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Microvascular Sphingosine Kinase Isoforms in Cerebral Hypoxic Preconditioning
Author(s) -
Wacker Bradley K,
Gidday Jeffrey M
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.733.9
Subject(s) - sphingosine , enos , protein kinase b , neuroprotection , angiogenesis , sphingosine kinase , sphingosine 1 phosphate , medicine , pharmacology , chemistry , microbiology and biotechnology , cancer research , endocrinology , biology , signal transduction , nitric oxide , nitric oxide synthase , receptor
Hypoxic preconditioning (HPC) provides robust neuroprotection against ischemia‐induced neurovascular dysfunction and cell death following stroke and may depend on augmentation of Akt and eNOS signaling pathways. Studies of preconditioning in myocardium reveal sphingosine kinase (SphK) activity could be involved. To test the hypothesis that cerebral HPC may also require SphK, we preconditioned Swiss‐Webster ND4 mice for 4 h at 8% oxygen and measured SphK1 and SphK2 expression in cortical microvessel lysates by immunoblotting. Although no change in SphK1 level was detected, SphK2 increased 2‐fold versus sham (P<0.05) 2 h post‐HPC. No change was seen prior to 2h and SphK2 returned toward baseline after 2h. The SphK2 product S1P induces Akt and eNOS phosphorylation, suggesting that SphK2 upregulation may contribute to ischemic protection promoted by HPC. SphK activity and knockdown experiments to identify the role of SphK2 in HPC signaling by Akt and eNOS are underway in a cerebral endothelial cell culture model of HPC. These studies indicate SphK2 may be important in establishing a vasculo‐protective phenotype in the cerebral microcirculation in response to HPC. Supported by NIH grant HL79278.