MAP kinase phosphatase 1 is expressed and enhanced by FK506 in surviving mamillary, but not degenerating nigral neurons following axotomy.
The MAP kinase phosphatase 1 (MKP-1), a dual serine-threonine phosphatase, inactivates the MAP kinases ERK and JNK/SAPK which are involved in neuronal survival and neuronal cell death following injury and degenerative stimuli. We have studied by immunocytochemistry whether regulation of MKP-1 is part of the cell-body response following nerve fiber transection. The expression of MKP-1 was investigated in axotomized neurons of the corpus mamillaris (CMm) and substantia nigra pars compacta (SNC) following transection of the mamillo-thalamic tract (MT) and the medial forebrain bundle (MFB), respectively. In contrast to the surviving CMm neurons, the vast majority of SNC neurons undergoes cell death following axotomy. MKP-1 immunoreactivity which is absent in untreated adult rats, appeared in CMm neurons 24 h following MT transection, reached a maximum after 2 days and persisted in a substantial proportion of CMm neurons until 20 days, the end of observation period. In contradistinction, MKP-1 could not be detected in the SNC neurons. MKP-1 immunoreactivity was virtually restricted to the nuclei of neurons. Subcutaneous injection of the immunosuppressant FK506 that protects axotomized SNC neurons against neuronal cell death, enhanced the expression of MKP-1 in CMm, but failed to do so in SNC neurons. The selective expression of MKP-1 in CMm is the first finding on a different regulation of components in the stress kinase signal pathway in surviving vs. degenerating axotomized neurons.
Winter
C
C
II. Institute of Physiology, University of Heidelberg, Im Neuenheimer Feld 326, Heidelberg 69120, Germany.
Schenkel
J
J
Zimmermann
M
M
Herdegen
T
T
D000818:Animals; D019771:Axotomy; D048588:Benzoxazines; D018797:Cell Cycle Proteins; D002470:Cell Survival / Q000187:drug effects; D054638:Dual Specificity Phosphatase 1; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000378:metabolism; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D008297:Male; D008326:Mammillary Bodies / Q000187:drug effects / Q000201:enzymology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D010078:Oxazines / Q000737:chemistry; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology*; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D048588:Benzoxazines; D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D010078:Oxazines; C028911:cresyl violet; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases; D016559:Tacrolimus