Effect of Advanced Glycation End Products on Oxidative Stress and Senescence of Trabecular Meshwork Cells

• Published in: Korean journal of ophthalmology Vol. 26; no. 2; pp. 123 - 131
• Main Authors: Park, Cheul Ho, Kim, Jae Woo
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Ophthalmological Society 01.04.2012; 대한안과학회
• Subjects: Acetylcysteine - metabolism; Apoptosis - drug effects; Apoptosis - physiology; Arginine - metabolism; Cell Survival - drug effects; Cell Survival - physiology; Cells, Cultured; Cellular Senescence - drug effects; Cellular Senescence - physiology; Glycation End Products, Advanced - metabolism; Glycation End Products, Advanced - toxicity; Humans; Nitric Oxide - metabolism; Original; Oxidative Stress - physiology; Pterins - metabolism; Reactive Oxygen Species - metabolism; Serum Albumin, Bovine - metabolism; Serum Albumin, Bovine - toxicity; Trabecular Meshwork - drug effects; Trabecular Meshwork - metabolism; Trabecular Meshwork - pathology; 안과학; Antioxidants; Aging; Oxidative stress; Trabecular meshwork cells; Advanced glycation end products
• ISSN: 1011-8942; 2092-9382; 2092-9382
• DOI: 10.3341/kjo.2012.26.2.123

To investigate the effect of advanced glycation end products (AGE) on oxidative stress and cellular senescence in cultured human trabecular meshwork cells (HTMC). Primarily cultured HTMC were exposed to 0, 10, 50, 100, 200 µg/mL of glycated bovine serum albumin (G-BSA) for 5 days. Also co-exposed were L-arginine, sepiapterin, and antioxidant N-acetylcysteine (NAC). Cellular survival and production of nitric oxide (NO), superoxide, and reactive oxygen species were assessed by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide assay, Griess assay, cytochrome c assay, and dichlorofluorescin diacetate assay, respectively. Senescence-associated β-galactosidase staining was performed to quantify the degree of cellular senescence. G-BSA decreased cellular survival, NO production, and increased superoxide production significantly in a dose-dependent manner. The effects of G-BSA were abolished with co-exposure of L-arginine, sepiapterin, and NAC. G-BSA enhanced cellular senescence accompanied by increased production of reactive oxygen species. G-BSA-induced cellular senescence was suppressed by application of L-arginine, sepiapterin, and NAC. AGE enhances cellular senescence of HTMC accompanied with increased oxidative stress. AGE-induced oxidative stress and cellular senescence could be delayed by application of anti-oxidants.