Activation of mitogen activated protein kinase (MAPK) pathways after soman poisoning in rat cerebellar granule neurons.
The expression of activated p38 mitogen-activated protein kinase (MAPK) and activated MAPK transcription factors c-jun, c-myc and elk-1 were examined in rat cerebellum after soman poisoning to determine the pathogenetic mechanism of the non-specific long-term effects of nerve agents. Male Wistar rats were poisoned by intramuscular administration of soman at a dose 60 microg kg(-1) (70% LD(50)) and samples were taken 1, 7 and 14 days after poisoning, immunohistochemically stained and p-p38MAPK, p-c-jun, p-c-myc and p-elk-1 expressions were measured using image analysis. Control groups were administered with saline instead of soman. The expression of activated p38MAPK and c-myc increased 14 days after soman poisoning while c-jun and elk-1 expressions remained unchanged 1, 7 and 14 days after soman poisoning. Delayed activation of p38 MAPK and its targets might be involved in the pathogenetic mechanism of the long-term neurophysiological toxic effects of nerve agents.
Center of Advanced Studies, Faculty of Medical Health Sciences, Hradec Kralove, Czech Republic.
J
J
Pejchal
J
J
Osterreicher
J
J
Kassa
A
A
Tichý
J
J
Mokrý
D000818:Animals; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D002619:Chemical Warfare Agents / Q000506:poisoning*; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D012999:Soman / Q000506:poisoning*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D002619:Chemical Warfare Agents; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D012999:Soman; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases