title: Exogenous sphingosine 1-phosphate protects murine splenocytes against hypoxia-induced injury.
abstract: Sphingosine-1-phosphate (S1P), a biologically active pleiotropic lipid, is involved in several physiological processes especially in the area of vascular biology and immunology encompassing cell survival, angiogenesis, vascular tone, immune response etc. by interacting with specific cell surface receptors. Hypoxia, a condition common to innumerable pathologies, is known to lethally affect cell survival by throwing off balance global gene expression, redox homeostasis, bioenergetics etc. Several molecular events of cellular adaptations to hypoxia have been closely linked to stabilization of hypoxia inducible factor-1α (HIF-1α). Signalling functions of S1P in physiological events central to hypoxia-induced pathologies led us to investigate efficacy of exogenous S1P in preconditioning murine splenocytes to sustain during cellular stress associated with sub-optimal oxygen. The present study recapitulated the pro-survival benefits of exogenous S1P under normobaric hypoxia. Results indicate a direct effect of S1P supplementation on boosting cellular adaptive responses via HIF-1α stabilization and, activation of pro-survival mediators ERK and Akt. Overwhelming anti-oxidative and anti-inflammatory benefits of S1P preconditioning could also be captured in the present study, as indicated by improved redox homeostasis, reduced oxidative damage, balanced anti/pro-inflammatory cytokine profiles and temporal regulation of nitric oxide secretion and intra-cellular calcium release. Hypoxia induced cell death and the associated stress in cellular milieu in terms of oxidative damage and inflammation could be alleviated with exogenous S1P preconditioning.
authors.affiliation: Experimental Biology Division, Defence Institute of Physiology and Allied Sciences (DIPAS), Ministry of Defence, Defence Research and Development Organisation (DRDO), Lucknow Road, Timarpur, Delhi, 110054, India.
authors.forename: Sonam
authors.initials: S
authors.lastname: Chawla
authors.forename: Chayanika
authors.initials: C
authors.lastname: Sahni
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Tulsawani
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Singh
authors.forename: Deepika
authors.initials: D
authors.lastname: Saraswat
authors.forename: Anju
authors.initials: A
authors.lastname: Bansal
authors.forename: Shweta
authors.initials: S
authors.lastname: Saxena
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D000860:Hypoxia / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008246:Lysophospholipids / Q000627:therapeutic use*; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013154:Spleen / Q000166:cytology*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D051057:Proto-Oncogene Proteins c-akt; D013110:Sphingosine