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Published on: September 3, 2010
Fas (CD95) may mediate delayed cell death in hippocampal CA1 sector after global cerebral ischemia
K Jin1, S H Graham, X Mao
1Buck Institute for Age Research, Novato, California 94945, USA.
Abstract:
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.
Insights
Global cerebral ischemia triggers Fas-mediated death signaling in hippocampal CA1 neurons. This pathway involves Fas, Fas-ligand, FADD, and caspase-10, contributing to delayed neuronal death after ischemic events.
Area of Science:
- Neuroscience
- Cell Biology
- Ischemia Research
Background:
- Delayed neuronal death in the hippocampus (CA1) after global cerebral ischemia involves cell death-regulatory genes.
- Mechanisms triggering the expression of these genes, such as caspases and bcl-2 family genes, remain unclear.
Purpose of the Study:
- To investigate the molecular mechanisms underlying delayed neuronal death in the CA1 sector of the hippocampus following global cerebral ischemia.
- To explore the role of the Fas-mediated death signaling pathway in this process.
Main Methods:
- Analysis of messenger ribonucleic acid (mRNA) and protein expression of Fas, Fas-ligand, FADD, caspase-10, and caspase-3 in hippocampal CA1 neurons.
- Immunoprecipitation and co-localization studies to assess protein interactions.
Main Results:
- Fas and Fas-ligand mRNA and protein were induced in vulnerable CA1 neurons 24 and 72 hours post-ischemia.
- Fas-associating protein with a novel death domain (FADD) was upregulated and interacted with Fas.
- Caspase-10 activation increased with ischemia duration and co-localized with FADD and caspase-3.
Conclusions:
- Fas-mediated death signaling is implicated in hippocampal neuronal death in the CA1 sector after global cerebral ischemia.
- The findings highlight a potential pathway involving Fas, FADD, and caspase-10 in ischemic neuronal injury.
