Injury-specific expression of activating transcription factor-3 in retinal ganglion cells and its colocalized expression with phosphorylated c-Jun.
OBJECTIVE
To ascribe activating transcription factor (ATF)-3 as a specifically induced transcription factor after ON injury and to describe its putative role as a modulator of c-Jun transactivation.


METHODS
The adult rat optic nerve was crushed intraorbitally, and expression profiles of ATF-3, ATF-2, and phosphorylated c-Jun (p-c-Jun) were examined by immunohistochemistry and ISH. Western blot analysis for ATF-3 and -2 were also performed. Furthermore, colocalized detection of c-Jun mRNA with ATF-2 or -3 was attempted with a combined method of simultaneous immunohistochemistry and in situ hybridization.


RESULTS
In response to optic nerve injury, substantial expression of ATF-3 as well as that of p-c-Jun was observed in the retinal ganglion cells, whereas no expression of ATF-3 was seen in other noninjured retinal cells. In contrast, ATF-2 was normally expressed abundantly in both retinal ganglion cells and displaced amacrine cells, but expression dropped in retinal ganglion cells after nerve injury. The expression profiles of ATF-2 and -3 after optic nerve injury were confirmed by Western blot analysis. A higher degree of colocalization was observed for ATF-3 and c-Jun than the modest codetection for ATF-2 and c-Jun.


CONCLUSIONS
The transcription factor ATF-3 is specifically induced upon optic nerve injury and colocalizes with p-c-Jun in surviving ganglion cells. These findings suggest that both ATF-3 and c-Jun are crucial to trigger various transcriptional responses and may act synergistically during the survival phase of the optic nerve in the injury model.
Takeda
M
M
Department of Anatomy, Asahikawa Medical College, Hokkaido, Japan.
Kato
H
H
Takamiya
A
A
Yoshida
A
A
Kiyama
H
H
D051698:Activating Transcription Factor 2; D051700:Activating Transcription Factor 3; D000818:Animals; D015153:Blotting, Western; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D016350:Leucine Zippers; D008297:Male; D009409:Nerve Crush; D020221:Optic Nerve Injuries / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis*; D015533:Transcriptional Activation
D051698:Activating Transcription Factor 2; D051700:Activating Transcription Factor 3; C497107:Atf2 protein, rat; C497108:Atf3 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014157:Transcription Factors