Seizure-induced neuronal death is associated with induction of c-Jun N-terminal kinase and is dependent on genetic background.
Previous studies have shown that expression of c-Jun protein, as well as the c-Jun amino-terminal kinase (JNK) group of mitogen-activated protein kinases, may play a critical role in the pathogenesis of glutamate neurotoxicity. In order to define the molecular cascade that leads to c-Jun activation following excitotoxic injury and delineate whether induction of protein synthesis is related to cell death signaling cascades or those changes associated with increased seizure activity, we examined the expression of JNK-1, as well as its substrate, c-Jun and N-terminal phosphorylated c-Jun following kainic acid (KA) administration in two strains of mice. In the present study, we assessed the immunohistochemical expression of these proteins at time points between 2 h and 7 days, in excitotoxic cell death-resistant (C57BL/6) and -susceptible (FVB/N) mouse strains that were systemically injected with saline or kainic acid. No strain-related differences in the immunohistochemical expression of any of the proteins were observed in intact control mice. However, following KA administration, the magnitude and period of induction of JNK-1 protein was associated with impending cell death, while increased phosphorylation of c-Jun protein was associated with resistance to cell death. In contrast, expression of c-Jun protein does not appear to be a reliable indicator of impending cell death, as it was expressed in resistant and vulnerable subfields in mice susceptible to kainate injury. These results provide the first evidence that JNK-1 expression may be involved in producing the neuronal cell death response following excitotoxin-induced injury.
Schauwecker
P E
PE
Department of Cell and Neurobiology, University of Southern California, Keck School of Medicine, BMT 401, 1333 San Pablo Street, Los Angeles, CA 90033, USA. schauwec@hsc.usc.edu
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases; D007608:Kainic Acid / Q000009:adverse effects; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
D009498:Neurotoxins; D016755:Proto-Oncogene Proteins c-jun; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D007608:Kainic Acid