Elevated p53 and lower MDM2 expression in hippocampus from patients with intractable temporal lobe epilepsy.
Recent studies of resected hippocampus from patients with intractable temporal lobe epilepsy (TLE) have yielded biochemical evidence of signalling pathways associated with apoptosis. The tumor suppressor and transcription factor p53 regulates expression of several genes involved in apoptosis. Cellular levels of p53 are regulated in part by murine double minute 2 (MDM2) via ubiquitination and degradation through the proteasome. Presently, we compared expression of p53 and MDM2 in resected hippocampus from patients with intractable TLE to matched autopsy control samples. Western blotting detected significantly higher levels of p53 within TLE samples than controls. MDM2 levels were significantly lower in patient brain and its cleaved form was more abundant. Immunohistochemistry localized elevated p53 to a mainly nuclear distribution in neurons and glia in sections from TLE hippocampus. These data extend other findings on altered expression of genes regulating cell death and survival decisions in human intractable TLE.
Engel
Tobias
T
Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
Murphy
Brona M
BM
Schindler
Clara K
CK
Henshall
David C
DC
D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D015536:Down-Regulation / Q000502:physiology; D004351:Drug Resistance; D004833:Epilepsy, Temporal Lobe / Q000235:genetics* / Q000378:metabolism* / Q000601:surgery; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology
D051736:Proto-Oncogene Proteins c-mdm2