RGD Reference Report - Estrogen inhibits Fas-mediated apoptosis in experimental stroke. - Rat Genome Database
Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Estrogen inhibits Fas-mediated apoptosis in experimental stroke.

Authors: Jia, J  Guan, D  Zhu, W  Alkayed, NJ  Wang, MM  Hua, Z  Xu, Y 
Citation: Jia J, etal., Exp Neurol. 2009 Jan;215(1):48-52. doi: 10.1016/j.expneurol.2008.09.015. Epub 2008 Oct 7.
RGD ID: 11341807
Pubmed: (View Article at PubMed) PMID:18950622
DOI: Full-text: DOI:10.1016/j.expneurol.2008.09.015

Estrogen is protective in experimental cerebral ischemia, yet the mechanism remains unclear. Fas-mediated apoptosis has been shown to be induced after cerebral ischemia and significantly contribute to ischemic brain damage. In this study, we tested if estrogen is protective against cerebral ischemia by suppressing Fas-mediated apoptosis. 17Beta-estradiol-treated and untreated ovariectomized (OVX) female mice were subjected to 2 h middle cerebral artery occlusion (MCAO). Expression of Fas and Fas-associated death domain (FADD) were measured at 3, 6 and 12 h of reperfusion by RT-PCR and Western blot, respectively. Post-ischemic activities of caspase-8 and -3 activities, the two downstream effectors of Fas-induced apoptosis, were also assayed at same time points by ELISA. Finally, Fas antibody-induced cell death in primary cortical neurons was assayed by fluorescence activated cell sorter (FACS) in the presence and absence of estradiol. Our data showed that estradiol-treated OVX female mice sustained smaller infarct compared to untreated OVX mice. Ischemia upregulated Fas and FADD expression, and increased caspase-8 and -3 activities in OVX female mouse cortex, which were significantly attenuated by estradiol. Estradiol also significantly inhibited Fas antibody-induced neuronal cell apoptosis. Our data suggests that inhibition of ischemia-induced Fas-mediated apoptosis is an important mechanism of neuroprotection by estrogen in cerebral ischemia.


Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Fadd  (Fas associated via death domain)

Genes (Mus musculus)
Fadd  (Fas (TNFRSF6)-associated via death domain)

Genes (Homo sapiens)
FADD  (Fas associated via death domain)

Additional Information