Induction of the dual specificity phosphatase PAC1 in rat brain following seizure activity.
Recurrent seizure activity leads to delayed neuronal death as well as to inflammatory responses involving microglia in hippocampal subfields CA1, CA3 and CA4. Since mitogen activated protein (MAP) kinases control neuronal apoptosis and trigger generation of inflammatory cytokines, their activation state could determine seizure-related brain damage. PAC1 is a dual specificity protein phosphatase inactivating MAP kinases which we have found to be undetectable in normal brain. Despite this, kainic acid-induced seizure activity lead to rapid (approximately 3 h) but transient appearance of PAC1 mRNA in granule cells of the dentate gyrus as well as in pyramidal CA1 neurons. This pattern changed with time and after 2-3 days PAC1 was induced in dying CA1 and CA3 neurons. At this time PAC1 mRNA was also expressed in white matter microglia as well as in microglia invading the damaged hippocampus. PAC1 may play an important role controlling MAP kinase involvement in both neuronal death and neuro-inflammation following excitotoxic damage.
Boschert
U
U
Geneva Biomedical Research Institute, Glaxo Wellcome Research and Development SA, Switzerland.
Muda
M
M
Camps
M
M
Dickinson
R
R
Arkinstall
S
S
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000201:enzymology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D054641:Dual Specificity Phosphatase 2; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007249:Inflammation / Q000201:enzymology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D054648:Protein Phosphatase 2; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000201:enzymology*; D013379:Substrate Specificity; D048051:p38 Mitogen-Activated Protein Kinases
D009419:Nerve Tissue Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D054648:Protein Phosphatase 2; D054641:Dual Specificity Phosphatase 2; C517034:Dusp2 protein, rat; D017027:Protein Tyrosine Phosphatases