Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-12-20
pubmed:abstractText
Female animals are protected from ischemic brain damage relative to age-matched males, in part through protection provided by endogenous estradiol. In brain, estradiol is produced from testosterone by cytochrome P450 aromatase (cyp 19), a steroid synthetic enzyme present in astrocytes. We tested the hypothesis that astrocytes derived from neonatal female rat brain are less susceptible than male cells to oxygen-glucose deprivation (OGD), and that this endogenous protection is associated with enhanced aromatase activity. Primary cultured cortical astrocytes were prepared from male and female rat pups separately and grown to confluence in estrogen-free media. Cell death in response to OGD, alone or in combination with hydrogen peroxide, lipopolysaccharides, interleukin-1beta, tissue necrosis factor-alpha, or nitric oxide (NO) donor diethylenetriamine/nitric oxide adduct (DETA/NO) was quantified as the ratio of propidium iodide to calcein AM-positive cells. Aromatase activity and cyp19 mRNA and protein levels were measured in cultures from each sex. Female astrocytes are more resistant to OGD and oxidant cell death induced by H(2)O(2) , but sustain greater cell death when inflammatory mediators are combined with OGD compared with OGD alone. Media transfer from female to male cells conferred protection against OGD-induced cell death. Aromatase activity and expression is greater in female than in male astrocytes. The aromatase inhibitor, Arimidex (100 nmol/L), abolishes sex differences in OGD-induced cell death, whereas treatment with 17beta-estradiol (10 nmol/L) protects cells of either sex. We conclude that astrocytes isolated from neonatal cortex exhibit marked sex differences in sensitivity to OGD, in part because of enhanced aromatization and estradiol formation in female cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0271-678X
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
135-41
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:16736049-Animals, pubmed-meshheading:16736049-Aromatase, pubmed-meshheading:16736049-Astrocytes, pubmed-meshheading:16736049-Blotting, Western, pubmed-meshheading:16736049-Cell Death, pubmed-meshheading:16736049-Cell Hypoxia, pubmed-meshheading:16736049-Cells, Cultured, pubmed-meshheading:16736049-Female, pubmed-meshheading:16736049-Glucose, pubmed-meshheading:16736049-Hydrogen Peroxide, pubmed-meshheading:16736049-Interleukin-1beta, pubmed-meshheading:16736049-Lipopolysaccharides, pubmed-meshheading:16736049-Male, pubmed-meshheading:16736049-Nitric Oxide, pubmed-meshheading:16736049-Oxidative Stress, pubmed-meshheading:16736049-RNA, pubmed-meshheading:16736049-Rats, pubmed-meshheading:16736049-Rats, Sprague-Dawley, pubmed-meshheading:16736049-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16736049-Sex Characteristics, pubmed-meshheading:16736049-Tumor Necrosis Factor-alpha
pubmed:year
2007
pubmed:articleTitle
Role of P450 aromatase in sex-specific astrocytic cell death.
pubmed:affiliation
Department of Anesthesiology and Peri-Operative Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA. liumi@ohsu.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural