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Endoplasmic reticulum stress mediates aristolochic acid I-induced apoptosis in human renal proximal tubular epithelial cells
Zhu S.; Wang Y.; Jin J.; Guan C.; Li M.; Xi C.; Ouyang Z.; Chen M.; Qiu Y.; Huang M.; Huang Z.
2012
Source PublicationToxicology in Vitro
ISSN8872333
Volume26Issue:5Pages:663
AbstractAristolochic acid (AA), derived from the Aristolochia species, has been associated with aristolochic acid nephropathy (AAN), which has emerged as a worldwide disease. Aristolochic acid I (AAI) is the main ingredient of AA, and the underlying mechanisms for AAI-induced nephrotoxicity are still unclear. In this study, we investigated whether endoplasmic reticulum (ER) stress was involved in AAI-induced nephrotoxicity. The results showed that treatment of HK-2 cells (a human proximal tubular epithelial cell line) with AAI caused an increase in eukaryotic initiation factor-2α (eIF2α) phosphorylation, X-box binding protein 1 (XBP1) mRNA splicing and the expression of glucose-regulated protein (GRP) 78 and CAAT/enhancer-binding protein-homologous protein (CHOP). These events represent typical markers of the ER stress-related signaling pathway. Pretreatment with 4-phenylbutyrate (4-PBA) or salubrinal (Sal) significantly inhibited AAI-induced apoptosis, indicating the role of ER stress in AAI-induced apoptosis. In addition, AAI-induced cell death followed an increase of reactive oxygen species (ROS) formation in HK-2 cells. Pretreatment with N-acetyl cysteine (NAC) or glutathione (GSH) significantly inhibited AAI-induced ER stress proteins and cell death, suggesting that ROS mediate AAI-induced ER stress. Taken together, these results suggest that the ER stress response is involved in apoptosis induced by AAI in HK-2 cells, thus offering a new insight into the nephrotoxicity of AAI. © 2012 Elsevier Ltd.
KeywordApoptosis Aristolochic acid I Endoplasmic reticulum stress Oxidative stress
DOI10.1016/j.tiv.2012.03.005
URLView the original
Language英语
The Source to ArticleScopus
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Cited Times [WOS]:33   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
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GB/T 7714
Zhu S.,Wang Y.,Jin J.,et al. Endoplasmic reticulum stress mediates aristolochic acid I-induced apoptosis in human renal proximal tubular epithelial cells[J]. Toxicology in Vitro,2012,26(5):663.
APA Zhu S..,Wang Y..,Jin J..,Guan C..,Li M..,...&Huang Z..(2012).Endoplasmic reticulum stress mediates aristolochic acid I-induced apoptosis in human renal proximal tubular epithelial cells.Toxicology in Vitro,26(5),663.
MLA Zhu S.,et al."Endoplasmic reticulum stress mediates aristolochic acid I-induced apoptosis in human renal proximal tubular epithelial cells".Toxicology in Vitro 26.5(2012):663.
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