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Novel sulfoglycolipid IG20 causes neuroprotection by activating the phase II antioxidant response in rat hippocampal slices.
- Source :
-
Neuropharmacology [Neuropharmacology] 2017 Apr; Vol. 116, pp. 110-121. Date of Electronic Publication: 2016 Dec 20. - Publication Year :
- 2017
-
Abstract
- Compound IG20 is a newly synthesised sulphated glycolipid that promotes neuritic outgrowth and myelinisation, at the time it causes the inhibition of glial proliferation and facilitates exocytosis in chromaffin cells. Here we have shown that IG20 at 0.3-10 μM afforded neuroprotection in rat hippocampal slices stressed with veratridine, glutamate or with oxygen plus glucose deprivation followed by reoxygenation (OGD/reox). Excess production of reactive oxygen species (ROS) elicited by glutamate or ODG/reox was prevented by IG20 that also restored the depressed tissue levels of GSH and ATP in hippocampal slices subjected to OGD/reox. Furthermore, the augmented iNOS expression produced upon OGD/reox exposure was also counteracted by IG20. Additionally, the IG20 elicited neuroprotection was prevented by the presence of inhibitors of the signalling pathways Jak2/STAT3, MEK/ERK1/2, and PI3K/Akt, consistent with the ability of the compound to increase the phosphorylation of Jak2, ERK1/2, and Akt. Thus, the activation of phase II response and the Nrf2/ARE pathway could explain the antioxidant and anti-inflammatory effects and the ensuing neuroprotective actions of IG20.<br /> (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Subjects :
- Adenosine Triphosphate metabolism
Animals
Antioxidants chemistry
Cell Hypoxia drug effects
Cell Survival drug effects
Cell Survival physiology
Cells, Cultured
Glucose deficiency
Glutamic Acid toxicity
Glutathione metabolism
Glycolipids chemistry
Hippocampus metabolism
Male
Membrane Potentials drug effects
Membrane Potentials physiology
Molecular Structure
Neuroprotective Agents chemistry
Nitric Oxide Synthase Type II metabolism
Rats, Sprague-Dawley
Reactive Oxygen Species metabolism
Tissue Culture Techniques
Veratridine toxicity
Antioxidants pharmacology
Glycolipids pharmacology
Hippocampus drug effects
Neuroprotective Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7064
- Volume :
- 116
- Database :
- MEDLINE
- Journal :
- Neuropharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 28007500
- Full Text :
- https://doi.org/10.1016/j.neuropharm.2016.12.016