ERKs and mitochondria-related pathways are essential for glycyrrhizic acid-mediated neuroprotection against glutamate-induced toxicity in differentiated PC12 cells
Rev. bras. pesqui. méd. biol
; Braz. j. med. biol. res;47(9): 773-779, 09/2014. graf
Article
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| ID: lil-719311
Biblioteca responsable:
BR1.1
ABSTRACT
The present study focuses on the neuroprotective effect of glycyrrhizic acid (GA, a major compound separated from Glycyrrhiza Radix, which is a crude Chinese traditional drug) against glutamate-induced cytotoxicity in differentiated PC12 (DPC12) cells. The results showed that GA treatment improved cell viability and ameliorated abnormal glutamate-induced alterations in mitochondria in DPC12 cells. GA reversed glutamate-suppressed B-cell lymphoma 2 levels, inhibited glutamate-enhanced expressions of Bax and cleaved caspase 3, and reduced cytochrome C (Cyto C) release. Exposure to glutamate strongly inhibited phosphorylation of AKT (protein kinase B) and extracellular signal-regulated kinases (ERKs); however, GA pretreatment enhanced activation of ERKs but not AKT. The presence of PD98059 (a mitogen-activated protein/extracellular signal-regulated kinase kinase [MEK] inhibitor) but not LY294002 (a phosphoinositide 3-kinase [PI3K] inhibitor) diminished the potency of GA for improving viability of glutamate-exposed DPC12 cells. These results indicated that ERKs and mitochondria-related pathways are essential for the neuroprotective effect of GA against glutamate-induced toxicity in DPC12 cells. The present study provides experimental evidence supporting GA as a potential therapeutic agent for use in the treatment of neurodegenerative diseases.
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Texto completo:
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Bases de datos:
LILACS
Métodos Terapéuticos y Terapias MTCI:
Plantas_medicinales
Asunto principal:
Transducción de Señal
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Fármacos Neuroprotectores
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Ácido Glutámico
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Ácido Glicirrínico
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Antiinflamatorios
Idioma:
En
Revista:
Braz J Med Biol Res
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Braz. j. med. biol. res
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Braz. j. med. biol. res. (Online)
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Brazilian journal of medical and biological research
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Brazilian journal of medical and biological research (Impresso)
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Rev. bras. pesqui. méd. biol
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Revista brasileira de pesquisas médicas e biológicas
Año:
2014
Tipo del documento:
Article
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Project document
País de afiliación:
China