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

Toxicol Appl Pharmacol. 2008 Dec 1;233(2):220-6. doi: 10.1016/j.taap.2008.09.002. Epub 2008 Sep 12.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • 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
  • Flavonoids / pharmacology
  • Glycation End Products, Advanced / metabolism*
  • Hypertrophy / etiology*
  • Indoles / pharmacology
  • Kidney Tubules / cytology
  • Kidney Tubules / pathology
  • LLC-PK1 Cells
  • Phenols / pharmacology
  • Proto-Oncogene Proteins B-raf / metabolism
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / drug effects
  • Receptors, Immunologic / metabolism
  • Swine
  • Taurine / pharmacology*

Substances

  • 5-iodo-3-((3,5-dibromo-4-hydroxyphenyl)methylene)-2-indolinone
  • Antioxidants
  • Collagen Type IV
  • Fibronectins
  • Flavonoids
  • Glycation End Products, Advanced
  • Indoles
  • Phenols
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • Cyclin-Dependent Kinase Inhibitor p27
  • Taurine
  • Proto-Oncogene Proteins B-raf
  • Extracellular Signal-Regulated MAP Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one