Amino-terminal phosphorylation of c-Jun regulates apoptosis in the retinal ganglion cells by optic nerve transection

K Yoshida, A Behrens, H Le-Niculescu… - … & visual science, 2002 - iovs.arvojournals.org
K Yoshida, A Behrens, H Le-Niculescu, EF Wagner, T Harada, J Imaki, S Ohno, M Karin
Investigative ophthalmology & visual science, 2002iovs.arvojournals.org
purpose. 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 …
Abstract
purpose. 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.
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