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Peripheral axotomy induces long-term c-Jun amino-terminal kinase-1 activation and activator protein-1 binding activity by c-Jun and junD in adult rat dorsal root ganglia In vivo.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 1998 Feb 15; Vol. 18 (4), pp. 1318-28. - Publication Year :
- 1998
-
Abstract
- One of the earliest documented molecular events after sciatic nerve injury in adult rats is the rapid, long-term upregulation of the immediate early gene transcription factor c-Jun mRNA and protein in lumbar dorsal root ganglion (DRG) neurons, suggesting that c-Jun may regulate genes that are important both in the early post-injury period and during later peripheral axonal regeneration. However, neither the mechanism through which c-Jun protein is increased nor the level of its post-injury transcriptional activity in axotomized DRGs has been characterized. To determine whether transcriptional activation of c-Jun occurs in response to nerve injury in vivo and is associated with axonal regeneration, we have assayed axotomized adult rat DRGs for evidence of jun kinase activation, c-Jun phosphorylation, and activator protein-1 (AP-1) binding. We report that sciatic nerve transection resulted in chronic activation of c-Jun amino-terminal kinase-1 (JNK) in L4/L5 DRGs concomitant with c-Jun amino-terminal phosphorylation in neurons, and lasting AP-1 binding activity, with both c-Jun and JunD participating in DNA binding complexes. The timing of JNK activation was dependent on the distance of the axotomy site from the DRGs, suggesting the requirement for a retrograde transport-mediated signal. AP-1 binding and c-Jun protein returned to basal levels in DRGs as peripheral regeneration was completed but remained elevated in the case of chronic sprouting, indicating that c-Jun may regulate target genes that are involved in axonal outgrowth.
- Subjects :
- Animals
Axons physiology
Female
Ganglia, Spinal cytology
JNK Mitogen-Activated Protein Kinases
Nerve Regeneration physiology
Neurons metabolism
Phosphorylation
Rats
Rats, Wistar
Time Factors
Axotomy
Calcium-Calmodulin-Dependent Protein Kinases physiology
Ganglia, Spinal metabolism
Mitogen-Activated Protein Kinases
Proto-Oncogene Proteins c-jun metabolism
Transcription Factor AP-1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0270-6474
- Volume :
- 18
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 9454841