Novel sulfoglycolipid IG20 causes neuroprotection by activating the phase II antioxidant response in rat hippocampal slices

Los datos de investigación asociados a este artículo están disponibles en http://dx.doi.org/10.1016/j.neuropharm.2016.12.016Compound 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 IG20This study was supported by a grant from Ministerio de Economía y Competitividad, Spain (MINECO SAF2013-44108-P to AGG and LG; MAT2015-65184-C2-2-R to AFM, CABICYC UAM-Bioiberica and European Commission-ERC, People (Marie Curie Actions) FP7 under REA grant agreement n PCIG11-GA-2012-322156; Spanish Ministry of Health (Instituto de Salud Carlos III) (grant PI14/00372) and Miguel Servet (CP11/00165); Bayer A.G., “From Targets to Novel Drugs” program (grant 2015-03-1282) and Fundacion FIPSE (grant 12-00001344-15) to RL. RL thanks IS Carlos III for research contract under Miguel Servet Program. P.M. thanks MECD for FPU fellowship (AP2010-1219