Document Detail

The endoplasmic reticulum stress response is involved in apoptosis induced by aloe-emodin in HK-2 cells.
MedLine Citation:
PMID:  22210228     Owner:  NLM     Status:  MEDLINE    
Aloe-emodin (AE; 1,8-dihydroxy-3-hydroxymethyl-9,10-anthracenedione) is one of the primary active compounds in total rhubarb anthraquinones (TRAs), which induce nephrotoxicity in rats. However, it is still not known whether AE has a similar effect on human kidney cells. In this study, 3-(4,5,-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays showed that AE decreases the viability of HK-2 cells (a human proximal tubular epithelial cell line) in a dose- and time-dependent manner. AE induced G2/M arrest of cell cycle in HK-2 cells, which was detected with propidium iodide (PI) staining. This apoptosis was further investigated by Hoechst staining, transmission electron microscopy (TEM), DNA fragmentation, and Annexin V/PI staining. Apoptosis of the cells was associated with caspase 3 activation, which was detected by Western blot analysis and a caspase activity assay. In addition, changes in the endoplasmic reticulum (ER) ultrastructure as observed by TEM showed the effects of AE on ER. Treatment with AE also resulted in an increase in eukaryotic initiation factor-2α (eIF-2α) phosphorylation, X-box binding protein 1 (XBP1) mRNA splicing, c-Jun N-terminal kinase (JNK) phosphorylation, glucose-regulated protein (GRP) 78 and CAAT/enhancer-binding protein-homologous protein (CHOP) accumulation. These results suggest that AE induces ER stress in HK-2 cells, which is involved in AE-induced apoptosis. In conclusion, AE induces apoptosis in HK-2 cells, and the ER stress is involved in AE-induced apoptosis in vitro. The implications of the toxic effects of AE for clinical use are unclear and these findings should be taken into account in the risk assessment for human exposure.
Shaohua Zhu; Jing Jin; Yan Wang; Zizhang Ouyang; Chen Xi; Jia Li; Yuwen Qiu; Jinzhi Wan; Min Huang; Zhiying Huang
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Publication Detail:
Type:  Journal Article     Date:  2011-12-21
Journal Detail:
Title:  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association     Volume:  50     ISSN:  1873-6351     ISO Abbreviation:  Food Chem. Toxicol.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-12     Completed Date:  2012-07-16     Revised Date:  2013-02-07    
Medline Journal Info:
Nlm Unique ID:  8207483     Medline TA:  Food Chem Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1149-58     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
School of Pharmaceutical Sciences, Center of Laboratory Animals, Sun Yat-sen University, Guangzhou 510006, PR China.
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MeSH Terms
Anthraquinones / pharmacology*
Apoptosis / drug effects*
Base Sequence
Blotting, Western
Cell Cycle / drug effects
Cell Line
Cell Survival / drug effects
DNA Primers
DNA-Binding Proteins / genetics
Endoplasmic Reticulum / drug effects*,  metabolism,  ultrastructure
Fluorescent Antibody Technique
Gene Expression / drug effects
Microscopy, Electron, Transmission
RNA Splicing
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors / genetics
Reg. No./Substance:
0/Anthraquinones; 0/DNA Primers; 0/DNA-Binding Proteins; 0/RNA, Messenger; 0/Transcription Factors; 0/regulatory factor X transcription factors; C8IYT9CR7C/aloe emodin
Comment In:
Food Chem Toxicol. 2013 Jan;51:458   [PMID:  22760114 ]

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