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Activation of the histaminergic H3 receptor induces phosphorylation of the Akt/GSK-3 beta pathway in cultured cortical neurons and protects against neurotoxic insults
- Source :
- Mariottini, C, Scartabelli, T, Bongers, G M, Arrigucci, S, Nosi, D, Leurs, R, Chiarugi, A, Blandina, P, Pellegrini-Giampietro, D E & Beatrice Passani, M 2009, ' Activation of the histaminergic H3 receptor induces phosphorylation of the Akt/GSK-3 beta pathway in cultured cortical neurons and protects against neurotoxic insults ', Journal of Neurochemistry, vol. 110, no. 5, pp. 1469-78 . https://doi.org/10.1111/j.1471-4159.2009.06249.x, Journal of Neurochemistry, 110(5), 1469-78. Wiley-Blackwell
- Publication Year :
- 2009
-
Abstract
- Stimulation of histamine H(3) receptors (H(3)R) activates G(i/o)-proteins that inhibit adenylyl cyclase and triggers MAPK and phospholipase A(2). In a previous study, we showed that H(3)R-mediated phosphorylation of Akt at Ser473 occurs in primary cultures of rat cortical neurons, but neither the downstream targets nor the function of such activation were explored. In this report we address these questions. Western blotting experiments showed that H(3)R-mediated activation of Akt in cultured rat cortical neurons was inhibited by LY 294004 and U0126, suggesting that it depends on phosphoinositide-3-kinase and mitogen-activated protein kinase kinase. H(3)R activation phosphorylated, hence inactivated, the Akt downstream effector glycogen synthase kinase-3beta, increased the expression of the antiapoptotic protein Bcl-2 and protected cultured rat and mouse cortical neurons from neurotoxic insults in a dose-dependent manner. All these effects were inhibited by the H(3)R antagonist inverse/agonist thioperamide. Mouse cortical cells expressed H(3)R as revealed by immunostaining experiments, and stimulation of H(3)R phoshorylated Akt and decreased caspase 3 activity. Hence, we uncovered a yet unexplored action of the H(3)R that may help understand the impact of H(3)R signaling in the CNS.
- Subjects :
- Cell Survival
Biology
Biochemistry
Histamine Agonists
Rats, Sprague-Dawley
Adenylyl cyclase
Glycogen Synthase Kinase 3
Mice
Cellular and Molecular Neuroscience
chemistry.chemical_compound
SDG 3 - Good Health and Well-being
Central Nervous System Diseases
GSK-3
medicine
Animals
Receptors, Histamine H3
Phosphorylation
Protein kinase A
Protein kinase B
Cells, Cultured
Cerebral Cortex
Neurons
Thioperamide
Glycogen Synthase Kinase 3 beta
Molecular biology
Rats
Neuroprotective Agents
medicine.anatomical_structure
chemistry
Neuron
Histamine H3 receptor
Proto-Oncogene Proteins c-akt
apoptosis, Bcl-2, excitotoxicity, immepip, neuroprotection
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 00223042
- Database :
- OpenAIRE
- Journal :
- Mariottini, C, Scartabelli, T, Bongers, G M, Arrigucci, S, Nosi, D, Leurs, R, Chiarugi, A, Blandina, P, Pellegrini-Giampietro, D E & Beatrice Passani, M 2009, ' Activation of the histaminergic H3 receptor induces phosphorylation of the Akt/GSK-3 beta pathway in cultured cortical neurons and protects against neurotoxic insults ', Journal of Neurochemistry, vol. 110, no. 5, pp. 1469-78 . https://doi.org/10.1111/j.1471-4159.2009.06249.x, Journal of Neurochemistry, 110(5), 1469-78. Wiley-Blackwell
- Accession number :
- edsair.doi.dedup.....9d1a1350844d890157173ec2abcc28a1