Estrogen inhibits Fas-mediated apoptosis in experimental stroke

Jia Jia, Zhenjun Yang, Lihui Wang, Zichun Hua, Patricia D. Hurn, Nabil Alkayed, Yun Xu

Research output: Contribution to journalArticle

Abstract

INTRODUCTION. It is well known that 17 beta-estradiol protects against brain injury in experimental stroke, and the mechanism (s) is likely multi-factorial. However, neuronal apoptosis following stroke plays a pivotal role in the pathological processes of brain ischemia and reperfusion[1]. Increasing evidence showed that the Fas/FADD signaling pathway is integral to apoptotic cell death [2]. Recent data show that increased expression of both Fas and Fas ligand in the ischemic rat brain and that infarction and measures of apoptosis are reduced in mice with a loss-of-function mutation in Fas [3]. The aim of our experiments was to determine whether brain injury after middle cerebral occlusion (MCAO) involves Fas/FADD pathway and if estradiol acts as an anti-apoptotic agent via this pathway. METHODS. Ovariectomy in mice is performed 1-2 weeks before the experiment, and estradiol is replaced by implanting a silastic capsule containing 35 ul of 180 ug/ml 17 beta-estradiol (E2, 7 days), as previously described [4]. MCAO was produced using the intraluminal suture technique [5]. Ischemic or contralateral cortex was collected at 3, 6 or 12 hr post-MCAO and analyzed for Fas and FADD mRNA and protein expression using RT-PCR and Western blot, and activation of caspases-8 and caspase-3 was determined fluorometrically. Primary cultured cortical neurons were pretreated with 17 beta-estradiol [6] in the presence and absence of monoclonal anti-Fas antibody for 48 hrs, and apoptotic cells were quantified using fluorescence activated cell sorting (FACS). RESULTS. Fas and FADD mRNA and protein were elevated in ischemic cortex relative to contralateral cortex at 3, 6 and 12 hours post-MCAO (p

Original languageEnglish (US)
JournalJournal of Cerebral Blood Flow and Metabolism
Volume27
Issue numberSUPPL. 1
StatePublished - Nov 13 2007

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Estradiol
Estrogens
Stroke
Apoptosis
anti-Fas monoclonal antibody
Brain Injuries
Brain Infarction
Suture Techniques
Messenger RNA
Fas Ligand Protein
Caspase 8
Ovariectomy
Pathologic Processes
Brain Ischemia
Caspase 3
Reperfusion
Capsules
Flow Cytometry
Proteins
Cell Death

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

Jia, J., Yang, Z., Wang, L., Hua, Z., Hurn, P. D., Alkayed, N., & Xu, Y. (2007). Estrogen inhibits Fas-mediated apoptosis in experimental stroke. Journal of Cerebral Blood Flow and Metabolism, 27(SUPPL. 1).

Estrogen inhibits Fas-mediated apoptosis in experimental stroke. / Jia, Jia; Yang, Zhenjun; Wang, Lihui; Hua, Zichun; Hurn, Patricia D.; Alkayed, Nabil; Xu, Yun.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 27, No. SUPPL. 1, 13.11.2007.

Research output: Contribution to journalArticle

Jia, J, Yang, Z, Wang, L, Hua, Z, Hurn, PD, Alkayed, N & Xu, Y 2007, 'Estrogen inhibits Fas-mediated apoptosis in experimental stroke', Journal of Cerebral Blood Flow and Metabolism, vol. 27, no. SUPPL. 1.
Jia, Jia ; Yang, Zhenjun ; Wang, Lihui ; Hua, Zichun ; Hurn, Patricia D. ; Alkayed, Nabil ; Xu, Yun. / Estrogen inhibits Fas-mediated apoptosis in experimental stroke. In: Journal of Cerebral Blood Flow and Metabolism. 2007 ; Vol. 27, No. SUPPL. 1.
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