title: Reactive oxygen species-mediated endoplasmic reticulum stress contributes to aldosterone-induced apoptosis in tubular epithelial cells.
abstract: Apoptosis contributes to tubular epithelial cell death and atrophy in aldosterone (Aldo)-induced renal injury. This study aimed to determine mechanisms underlying Aldo-induced reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress in tubular epithelial cells. Intracellular ROS generation was evaluated by 2',7'-dichlorofluorescin diacetate fluorescence. Apoptosis was detected by annexin V/propidium iodide staining and flow cytometry. ER stress induced protein and mRNA were evaluated by Western blot and real-time PCR, respectively. Aldo promoted tubular epithelial cell apoptosis, increased intracellular ROS production and induced ER stress, as evidenced by increased expression of glucose-regulated protein 78 (GRP78) and CAAT/enhancer-binding protein homologous protein (CHOP) in a dose- and time-dependent manner. Additionally, siRNA knockdown of CHOP and antioxidant N-acetyl-l-cysteine (NAC) attenuated ER stress-mediated apoptosis. NAC also could inhibit Aldo-induced expression of GRP78 and CHOP. Altogether, these observations suggest that Aldo induces apoptosis via ROS-mediated, CHOP-dependent activation in renal tubular epithelial cells.
authors.affiliation: Division of Nephrology, Huashan Hospital and Institute of Nephrology, Fudan University, 12 Wulumuqi Road, Shanghai 200040, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Minmin
authors.initials: M
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000450:Aldosterone / Q000494:pharmacology / Q000502:physiology*; D017304:Annexin A5 / Q000737:chemistry; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005452:Fluoresceins / Q000737:chemistry; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011419:Propidium / Q000737:chemistry; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051742:Transcription Factor CHOP / Q000096:biosynthesis / Q000235:genetics
chemical_list: D017304:Annexin A5; D000975:Antioxidants; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D005452:Fluoresceins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051742:Transcription Factor CHOP; C029569:diacetyldichlorofluorescein; D011419:Propidium; D000450:Aldosterone; D000111:Acetylcysteine