title: Sphingosine-1-phosphate and its effect on glucose deprivation/glucose reload stress: from gene expression to neuronal survival.
abstract: Sphingosine kinase-1 (Sphk1-1, EC 2.7.1.91) is a regulator of pro-survival signalling, and its alterations have been observed in Alzheimer's disease, brain ischemia and other neurological disorders. In this study we addressed the question whether Sphk1 and its product, sphingosine-1-phosphate (S1P), play a significant role in glucose deprivation (GD)/glucose reload (GR) stress in hippocampal neuronal cells (HT22). It was found that GD (6 h) followed by 24 h of GR evoked enhancement of the free radical level and neuronal HT22 cell death. Moreover, the significantly stronger gene expression for the pro-apoptotic Bax protein and down-regulation of the anti-apoptotic Bcl-2 and Bcl-XL proteins were observed. Concomitantly, this stress up-regulated: gene expression, protein level and activity of Sphk1. Exogenous S1P at 1 μM concentration and the other agonists of the S1P1 receptor (SEW 2871 and P-FTY720) enhanced HT22 cell viability affected by GD/GR stress. This mechanism is mediated by S1P receptor(s) signalling and by the activation of gene expression for Bcl-2 and Bcl-XL. Summarising, our data suggest that sphingolipid metabolism may play an important role in the early events that take place in neuronal cell survival/death under GD/GR stress. Our data demonstrate that exogenous S1P, through the activation of specific receptors S1P1 and S1P3 signalling pathways, regulates the gene expression for anti-apoptotic proteins and enhances neuronal cell survival affected by GD/GR stress.
authors: Laboratory of Preclinical Research and Environmental Agents, Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego Street, 02-106, Warsaw, Poland.
authors: Kinga
authors: K
authors: Czubowicz
authors: Magdalena
authors: M
authors: Cieślik
authors: Joanna
authors: J
authors: Pyszko
authors: Joanna B
authors: JB
authors: Strosznajder
authors: Robert P
authors: RP
authors: Strosznajder
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D010755:Organophosphates / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013312:Stress, Physiological
chemical_list: D051017:Apoptosis Regulatory Proteins; C525008:FTY 720P; D008246:Lysophospholipids; D010755:Organophosphates; C060506:sphingosine 1-phosphate; D005947:Glucose; D013110:Sphingosine