Characterization of apoptosis-genes associated with NMDA mediated cell death in the adult rat retina.
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.
Laabich
A
A
Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, 500 South Preston St., Louisville, KY 40202, USA.
Li
G
G
Cooper
N G
NG
D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D053222:Fas Ligand Protein; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics; D016202:N-Methylaspartate / Q000633:toxicity*; D009474:Neurons; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000494:pharmacology; D011506:Proteins / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I; D012160:Retina / Q000473:pathology* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D000097642:GADD45 Proteins
D015703:Antigens, CD; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D018690:Excitatory Amino Acid Agonists; D053222:Fas Ligand Protein; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D016202:N-Methylaspartate; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010455:Peptides; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D051742:Transcription Factor CHOP; D014157:Transcription Factors; D000097642:GADD45 Proteins; C497251:Ddit3 protein, rat; C505662:Faslg protein, rat; C539820:Nr4a1 protein, rat; C085903:autocamtide-2