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

Kazuhiko Yoshida, Axcel Behrens, Helen Le-Niculescu, Erwin F. Wagner, Takayuki Harada, Junko Imaki, Shigeaki Ohno, Michael Karin

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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.

Original languageEnglish (US)
Pages (from-to)1631-1635
Number of pages5
JournalInvestigative Ophthalmology and Visual Science
Volume43
Issue number5
StatePublished - 2002
Externally publishedYes

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Optic Nerve Injuries
Retinal Ganglion Cells
Phosphorylation
Apoptosis
In Situ Nick-End Labeling
Retina
Proto-Oncogene Proteins c-jun
Superior Colliculi
Optic Nerve
Ganglia
Alanine
Serine

ASJC Scopus subject areas

  • Ophthalmology

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Amino-terminal phosphorylation of c-Jun regulates apoptosis in the retinal ganglion cells by optic nerve transection. / Yoshida, Kazuhiko; Behrens, Axcel; Le-Niculescu, Helen; Wagner, Erwin F.; Harada, Takayuki; Imaki, Junko; Ohno, Shigeaki; Karin, Michael.

In: Investigative Ophthalmology and Visual Science, Vol. 43, No. 5, 2002, p. 1631-1635.

Research output: Contribution to journalArticle

Yoshida, Kazuhiko ; Behrens, Axcel ; Le-Niculescu, Helen ; Wagner, Erwin F. ; Harada, Takayuki ; Imaki, Junko ; Ohno, Shigeaki ; Karin, Michael. / Amino-terminal phosphorylation of c-Jun regulates apoptosis in the retinal ganglion cells by optic nerve transection. In: Investigative Ophthalmology and Visual Science. 2002 ; Vol. 43, No. 5. pp. 1631-1635.
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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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T1 - Amino-terminal phosphorylation of c-Jun regulates apoptosis in the retinal ganglion cells by optic nerve transection

AU - Yoshida, Kazuhiko

AU - Behrens, Axcel

AU - Le-Niculescu, Helen

AU - Wagner, Erwin F.

AU - Harada, Takayuki

AU - Imaki, Junko

AU - Ohno, Shigeaki

AU - Karin, Michael

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N2 - 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.

AB - 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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