Activation of mitogen activated protein kinase (MAPK) pathways after soman poisoning in rat cerebellar granule neurons

J Appl Toxicol. 2008 Jul;28(5):689-93. doi: 10.1002/jat.1323.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebellum / cytology*
  • Cerebellum / drug effects
  • Cerebellum / enzymology*
  • Chemical Warfare Agents / poisoning*
  • Cytoplasmic Granules / drug effects
  • Cytoplasmic Granules / enzymology
  • Enzyme Activation / drug effects
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Male
  • Mitogen-Activated Protein Kinases / metabolism*
  • Neurons / drug effects
  • Neurons / enzymology*
  • Proto-Oncogene Proteins c-jun / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects*
  • Soman / poisoning*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Chemical Warfare Agents
  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogene Proteins c-myc
  • Soman
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases