Fas (CD95) may mediate delayed cell death in hippocampal CA1 sector after global cerebral ischemia.
Cell death-regulatory genes like caspases and bcl-2 family genes are involved in delayed cell death in the CA1 sector of hippocampus after global cerebral ischemia, but little is known about the mechanisms that trigger their expression. The authors found that expression of Fas and Fas-ligand messenger ribonucleic acid and protein was induced in vulnerable CA1 neurons at 24 and 72 hours after global ischemia. Fas-associating protein with a novel death domain (FADD) also was upregulated and immunoprecipitated and co-localized with Fas. Caspase-10 was activated and interacted with FADD protein to an increasing extent as the duration of ischemia increased. Moreover, caspase-10 co-localized with both FADD and caspase-3. These findings suggest that Fas-mediated death signaling may play an important role in signaling hippocampal neuronal death in CA1 after global cerebral ischemia.
Jin
K
K
Buck Institute for Age Research, Novato, California 94945, USA.
Graham
S H
SH
Mao
X
X
Nagayama
T
T
Simon
R P
RP
Greenberg
D A
DA
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D053455:Caspase 10; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C505535:Fadd protein, rat; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D019014:fas Receptor; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; C506435:Casp9 protein, rat; D053455:Caspase 10; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases