Andrographolide-induced apoptosis in human renal tubular epithelial cells: Roles of endoplasmic reticulum stress and inflammatory response

Publication date: Available online 3 June 2016 Source:Environmental Toxicology and Pharmacology Author(s): Li-Li Gu, Xin-Yue Zhang, Wen-Min Xing, Jia-Dong Xu, Hong Lu Andrographolide sodium bisulfate as a kind of soluble derivative of andrographolide(AD), is obviously known to be nephrotoxicity, but AD hasn’t been reported clearly. Our study aimed to investigate the induction of apoptosis in human renal tubular epithelial (HK-2) cells by AD and its possible mechanism. Our results demonstrated that AD (0∼250μmol/L) inhibited Hk-2 cells proliferation in a dose- and time-dependent manner and induced apoptosis, accompanied by decreased of superoxide dismutase (SOD) activity and increased of malondialdehvde (MDA) content. Simultaneously, AD regulated the expression of endoplasmic reticulum (ER) molecular chaperone glucose-regulated protein 78 (GRP78/Bip) protein, elevated the expressions of C/EBP homologous protein (CHOP) and Caspase-4, indicating activation of ER stress signaling, and induced the alterative expression of kidney injury molecule-1(KIM-1), tumor necrosis factor-α(TNF-α) and Interleukin-6(IL-6) proteins. It provided evidence that ER stress and inflammation would be significant mechanisms responsible for AD-induced apoptosis in addition to oxidative stress. Graphical abstract
Source: Environmental Toxicology and Pharmacology - Category: Environmental Health Source Type: research