Permanent cerebral ischemia induces sustained procaspase 9L increase not controlled by Bcl-2.
Brain Res
; 966(1): 26-39, 2003 Mar 14.
Article
en En
| MEDLINE
| ID: mdl-12646305
ABSTRACT
We have investigated how transgenic overexpression of human Bcl-2 (Hu-Bcl-2) modifies cell death proteins activation in the long-term in a model of permanent cerebral ischemia induced by middle cerebral artery occlusion. Hu-Bcl-2, cytochrome c, caspases 9 and 3 expression were examined by immunoblotting and immunohistochemistry. In wild type mice, 1 day after middle cerebral artery occlusion, cytochrome c released from the mitochondria was detected. Middle cerebral artery occlusion induces a lasting activation of caspases in WT mice from day 3 post-injury. Increased level of caspase 3 is accompanied by a decrease in procaspase 3. In contrast, middle cerebral artery occlusion induced a sustained increase of procaspase 9L and a decrease in procaspase 9S concomitant to caspase 9 production. These events were observed in the operated but not in the unoperated hemisphere. Bcl-2 overexpression blocks cytochrome c release and delays caspases activation. Consequently procaspase 3 decrease was no more observed. However, Bcl-2 overexpression did not influence the middle cerebral artery occlusion-induced changes in procaspases 9 L and S. Fourteen days after middle cerebral artery occlusion the apoptotic cascade was no longer blocked in transgenic mice. Caspases 9 and 3 were increased, procaspase 3 was decreased but procaspase 9L and procaspase 9S remained increased and decreased respectively. Hu-Bcl-2 overexpression delays the activation of the cell death molecular machinery but does not control the ischemia-induced change in procaspase 9 L and S. Procaspase 9L increase is a potentially harmful event threatening cells of a rapid destruction when anti-apoptotic treatments by Bcl-2, or caspases inhibitors, are overrun.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Corteza Cerebral
/
Isquemia Encefálica
/
Proteínas Proto-Oncogénicas c-bcl-2
/
Caspasas
/
Precursores Enzimáticos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Brain Res
Año:
2003
Tipo del documento:
Article
País de afiliación:
Suiza