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.
Department of Anatomy, Asahikawa Medical College, Hokkaido, Japan.
M
M
Takeda
H
H
Kato
A
A
Takamiya
A
A
Yoshida
H
H
Kiyama
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