Cell death after exposure to subarachnoid hemolysate correlates inversely with expression of CuZn-superoxide dismutase.
Stroke
; 31(10): 2450-9, 2000 Oct.
Article
em En
| MEDLINE
| ID: mdl-11022079
ABSTRACT
BACKGROUND AND PURPOSE:
Subarachnoid hemolysate (SAH) has been associated with oxidative brain injury, cell death, and apoptosis. We hypothesized that over-expression of CuZn-superoxide dismutase (CuZn-SOD) would protect against injury after SAH, whereas reduction of its expression would exacerbate injury.METHODS:
Saline (n=16) or hemolysate (n=50) was injected into transgenic mice overexpressing CuZn-SOD (SOD1-Tg), CuZn-SOD heterozygous knockout mutants (SOD1+/-), and wild-type littermates (Wt). Mice were killed at 24 hours. Stress gene induction was evaluated by immunocytochemistry and Western blotting for hemeoxygenase-1 and heat shock protein 70. Apoptosis was evaluated by 3'-OH nick end-labeling and DNA gel electrophoresis. Cell death was quantified through histological assessment after cresyl violet staining.RESULTS:
Histological assessment demonstrated neocortical cell death in regions adjacent to the blood injection. Overall cell death was reduced 43% in SOD1-Tg mutants (n=6) compared with Wt littermates (n=6; P<0.02). In contrast, cell death was increased >40% in SOD1+/- mutants (n=6; P<0.05). Both hemeoxygenase-1 and heat shock protein 70 were induced after SAH. Apoptosis was also present after SAH, as evidenced by 3'-OH end-labeling and DNA laddering. However, the degree of stress gene induction and apoptosis did not vary between Wt, SOD1-Tg, and SOD1+/- mice.CONCLUSIONS:
The extent of CuZn-SOD expression in the cytosol correlates with cell death after exposure to SAH in a manner separate from apoptosis. Overexpression of CuZn-SOD may potentially be an avenue for therapeutic intervention.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hemorragia Subaracnóidea
/
Superóxido Dismutase
/
Hemoglobinas
/
Hemólise
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article