Anti-porin antibodies prevent excitotoxic and ischemic damage to brain tissue.
J Neurotrauma
; 20(7): 633-47, 2003 Jul.
Article
en En
| MEDLINE
| ID: mdl-12908925
ABSTRACT
The mitochondrial permeability transition (MPT) is a converging event for different molecular routes leading to cellular death after excitotoxic/oxidative stress, and is considered to represent the opening of a pore in the mitochondrial membrane. There is evidence that the outer mitochondrial membrane protein porin is involved in the MPT and apoptosis. We present here a proof-of-principle study to address the hypothesis that anti-porin antibodies can prevent excitotoxic/ischemia-induced cell death. We generated anti-porin antibodies and show that the F(ab)(2) fragments penetrate living cells, reduce Ca(2+)-induced mitochondrial swelling as other MPT blockers do, and decrease neuronal death in dissociated and organotypic brain slice cultures exposed to excitotoxic and ischemic episodes. These observations present direct evidence that anti-porin antibody fragments prevent cell damage in brain tissue, that porin is a crucial protein involved in mitochondrial and cell dysfunction, and that it is conceivable that antibodies can be used as therapeutic agents.
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Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_cardiovascular_diseases
/
6_cerebrovascular_disease
Asunto principal:
Isquemia Encefálica
/
Porinas
/
Agonistas de Aminoácidos Excitadores
/
Hipocampo
/
Anticuerpos
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
J Neurotrauma
Asunto de la revista:
NEUROLOGIA
/
TRAUMATOLOGIA
Año:
2003
Tipo del documento:
Article
País de afiliación:
Canadá