G protein-coupled estrogen receptor is involved in the neuroprotective effect of IGF-1 against MPTP/MPP-induced dopaminergic neuronal injury.

G protein-coupled estrogen receptor is involved in the neuroprotective effect of IGF-1 against MPTP/MPP-induced dopaminergic neuronal injury.

Publication date: Jun 05, 2019

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 17β-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.

Yuan, L.J., Wang, X.W., Wang, H.T., Zhang, M., Sun, J.W., and Chen, W.F. G protein-coupled estrogen receptor is involved in the neuroprotective effect of IGF-1 against MPTP/MPP-induced dopaminergic neuronal injury. 21099. 2019 J Steroid Biochem Mol Biol.

Concepts Keywords
Antagonist Dopaminergic neuronal injury
Apoptotic Branches of biology
Bax Cell signaling
Brain Cell biology
Dopaminergic Growth factors
Endogenous Peptide hormones
Estradiol Intracellular receptors
Estrogen Receptor Transcription factors
G Protein Endocrinology
Growth Factor Insulin-like growth factor
Insulin GPER
Kinase Neuroprotection
MAPK MPTP
Membrane Potential
Mice
Mitochondria
Mitogen
MPP
MPTP
Neurogenesis
Neurons
Neuroprotection
Neuroprotective
Neurotoxicity
Peptide
Phosphatidylinositol
Protein
Receptor
Striatum
Substantia Nigra

Semantics

Type Source Name
disease DOID Parkinson disease
disease MESH Parkinson disease
disease MESH growth
drug DRUGBANK Dopamine
gene UNIPROT PI3
disease DOID neurotoxicity
gene UNIPROT RBM5
gene UNIPROT AGPAT1
gene UNIPROT BAX
gene UNIPROT BCL2
disease DOID cancer
disease MESH cancer
gene UNIPROT GPER1
gene UNIPROT IGF1
drug DRUGBANK Estradiol
gene UNIPROT MPZ
gene UNIPROT MPHOSPH6
drug DRUGBANK Mecasermin
disease MESH estrogen

Original Article

Leave a Comment

Your email address will not be published. Required fields are marked *