High glucose‐induced oxidative stress causes apoptosis in proximal tubular epithelial cells and is mediated by multiple caspases

• Published in: The FASEB journal 2003-05, Vol.17 (8), p.1-21
• Main Authors: Allen, David A., Harwood, Steven M., Varagunam, Mira, Raftery, Martin J., Yaqoob, Muhammad M.
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Apoptosis - drug effects; Aspartic Acid - analogs & derivatives; Aspartic Acid - pharmacology; Azoles - pharmacology; Caspase Inhibitors; Caspases - metabolism; cell death; Cell Line; Cysteine Proteinase Inhibitors - pharmacology; diabetic nephropathy; Dose-Response Relationship, Drug; ebselen; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Glucose - pharmacology; Kidney Tubules, Proximal - cytology; Kidney Tubules, Proximal - drug effects; Kidney Tubules, Proximal - metabolism; Nitrites - metabolism; Oligopeptides - pharmacology; Organoselenium Compounds - pharmacology; Oxidative Stress - drug effects; peroxynitrite; Peroxynitrous Acid - antagonists & inhibitors; Peroxynitrous Acid - metabolism
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.02-0130fje

ABSTRACT Diabetic nephropathy is the leading cause of end‐stage renal disease in the Western world. Poor glycemic control contributes to the development of diabetic nephropathy, but the mechanisms underlying high glucose‐induced tissue injury are not fully understood. In the present study, the effect of high glucose on a proximal tubular epithelial cell (PTEC) line was investigated. Reactive oxygen species (ROS) were detected using the fluorescent probes dichlorofluorescein diacetate, dihydrorhodamine 123, and 2,3‐diaminonapthalene. Peroxynitrite (ONOO−) generation and nitrite concentrations were increased after 24 h of high glucose treatment (P