(-)-Epigallocatechin gallate attenuates glutamate-induced cytotoxicity via intracellular Ca modulation in PC12 cells

Clin Exp Pharmacol Physiol. 2004 Aug;31(8):530-6. doi: 10.1111/j.1440-1681.2004.04044.x.

Abstract

1. The effects of (-)-epigallocatechin gallate (EGCG), a green tea polyphenol, on glutamate-induced increases in intracellular Ca2+ concentrations ([Ca2+]i) and cytotoxicity in PC12 cells were investigated. 2. Changes in [Ca2+]i were measured using Fura-2/AM calcium indicator dye and cellular viabilities were determined by a viable cell count and a 3-(4,4-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. 3. Glutamate increased [Ca2+]i in PC12 cells in a dose-dependent manner. (-)-Epigallocatechin gallate attenuated this glutamate (30 mmol/L)-induced [Ca2+]i increase and EGCG (50 micromol/L) increased the viability of PC12 cells against glutamate-induced cytotoxicity. The EGCG effect was also found to be independent of its general anti-oxidant mechanism. In contrast, EGCG directly suppressed both N-methyl-D-aspartate (50 mmol/L)- and kainate (20 mmol/L)-mediated Ca2+ influx, but not metabotropic receptor-mediated Ca2+ release. 4. These results suggest that EGCG reduces the glutamate-induced [Ca2+]i increase by attenuating ionotropic Ca2+ influx and that this promotes the viability of PC12 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / antagonists & inhibitors
  • Calcium / metabolism*
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology*
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Glutamic Acid / toxicity*
  • Intracellular Fluid / drug effects*
  • Intracellular Fluid / metabolism*
  • PC12 Cells
  • Rats

Substances

  • Excitatory Amino Acid Antagonists
  • Glutamic Acid
  • Catechin
  • epigallocatechin gallate
  • Calcium