Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells

• Published in: Toxicology and applied pharmacology Vol. 233; no. 2; pp. 220 - 226
• Main Authors: Huang, Jau-Shyang, Chuang, Lea-Yea, Guh, Jinn-Yuh, Yang, Yu-Lin, Hsu, Min-Shyang
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.12.2008; Elsevier
• Subjects: 60 APPLIED LIFE SCIENCES; Advanced glycation end products; ALBUMINS; Animals; ANTIOXIDANTS; Antioxidants - pharmacology; APOPTOSIS; Biological and medical sciences; CATTLE; CELL CYCLE; Cell Cycle - drug effects; CELL PROLIFERATION; Cell Proliferation - drug effects; COLLAGEN; Collagen Type IV - drug effects; Collagen Type IV - metabolism; Cyclin-Dependent Kinase Inhibitor p27 - drug effects; Cyclin-Dependent Kinase Inhibitor p27 - metabolism; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - physiopathology; Epithelial Cells - drug effects; Epithelial Cells - pathology; Extracellular Signal-Regulated MAP Kinases - metabolism; Fibronectins - drug effects; Fibronectins - metabolism; FIBROSIS; Flavonoids - pharmacology; Glycation End Products, Advanced - metabolism; HYPERTROPHY; Hypertrophy - etiology; Indoles - pharmacology; INHIBITION; Kidney Tubules - cytology; Kidney Tubules - pathology; KIDNEYS; LACTATE DEHYDROGENASE; LLC-PK1 Cells; Medical sciences; MITOCHONDRIA; NECROSIS; OXYGEN; Phenols - pharmacology; Proto-Oncogene Proteins B-raf - metabolism; Receptor for Advanced Glycation End Products; RECEPTORS; Receptors, Immunologic - drug effects; Receptors, Immunologic - metabolism; Renal tubular epithelial cells; Swine; TAURINE; Taurine - pharmacology; Toxicology; Taurine; Renal tubular epithelial cells; DN; RAGE; MAPK; ECM; BSA; LDH; Advanced glycation end products; ROS; AGE; ERK; Hypertrophy; Renal tubule; Urinary system; Aminoacid; Epithelial cell; In vitro; Kidney
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2008.09.002

Mounting evidence indicates that advanced glycation end products (AGE) play a major role in the development of diabetic nephropathy (DN). Taurine is a well documented antioxidant agent. To explore whether taurine was linked to altered AGE-mediated renal tubulointerstitial fibrosis in DN, we examined the molecular mechanisms of taurine responsible for inhibition of AGE-induced hypertrophy in renal tubular epithelial cells. We found that AGE (but not non-glycated BSA) caused inhibition of cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, bcl-2 protein expression, and mitochondrial cytochrome c release in BSA, AGE, or the antioxidant taurine treatments in these cells. AGE-induced the Raf-1/extracellular signal-regulated kinase (ERK) activation was markedly blocked by taurine. Furthermore, taurine, the Raf-1 kinase inhibitor GW5074, and the ERK kinase inhibitor PD98059 may have the ability to induce cellular proliferation and cell cycle progression from AGE-treated cells. The ability of taurine, GW5074, or PD98059 to inhibit AGE-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of RAGE, p27 Kip1, collagen IV, and fibronectin. The results obtained in this study suggest that taurine may serve as the potential anti-fibrotic activity in DN through mechanism dependent of its Raf-1/ERK inactivation in AGE-induced hypertrophy in renal tubular epithelial cells.