Age-associated differences in activation of Akt/GSK-3beta signaling pathways and inhibition of mitochondrial permeability transition pore opening in the rat heart.
J Gerontol A Biol Sci Med Sci
; 65(6): 611-9, 2010 Jun.
Article
en En
| MEDLINE
| ID: mdl-20427381
ABSTRACT
Pretreatment with isoflurane decreased myocardial infarction size in young rats (3-5 months) but not in old rats (20-24 months). To understand the mechanisms underlying the failure to protect the old myocardium, differences in phosphorylation of Akt/GSK-3beta and age-associated differences in mitochondrial permeability transition pore (mPTP) opening in the aging heart in vivo were measured. Isoflurane significantly increased Akt and GSK-3beta phosphorylation in the young groups. In contrast, levels of p-Akt and p-GSK-3beta were highly elevated in the old sham control groups. Isoflurane preconditioning significantly reduced the fall in NAD(+) levels induced by ischemia/reperfusion injury in the young animals, reflecting the inhibition of mPTP opening. In the old animals, however, isoflurane failed to prevent the fall in NAD(+) levels induced by ischemia/reperfusion injury. Lack of isoflurane-induced cardioprotective effects, seen in the old animals, can be explained by age-related differences in Akt/GSK-3beta signaling pathway and the inability to reduce mPTP opening following ischemia/reperfusion injury.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Envejecimiento
/
Transducción de Señal
/
Glucógeno Sintasa Quinasa 3
/
Proteínas de Transporte de Membrana Mitocondrial
/
Proteínas Proto-Oncogénicas c-akt
/
Miocardio
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
J Gerontol A Biol Sci Med Sci
Asunto de la revista:
GERIATRIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos