Peripheral but not central axotomy induces changes in Janus kinases (JAK) and signal transducers and activators of transcription (STAT)

Nerve injury leads to the release of a number of cytokines which have been shown to play an important role in cellular activation after peripheral nerve injury. The members of the signal transducer and activator of transcription (STAT) gene family are the main mediators in the signal transduction pa...

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Bibliographic Details
Published in:The European journal of neuroscience 2000-04, Vol.12 (4), p.1165-1176
Main Authors: Schwaiger, Franz-Werner, Schmitt, Gerhard Hager andreas B., Horvat, Andrea, Hager, Gundel, Streif, Robert, Spitzer, Christoph, Gamal, Singer, Breuer, Sebastian, Brook, Gary A., Nacimiento, Wilhelm, Kreutzberg, Georg W.
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - genetics
axonal regeneration
Axotomy
Cytokine Receptor gp130
DNA Primers
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Facial Nerve - cytology
Facial Nerve - physiology
Gene Expression Regulation, Enzymologic
Hypoglossal Nerve - cytology
Hypoglossal Nerve - physiology
In Situ Hybridization
Janus Kinase 2
Janus Kinase 3
Male
Membrane Glycoproteins - genetics
Milk Proteins
Nerve Regeneration - physiology
Neurons - enzymology
Phosphorylation
Protein-Tyrosine Kinases - genetics
Protein-Tyrosine Kinases - metabolism
Proto-Oncogene Proteins
rat
Rats
Rats, Wistar
RNA, Messenger - analysis
signal transduction
Signal Transduction - physiology
spinal cord hemisection
Spinal Cord Injuries - metabolism
STAT1 Transcription Factor
STAT3 Transcription Factor
STAT5 Transcription Factor
Trans-Activators - genetics
Trans-Activators - metabolism
transcription factor
Transcriptional Activation - physiology
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Summary:Nerve injury leads to the release of a number of cytokines which have been shown to play an important role in cellular activation after peripheral nerve injury. The members of the signal transducer and activator of transcription (STAT) gene family are the main mediators in the signal transduction pathway of cytokines. After phosphorylation, STAT proteins are transported into the nucleus and exhibit transcriptional activity. Following axotomy in rat regenerating facial and hypoglossal neurons, a transient increase of mRNA for JAK2, JAK3, STAT1, STAT3 and STAT5 was detected using in situ hybridization and semi‐quantitative polymerase chain reaction (PCR). Of the investigated STAT molecules, only STAT3 protein was significantly increased. In addition, activation of STAT3 by phosphorylation on position Tyr705 and enhanced nuclear translocation was found within 3 h in neurons and after 1 day in astrocytes. Unexpectedly, STAT3 tyrosine phosphorylation was obvious for more than 3 months. In contrast, none of these changes was found in response to axotomy of non‐regenerating Clarke's nucleus neurons, although all the investigated models express c‐Jun and growth‐associated protein‐43 (GAP‐43) in response to axonal injury. Increased expression of Janus kinase (JAK) and STAT molecules after peripheral nerve transection suggests changes in the responsiveness of the neurons to signalling molecules. STAT3 as a transcription factor, which is expressed early and is activated persistently until the time of reinnervation, might be involved in the switch from the physiological gene expression to an ‘alternative program’ activated only after peripheral nerve injury.
ISSN:0953-816X
1460-9568
DOI:10.1046/j.1460-9568.2000.00005.x