Lysosomal enzyme cathepsin B is involved in kainic acid-induced excitotoxicity in rat striatum

Brain Res. 2006 Feb 3;1071(1):245-9. doi: 10.1016/j.brainres.2005.10.074. Epub 2006 Jan 10.

Abstract

The present study investigated the role of lysosomal enzymes in excitotoxic neuronal damage induced by excessive stimulation of non-NMDA glutamate receptors with kainic acid (KA). Internucleosomal DNA fragmentation was induced after intrastriatal administration of KA 1.25-5.0 nmol to rats. Increased expression of cathepsin B (P < 0.01, n = 6) but not cathepsin L in KA-injected striatum was observed 12 to 24 h after intrastriatal infusion of KA (2.5 nmol). Treatment with intrastriatal infusion of the cathepsin B inhibitor Z-FA-FMK (5-10 microg) 10 min prior to or 3 h after KA injection robustly attenuated KA-induced (2.5 nmol) DNA fragmentation. Z-FA-FMK (10 microg) also significantly reduced the size of striatal lesions induced by KA (P < 0.01, n = 6). These results suggest that lysosomal enzyme cathepsin B plays an important role in excitotoxic neuronal injury.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western / methods
  • Cathepsin B / antagonists & inhibitors
  • Cathepsin B / metabolism*
  • Corpus Striatum / drug effects*
  • Corpus Striatum / injuries
  • DNA Fragmentation / drug effects
  • Dipeptides / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Electrophoresis, Agar Gel / methods
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Agonists / toxicity*
  • Gene Expression / drug effects
  • Kainic Acid / toxicity*
  • Ketones / pharmacology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Dipeptides
  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Ketones
  • MDL 201053
  • Cathepsin B
  • Kainic Acid