G protein-coupled estrogen receptor is involved in the neuroprotective effect of IGF-1 against MPTP/MPP+-induced dopaminergic neuronal injury.
J Steroid Biochem Mol Biol
; 192: 105384, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-31175966
ABSTRACT
Insulin-like growth factor-1 (IGF-1), an endogenous peptide, exerts important role in brain development, neurogenesis and neuroprotection. There are accumulating evidence for the interaction of IGF-1 and 17ß-estradiol systems. IGF-1/IGF-1 receptor (IGF-1R) signaling has been reported to regulate G-protein estrogen receptor (GPER) expression in cancer cells. Whether GPER is involved in the neuroprotective effect of IGF-1 against MPTP/MPP+-induced dopaminergic neuronal injury remains unclear. We showed that IGF-1 could improve MPTP-induced motor deficits and ameliorate the decreased contents of DA and its metabolites in striatum as well as the loss of TH-IR neurons in the substantia nigra (SN). IGF-1 pretreatment also reversed the changes of Bcl-2 and Bax protein expressions in SN in MPTP mice. These effects were abolished by IGF-1 receptor (IGF-1R) antagonist JB-1 or GPER antagonist G15 except the inhibitory effect of G15 on Bax protein expression. Moreover, IGF-1 pretreatment enhanced cell survival against MPP+-induced neurotoxicity in SH-SY5Y cells. IGF-1 exerted anti-apoptotic effects by restoring MPP+-induced changes of Bcl-2 and Bax protein expressions as well as mitochondria membrane potential. Co-treatment with JB-1 or G15 could block these effects. Furthermore, IGF-1 regulated the protein expression of GPER through activation of phosphatidylinositol 3-kinase (PI3-K) and mitogen-activated protein kinase (MAPK) signaling pathways. Overall, we show for the first time that GPER may contribute to the neuroprotective effects of IGF-1 against MPTP/MPP+-induced dopaminergic neuronal injury.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Fator de Crescimento Insulin-Like I
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Receptores de Estrogênio
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1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina
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Receptores Acoplados a Proteínas G
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Neurônios Dopaminérgicos
/
Neuroblastoma
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
J Steroid Biochem Mol Biol
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Ano de publicação:
2019
Tipo de documento:
Article