Characterization of apoptosis-genes associated with NMDA mediated cell death in the adult rat retina

Brain Res Mol Brain Res. 2001 Jul 13;91(1-2):34-42. doi: 10.1016/s0169-328x(01)00116-4.

Abstract

Calcium/calmodulin-dependent protein kinase II containing a nuclear localizing signal (CaMKII-alphaB) is altered in retinal neurons exposed to N-methyl-D-aspartate (NMDA). AIP (myristoylated autocamtide-2-related inhibitory peptide), a specific inhibitor of CaMKII provides neuroprotection against NMDA-mediated neurotoxicity. In this study, gene-arrays were used to investigate which apoptosis-associated genes are altered after exposure to NMDA. The data indicate an increased expression (2-7-fold) of five such genes encoding proteins that could be involved in NMDA induced cell death. The up-regulated genes are: FasL; GADD45; GADD153; Nur77 and TNF-R1. Treatment with AIP blocked their altered expression. The results suggest that multiples genes are involved in NMDA-induced excitotoxicity and that AIP, a specific inhibitor for CaMKII, regulates the expression of these apoptosis-associated genes in the retina.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • CCAAT-Enhancer-Binding Proteins / genetics
  • DNA-Binding Proteins / genetics
  • Excitatory Amino Acid Agonists / toxicity*
  • Fas Ligand Protein
  • Female
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins / genetics
  • N-Methylaspartate / toxicity*
  • Neurons
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Oligonucleotide Array Sequence Analysis
  • Peptides / pharmacology
  • Proteins / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor, Type I
  • Retina / pathology*
  • Retina / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factor CHOP
  • Transcription Factors / genetics
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / physiology

Substances

  • Antigens, CD
  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Ddit3 protein, rat
  • Excitatory Amino Acid Agonists
  • Fas Ligand Protein
  • Faslg protein, rat
  • GADD45 protein
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Nr4a1 protein, rat
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Peptides
  • Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Transcription Factors
  • autocamtide-2
  • Transcription Factor CHOP
  • N-Methylaspartate