TAT-mGluR1 Attenuation of Neuronal Apoptosis through Prevention of MGluR1α Truncation after Experimental Subarachnoid Hemorrhage.
ACS Chem Neurosci
; 10(1): 746-756, 2019 01 16.
Article
en En
| MEDLINE
| ID: mdl-30339347
ABSTRACT
Excessive glutamate-mediated overactivation of metabotropic glutamate receptor 1 (mGluR1) plays a leading role in neuronal apoptosis following subarachnoid hemorrhage (SAH). TAT-mGluR1, a fusion peptide consisting of a peptide spanning the calpain cleavage site of mGluR1α and the trans-activating regulatory protein (TAT) of HIV, effectively blocks mGluR1α truncation and protects neurons against excitotoxic damage. This study investigated the effects of TAT-mGluR1 on neuronal apoptosis in the rat SAH model. Here, we report that SAH caused activation of calpain and truncation of mGluR1α; intraperitoneally administered TAT-mGluR1 did not affect calpain activity, while it blocked truncation of mGluR1α after SAH. Intraperitoneally administered FITC-labeled TAT-mGluR1 was colocalized with mGluR1α in thecortex after SAH. Furthermore, TAT-mGluR1 significantly improved the neurological deficit, increased p-PI3K, p-Akt, and p-GSK3ß, downregulated Bax, upregulated Bcl-2, and reduced cortical apoptosis in the basal cortex at 24 h after SAH. These findings indicated that TAT-mGluR1 acted against SAH-induced cell apoptosis through preventing mGluR1α truncation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
1_ASSA2030
/
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
1_doencas_nao_transmissiveis
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6_cardiovascular_diseases
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6_cerebrovascular_disease
Asunto principal:
Hemorragia Subaracnoidea
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Receptores de Glutamato Metabotrópico
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Fármacos Neuroprotectores
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
ACS Chem Neurosci
Año:
2019
Tipo del documento:
Article