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PMID: 11567044 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Estrogen and Bcl-2: gene induction and effect of transgene in experimental stroke.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 21 ·No. 19 ·2001-10-01 ·Pages 7543-50

Alkayed NJ, Goto S, Sugo N, Joh HD, Klaus J, Crain BJ, Bernard O, Traystman RJ, Hurn PD

Abstract

Female rodents producing endogenous estrogens are protected from stroke damage in comparison with male counterparts. This natural protection is lost after ovariectomy or reproductive senescence. The aim of this study is to determine whether estrogen reduces early neuronal injury and cell loss after ischemia by increasing the expression of Bcl-2. Male, intact female, ovariectomized, and estrogen-repleted ovariectomized rats were subjected to middle cerebral artery occlusion, and 22 hr later the level and localization of Bcl-2 mRNA and protein were determined. The levels of post-ischemic bcl-2 mRNA and protein were increased exclusively in neurons within the peri-infarct region. Intact females and estrogen-treated castrates demonstrated increased bcl-2 mRNA and protein expression compared with males and estrogen-deficient females, accompanied by a decrease in infarct size. To test the hypothesis that the neuroprotective mechanism of estrogen functions via Bcl-2, we compared ischemic outcome in male, female, and ovariectomized wild-type mice and mice overexpressing Bcl-2 exclusively in neurons. Wild-type female mice sustained smaller infarcts compared with males. Bcl-2 overexpression reduced infarct size in males, but provided no added protection in the female. Moreover, ovariectomy exacerbated infarction in wild-type females, but had no effect in Bcl-2 overexpressors. These data indicate that overexpression of Bcl-2 simulates the protection against ischemic injury conferred by endogenous female sex steroids. We concluded that estrogen rescues neurons after focal cerebral ischemia by increasing the level of Bcl-2 in peri-infarct regions and that estrogen-induced bcl-2 gene expression is an important downstream component of neuronal protection in female stroke.

MeSH Terms
Animals Cell Death/drug effects Cerebral Infarction/metabolism,pathology,prevention & control Disease Susceptibility Estrogen Replacement Therapy Estrogens/metabolism,pharmacology Female Gene Expression Gene Expression Regulation/drug effects In Situ Hybridization Male Mice Mice, Inbred C57BL Mice, Transgenic Neurons/metabolism,pathology Ovariectomy Proto-Oncogene Proteins c-bcl-2/genetics,metabolism RNA, Messenger/metabolism Rats Rats, Wistar Sex Factors Stroke/genetics,metabolism,pathology Transcriptional Activation Transgenes
Chemicals
Estrogens Proto-Oncogene Proteins c-bcl-2 RNA, Messenger
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Alkayed N J
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. [email protected]
Goto S
Sugo N
Joh H D
Klaus J
Crain B J
Bernard O
Traystman R J
Hurn P D
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Email
[email protected]
Published
2001-10-01
Pages
7543-50
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6762919
Subset
IM
Grants
NINDS NIH HHS · NS20020 · United States
NINDS NIH HHS · NS33668 · United States
External Links
PubMed source PMC Full Text View journal details
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