Induction of apoptosis in human renal tubular epithelial HK-2 cells by emodin and mediation of endoplasmic reticulum stress / 中草药

ABSTRACT

Objective: To investigate the induetion of apoptosis in human renal tubular epithelial HK-2 cells by emodin and whether endoplasmic reticulum (ER) stress is involved in its mechanism. Methods: HK-2 cells were cultured and treated with various concentration of emodin at different time points. The cell viability was determined by MTT assay. The gene expression of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein-homologous protein (CHOP), activating transcription factor 3 (ATF3), and X-box binding protein 1 splicing (XBP1s) was evaluated by quantitative real-time PCR. The protein expression of caspase-3, GRP78, CHOP, and eukaryotic initiation factor 2 alpha (eIF2α) was detected by Western blotting. Results: The viability of HK-2 cells was decreased by emodin in a dose-dependent manner, and the apoptosis of the cells was associated with caspase-3 shear activation. The treatment with emodin in HK-2 cells caused the increase in eIF2α phosphorylation, XBP1 mRNA splicing, the gene expression of GRP78, CHOP, and ATF3, and the protein expression of GRP78 and CHOP. The pretreatment with 4-phenylbutyric acid and salubrinal significantly increased the viability of HK-2 cells, indicating the role of ER stress in emodin-induced apoptosis. Conclusion: Emodin induces the apoptosis in HK-2 cells and ER stress is involved in emodin-induced apoptosis.