Amino-terminal phosphorylation of c-Jun regulates apoptosis in the retinal ganglion cells by optic nerve transection.
OBJECTIVE
To examine the involvement of c-Jun and c-Jun N-terminal phosphorylation (JNP) in apoptosis of retinal ganglion cells (RGCs) after the optic nerve (ON) transection.


METHODS
The expression and phosphorylation of c-Jun protein and apoptosis in RGCs were examined after ON transection in wild-type mice and mice in which both phosphoacceptor serines of Jun have mutated to alanines (c-Jun[AA] mice). The fluorescent tracer 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) was applied to the superior colliculi (SC), and the right ON was severed after 7 days. After two more weeks, the average number of RGCs per field was calculated.


RESULTS
JNP and TUNEL-labeled apoptotic nuclei were detected in the ganglion cell layer (GCL) of the retina of the wild-type mice in response to ON transection. The numbers of TUNEL-positive nuclei in the c-Jun(AA) mice was reduced in comparison to those in wild-type mice. Retrograde labeling showed that the number of the RGCs in the retinas on the injured side of the c-Jun(AA) mice was significantly higher than in wild-type mice 14 days after the lesion.


CONCLUSIONS
These results suggest that there is a partial but significant contribution of JNP to the induction of apoptosis in RGCs by ON transection.
Yoshida
Kazuhiko
K
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California-San Diego, La Jolla, CA, USA. kyoshida@med.hokudai.ac.jp
Behrens
Axcel
A
Le-Niculescu
Helen
H
Wagner
Erwin F
EF
Harada
Takayuki
T
Imaki
Junko
J
Ohno
Shigeaki
S
Karin
Michael
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002232:Carbocyanines; D002452:Cell Count; D002467:Cell Nucleus; D002470:Cell Survival; D020287:In Situ Nick-End Labeling; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D008817:Mice, Mutant Strains; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009900:Optic Nerve / Q000378:metabolism; D020221:Optic Nerve Injuries / Q000378:metabolism*; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism*
C035005:3,3'-dihexadecylindocarbocyanine; D002232:Carbocyanines; D016755:Proto-Oncogene Proteins c-jun; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases