title: Early c-Jun N-terminal kinase-dependent phosphorylation of activating transcription factor-2 is associated with degeneration of retinal ganglion cells.
abstract: Neuron death due to deprivation of target-derived neurotrophic factors depends on protein synthesis regulated by transcription factor activity. We investigated the content and phosphorylation of activating transcription factor 2 (ATF-2) in axon-damaged retinal ganglion cells of neonatal rats. In the retina of neonatal rats, the ATF-2 protein is predominantly located in the nucleus of the ganglion cells. A gradual loss of the immunoreactivity for ATF-2 occurred after explantation. ATF-2 is phosphorylated early after explantation, with a peak within 3 hours, preceding the peak of cell death that occurs at 18 hours. Both the phosphorylation of ATF-2 and ganglion cell death were blocked by treatment with an inhibitor of c-Jun N-terminal kinase (JNK), whereas an inhibitor of p38 reduced only slightly the rate of ganglion cell death with no effect upon phosphorylation of ATF-2. Inhibitors of phosphatidyl inositol 3 kinase (PI-3K), protein kinase C (PKC) or extracellular regulated kinase (ERK) had no effect. Finally, the inhibitor of JNK blocked the upregulation of both c-Jun and Hrk in the GCL after retinal explantation. The data show that phosphorylation of ATF-2 by JNK is associated with retinal ganglion cell death after axon damage.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, UFRJ, Rio de Janeiro, Brasil.
authors.forename: V T
authors.initials: VT
authors.lastname: Ribas
authors.forename: M
authors.initials: M
authors.lastname: Arruda-Carvalho
authors.forename: R
authors.initials: R
authors.lastname: Linden
authors.forename: L B
authors.initials: LB
authors.lastname: Chiarini
mesh_terms: D051698:Activating Transcription Factor 2 / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D012165:Retinal Ganglion Cells / Q000378:metabolism*
chemical_list: D051698:Activating Transcription Factor 2; C497107:Atf2 protein, rat; D048031:JNK Mitogen-Activated Protein Kinases