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Implication of the phosphatidylinositol-3 kinase/protein kinase B signaling pathway in the neuroprotective effect of estradiol in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice.
Mol Pharmacol. 2006 Apr; 69(4):1492-8.MP

Abstract

The present experiments sought to determine the implication of estrogen receptors (ERalpha and ERbeta) and their interaction with insulin-like growth factor receptor (IGF-IR) signaling pathways in neuroprotection by estradiol against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity. C57BL/6 male mice were pretreated for 5 days with 17beta-estradiol, an estrogen receptor alpha (ERalpha) agonist, 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)tris-phenol (PPT), or an estrogen receptor beta (ERbeta) agonist, 5-androsten-3beta, 17beta-diol (Delta5-diol). On day 5, mice received MPTP (9 mg/kg) or saline injections, and estrogenic treatments were continued for 5 more days. MPTP decreased striatal dopamine, measured by high-performance liquid chromatography, to 59% of control values; 17beta-estradiol and PPT but not Delta5-diol protected against this depletion. MPTP increased IGF-IR measured by Western blot, which was prevented by PPT. The phosphorylation of protein kinase B (Akt) (at serine 473), an essential mediator of IGF-I neuroprotective actions, increased after 17beta-estradiol and tended to increase with PPT but not with Delta5-diol treatments in MPTP mice. Glycogen synthase kinase 3beta (GSK3beta) phosphorylation (at serine 9) was greatly reduced in MPTP mice; this was completely prevented by PPT, whereas 17beta-estradiol and Delta5-diol treatments were less effective. The ratio between the levels of striatal Bcl-2 and BAD proteins, two apoptotic regulators, decreased after MPTP treatment. This effect was effectively prevented only in the animals treated with PPT. In nonlesioned mice, 17beta-estradiol and PPT increased phosphorylation of striatal Akt and GSK3beta, whereas the other markers measured remained unchanged. Delta5-Diol increased GSK3beta phosphorylation less than the PPT treatment. These results suggest that a pretreatment with estradiol promoted dopamine neuron survival by activating ERalpha and increasing Akt and GSK3beta phosphorylation.

Authors+Show Affiliations

Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, CHUL, 2705 Laurier Boulevard, Quebec City, Quebec, Canada G1V 4G2.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16434614

Citation

D'Astous, Myreille, et al. "Implication of the Phosphatidylinositol-3 Kinase/protein Kinase B Signaling Pathway in the Neuroprotective Effect of Estradiol in the Striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Mice." Molecular Pharmacology, vol. 69, no. 4, 2006, pp. 1492-8.
D'Astous M, Mendez P, Morissette M, et al. Implication of the phosphatidylinositol-3 kinase/protein kinase B signaling pathway in the neuroprotective effect of estradiol in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice. Mol Pharmacol. 2006;69(4):1492-8.
D'Astous, M., Mendez, P., Morissette, M., Garcia-Segura, L. M., & Di Paolo, T. (2006). Implication of the phosphatidylinositol-3 kinase/protein kinase B signaling pathway in the neuroprotective effect of estradiol in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice. Molecular Pharmacology, 69(4), 1492-8.
D'Astous M, et al. Implication of the Phosphatidylinositol-3 Kinase/protein Kinase B Signaling Pathway in the Neuroprotective Effect of Estradiol in the Striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Mice. Mol Pharmacol. 2006;69(4):1492-8. PubMed PMID: 16434614.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Implication of the phosphatidylinositol-3 kinase/protein kinase B signaling pathway in the neuroprotective effect of estradiol in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice. AU - D'Astous,Myreille, AU - Mendez,Pablo, AU - Morissette,Marc, AU - Garcia-Segura,Luis Miguel, AU - Di Paolo,Thérèse, Y1 - 2006/01/24/ PY - 2006/1/26/pubmed PY - 2006/6/20/medline PY - 2006/1/26/entrez SP - 1492 EP - 8 JF - Molecular pharmacology JO - Mol Pharmacol VL - 69 IS - 4 N2 - The present experiments sought to determine the implication of estrogen receptors (ERalpha and ERbeta) and their interaction with insulin-like growth factor receptor (IGF-IR) signaling pathways in neuroprotection by estradiol against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity. C57BL/6 male mice were pretreated for 5 days with 17beta-estradiol, an estrogen receptor alpha (ERalpha) agonist, 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)tris-phenol (PPT), or an estrogen receptor beta (ERbeta) agonist, 5-androsten-3beta, 17beta-diol (Delta5-diol). On day 5, mice received MPTP (9 mg/kg) or saline injections, and estrogenic treatments were continued for 5 more days. MPTP decreased striatal dopamine, measured by high-performance liquid chromatography, to 59% of control values; 17beta-estradiol and PPT but not Delta5-diol protected against this depletion. MPTP increased IGF-IR measured by Western blot, which was prevented by PPT. The phosphorylation of protein kinase B (Akt) (at serine 473), an essential mediator of IGF-I neuroprotective actions, increased after 17beta-estradiol and tended to increase with PPT but not with Delta5-diol treatments in MPTP mice. Glycogen synthase kinase 3beta (GSK3beta) phosphorylation (at serine 9) was greatly reduced in MPTP mice; this was completely prevented by PPT, whereas 17beta-estradiol and Delta5-diol treatments were less effective. The ratio between the levels of striatal Bcl-2 and BAD proteins, two apoptotic regulators, decreased after MPTP treatment. This effect was effectively prevented only in the animals treated with PPT. In nonlesioned mice, 17beta-estradiol and PPT increased phosphorylation of striatal Akt and GSK3beta, whereas the other markers measured remained unchanged. Delta5-Diol increased GSK3beta phosphorylation less than the PPT treatment. These results suggest that a pretreatment with estradiol promoted dopamine neuron survival by activating ERalpha and increasing Akt and GSK3beta phosphorylation. SN - 0026-895X UR - https://www.unboundmedicine.com/medline/citation/16434614/Implication_of_the_phosphatidylinositol_3_kinase/protein_kinase_B_signaling_pathway_in_the_neuroprotective_effect_of_estradiol_in_the_striatum_of_1_methyl_4_phenyl_1236_tetrahydropyridine_mice_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=16434614 DB - PRIME DP - Unbound Medicine ER -