Increased expression of Fas (CD95/APO-1) in adult rat brain after kainate-induced seizures.
Fas (CD95/APO-1), a transmembrane glycoprotein and receptor for the Fas ligand, plays an important role in apoptosis. The present study examined whether excitotoxic cell death induces Fas expression in the adult rat brain. Although relatively light immunostaining was observed in control brain sections, significantly increased Fas immunoreactivity was seen from 4 h to 5 days after the onset of kainic acid-induced seizures. Increased expression of both Fas mRNA and protein were also evident by reverse transcription polymerase chain reaction and Western blotting, respectively. Fas induction was correlated with neuronal apoptosis as demonstrated by colocalization of Fas and terminal dT-mediated dUTP nick end-labeling (TUNEL). Cells with increased Fas-expression were also immunoreactive for tumor suppressor p53 and neuronal specific nuclear protein (NeuN). These results suggest that Fas receptor may contribute to excitotoxic neuronal death in cooperation with p53, and further implicates the Fas pathway in the pathophysiology of neurodegenerative diseases.
Tan
Z
Z
Departments of Neurology, USC Keck School of Medicine, 1333 San Pablo Street MCH 142, Los Angeles, CA 90033, USA.
Levid
J
J
Schreiber
S S
SS
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012640:Seizures / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D019014:fas Receptor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D007608:Kainic Acid