 KB
• Volume: 100
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.21088

✦ Synopsis

Abstract

We previously demonstrated that endoplasmic reticulum (ER) stress was triggered in human hepatocarcinoma 7721 cells transfected with antisense cDNA of N‐acetylglucosaminyltransferase V (GnT‐V‐AS/7721) which were more susceptible to apoptosis induced by all‐trans retinoic acid (ATRA). In the present study, we report that ATRA‐induced apoptosis in GnT‐V‐AS/7721 cells is mediated through ER stress. We show here that ER stress is enhanced in GnT‐V‐AS/7721 cells with 80 µM ATRA treatment for 24 h, which is evidenced by the increase of GRP78/Bip, C/EBP‐homologous protein‐10 (CHOP, also known as GADD153) and spliced XBP1. Additionally, activation of caspase‐12, caspase‐9, and ‐3 was detected, and apoptosis morphology was observed in GnT‐V‐AS/7721 cells with ATRA treatment. These results suggest that ATRA enhances the ER stress triggered in GnT‐V‐AS/7721 cells, which represents a novel mechanism of ATRA to induce apoptosis. We further observed that GnT‐V was significantly repressed and the structure of N‐glycans was changed in GnT‐V‐AS/7721 cells with 80 µM ATRA treatment for 24 h, suggesting that repression of GnT‐V by ATRA causes the enhanced ER stress and ER stress‐mediated apoptosis in GnT‐V‐AS/7721 cells. J. Cell. Biochem. 100: 773–782, 2007. © 2006 Wiley‐Liss, Inc.