title: Novel sulfoglycolipid IG20 causes neuroprotection by activating the phase II antioxidant response in rat hippocampal slices.
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.
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Punzón
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain; Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain.
authors.forename: Fernanda
authors.initials: F
authors.lastname: García-Alvarado
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain; Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Maroto
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain; Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernández-Mendívil
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain; Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Michalska
authors.affiliation: Hospital Nacional de Parapléjicos, SESCAM, Finca La Peraleda s/n, 45071 Toledo, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: García-Álvarez
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain.
authors.forename: Juan Alberto
authors.initials: JA
authors.lastname: Arranz-Tagarro
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain; Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain.
authors.forename: Izaskun
authors.initials: I
authors.lastname: Buendia
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain; Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain.
authors.forename: Manuela G
authors.initials: MG
authors.lastname: López
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain; Servicio de Farmacología Clínica, Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, c/ Diego de León, 62, 28006 Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: León
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain; Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Gandía
authors.affiliation: Instituto de Química Orgánica General, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Fernández-Mayoralas
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain; Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain; Servicio de Farmacología Clínica, Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, c/ Diego de León, 62, 28006 Madrid, Spain. Electronic address: agg@uam.es.
authors.forename: Antonio G
authors.initials: AG
authors.lastname: García
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005947:Glucose / Q000172:deficiency; D018698:Glutamic Acid / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D006017:Glycolipids / Q000737:chemistry / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D046509:Tissue Culture Techniques; D014701:Veratridine / Q000633:toxicity
chemical_list: D000975:Antioxidants; D006017:Glycolipids; C000609953:IG20 compound; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; D014701:Veratridine; D000255:Adenosine Triphosphate; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D005978:Glutathione; D005947:Glucose
keywords: Hippocampal neurons; Hippocampal slices; Neuronal excitability; Neuroprotection; Neurotoxicity; Oxidative stress; Sulfoglycolipid IG20