Pro-apoptotic role of c-Jun in NMDA-induced neurotoxicity in the rat retina.
We examined the role of c-Jun on N-methyl-D-aspartate (NMDA)-induced neurotoxicity in the rat retina. An increase in c-Jun mRNA, c-Jun protein and phosphorylated c-Jun (p-c-Jun) levels in the retina was detected 3 hr after intravitreal injection of NMDA (20 nmol). These levels peaked after 12 hr, and then returned to their control levels by 24 hr. c-Jun and p-c-Jun immunoreactivities were observed in the retinal ganglion cell layer (RGCL), especially in retinal ganglion cells (RGCs), and in the inner nuclear layer (INL) 12 hr after NMDA injection, and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL)-positive cells were immunopositive for c-Jun and p-c-Jun. A c-Jun antisense oligodeoxynucleotide (AS ODN), which was simultaneously injected with NMDA, penetrated the cells in the RGCL and the INL, suppressed the NMDA-induced increase in c-Jun and p-c-Jun protein levels and reduced the number of TUNEL-positive cells in the RGCL 12 hr after the injection. The protective effect of c-Jun AS ODN on the NMDA-treated retina was also shown by the RGCL cell count and measurement of the IPL thickness, as well as by quantitative real-time PCR analysis of Thy-1 mRNA 7 days after the injection. These results suggest that c-Jun synthesis and phosphorylation participate in NMDA-induced neuronal cell death.
Department of Ophthalmology, St. Marianna University School of Medicine, Kawasaki-shi, Kanagawa, Japan. munemasa@marianna-u.ac.jp
Yasunari
Y
Munemasa
Ritsuko
R
Ohtani-Kaneko
Yasushi
Y
Kitaoka
Toshio
T
Kumai
Yuka
Y
Kitaoka
Yasuhiro
Y
Hayashi
Minoru
M
Watanabe
Hiroyuki
H
Takeda
Kazuaki
K
Hirata
Satoki
S
Ueno
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D016202:N-Methylaspartate / Q000633:toxicity*; D020319:Oligodeoxyribonucleotides, Antisense; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D051381:Rats; D012160:Retina / Q000187:drug effects / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D018690:Excitatory Amino Acid Agonists; D020319:Oligodeoxyribonucleotides, Antisense; D016755:Proto-Oncogene Proteins c-jun; D016202:N-Methylaspartate