Topics

Tolerance induced by DHPG postconditioning is mediated by the PI3K/Akt/GSK3β signalling pathway in an in vitro model of cerebral ischemia.

07:00 EST 11th January 2020 | BioPortfolio

Summary of "Tolerance induced by DHPG postconditioning is mediated by the PI3K/Akt/GSK3β signalling pathway in an in vitro model of cerebral ischemia."

Ischemic postconditioning (PostC) is an endogenous neuroprotective strategy for cerebral ischemia induced by low activation of glutamate receptors. We have previously shown that the application of the mGluR1/5 agonist (S)-3,5-dihydroxyphenylglycine (DHPG) 5 min after 30 min of oxygen and glucose deprivation (OGD) reduces CA1 damage in organotypic hippocampal slices by activating the PI3K-Akt signalling pathway. In order to extend these data, we analysed the production of reactive oxygen species (ROS) and the glycogen synthase kinase 3β (GSK3β) signalling pathway. Our results show that DHPG PostC was associated with a reduction in the formation of ROS that is massively increased 24 h after OGD exposure. This reduction was prevented by the PI3K inhibitor LY294002, indicating that there is a link between the PI3K/Akt pathway and the formation of ROS in the protective mechanisms of PostC. DHPG PostC also induces a transient increased in GSK3β phosphorylation and inactivation that is followed by nuclear accumulation of β-catenin, that probably lead to the up-regulation of neuroprotective genes. Our results propose GSK3β as new target for neuroprotection, therefore, we verified that the two GSK3β inhibitors N-(3-Chloro-4-methylphenyl)-5-(4-ni​trophenyl)-1,3,4-oxadiazol-2-amine (TC-G 24) and LiCl are neuroprotective agents in OGD and also can be used as PostC agents.

Affiliation

Journal Details

This article was published in the following journal.

Name: Neuroscience
ISSN: 1873-7544
Pages:

Links

DeepDyve research library

PubMed Articles [16022 Associated PubMed Articles listed on BioPortfolio]

Neuroprotective effects of mGluR5 activation through the PI3K/Akt pathway and the molecular switch of AMPA receptors.

Previous studies have demonstrated that antagonists of mGluR1, but not mGluR5, are neuroprotective in models of cerebral ischemia. To investigate the individual roles of mGlu1 and mGlu5 receptors in i...

Converging TLR9 and PI3Kgamma signaling induces sterile inflammation and organ damage.

Toll-like receptor 9 (TLR9) and Phosphatidylinositol-3-kinase gamma (PI3Kγ) are very important effectors of the immune response, however, the importance of such crosstalk for disease development is s...

BMP9 directly induces rapid GSK3-β phosphorylation in a Wnt-independent manner through class I PI3K-Akt axis in osteoblasts.

Bone morphogenetic protein (BMP)9 has been reported to be the most potent BMP to induce bone formation. However, the details of BMP9-transduced intracellular signaling remain ambiguous. Here, we have ...

The role of μ-opioid receptors in respiratory distress syndrome μ-opioid receptor signalling via PI3K/Akt pathway ameliorates lipopolysaccharide-induced acute respiratory distress syndrome.

What is the central question of this study? The aim of this study was to investigate the role of μ-opioid receptors in acute respiratory distress syndrome and whether their protective effect is media...

KCa3.1 deficiency attenuates neuroinflammation by regulating an astrocyte phenotype switch involving the PI3K/AKT/GSK3β pathway.

Neuroinflammation may induce a phenotype switch to reactive astrogliosis in neurodegenerative disorders. The calcium-activated potassium channel (KCa3.1) is active in the phenotypic switch that occurs...

Clinical Trials [5953 Associated Clinical Trials listed on BioPortfolio]

A Study of the Safety and Tolerance of Long-Term Therapy With Intravenous Cytovene (Ganciclovir Sodium) for Cytomegalovirus Retinitis in Persons With AIDS

To evaluate the safety and tolerance of long-term ganciclovir (DHPG) therapy for newly diagnosed macular threatening Cytomegalovirus (CMV) retinitis in AIDS patients. To evaluate the clini...

A Phase I/II Trial to Assess the Safety and Tolerance of Escalating Doses of a Human Anti-Cytomegalovirus Monoclonal Antibody (SDZ MSL-109) in Patients With the Acquired Immunodeficiency Syndrome and CMV Retinitis

To determine the safety and tolerance of 3 dosage levels of human anti-cytomegalovirus (CMV) monoclonal antibody (SDZ MSL-109) when administered once every 2 weeks for a total of 8 doses d...

Postconditioning in Primary PCI and Direct Stenting

To determine the safety and efficacy of 2 vs 4 cycles of postconditioning method during primary PCI and direct stenting in acute MI, and to compared to primary PCI and direct stenting wit...

Remote Ischemic Postconditioning in Humans

The aim of this study is to evaluate the phenomenon of remote ischemic postconditioning in humans. The minor myocardial damage associated with percutaneous revascularization procedures may...

Positive Effect of Ischemic Postconditioning During Acute Myocardial Infarction

The purpose of this study is to determine whether brief periods of ischemia performed just at the time of reperfusion -postconditioning- can reduce coronary endothelial dysfunction and inf...

Medical and Biotech [MESH] Definitions

An induced state of non-reactivity to grafted tissue from a donor organism that would ordinarily trigger a cell-mediated or humoral immune response.

Differentiation antigens expressed on pluripotential hematopoietic cells, most human thymocytes, and a major subset of peripheral blood T-lymphocytes. They have been implicated in integrin-mediated cellular adhesion and as signalling receptors on T-cells.

An Ig domain-containing membrane receptor that is expressed by TH1 CELLS. It regulates the activation of MACROPHAGES and inhibits TH1-mediated auto- and alloimmune responses to promote IMMUNE TOLERANCE.

The normal lack of the ability to produce an immunological response to autologous (self) antigens. A breakdown of self tolerance leads to autoimmune diseases. The ability to recognize the difference between self and non-self is the prime function of the immune system.

The ability of some cells or tissues to withstand ionizing radiation without serious injury. Tolerance depends on the species, cell type, and physical and chemical variables, including RADIATION-PROTECTIVE AGENTS and RADIATION-SENSITIZING AGENTS.

Quick Search


DeepDyve research library

Searches Linking to this Article