title: Andrographolide-induced apoptosis in human renal tubular epithelial cells: Roles of endoplasmic reticulum stress and inflammatory response.
abstract: Andrographolide sodium bisulfate as a kind of soluble derivative of andrographolide (AD), is obviously known to be nephrotoxicity, but AD has not 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.
authors.affiliation: School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Gu
authors.affiliation: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 31003, Zhejiang Province, China.
authors.forename: Xin-Yue
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China.
authors.forename: Wen-Min
authors.initials: WM
authors.lastname: Xing
authors.affiliation: School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China.
authors.forename: Jia-Dong
authors.initials: JD
authors.lastname: Xu
authors.affiliation: School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China. Electronic address: luhong03@hotmail.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D004224:Diterpenes / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000276:immunology; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000096:biosynthesis; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D007684:Kidney Tubules / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015394:Molecular Structure; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D004224:Diterpenes; D000091342:Endoplasmic Reticulum Chaperone BiP; C491143:HAVCR1 protein, human; C000717247:HSPA5 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C030419:andrographolide
keywords: Andrographolide; Endoplasmic reticulum stress; Inflammation; Oxidative stress; Renal toxicity