期刊
JOURNAL OF NEUROCHEMISTRY
卷 103, 期 2, 页码 509-517出版社
WILEY
DOI: 10.1111/j.1471-4159.2007.04755.x
关键词
cerebral ischemia; glial cells; neurons; sphingolipid metabolism; sphingosine-1-phosphate
资金
- NHLBI NIH HHS [R01 HL080187-03, R01 HL070274, R01 HL070274-04, R01 HL080187-02, R01 HL052233-11, R01 HL080187-01A1, R01 HL052233-12, R01 HL052233, R01 HL070274-05, R01 HL080187] Funding Source: Medline
- NIDDK NIH HHS [R01 DK062729, R01 DK062729-05, R01 DK062729-04] Funding Source: Medline
- NINDS NIH HHS [P01 NS010828, R21 NS052195, NS049263, R01 NS049263, P01 NS010828-330036, NS052195] Funding Source: Medline
Sphingosine-1 -phosphate (S1 P) is a lipid mediator that exerts multiple cellular functions through activation of a subfamily of G-protein-coupled receptors. Although there is evidence that S1P plays a role in the developing and adult CNS, little is known about the ability of brain parenchyma to synthesize this lipid. We have therefore analyzed the brain distribution of the enzymatic activity of the S1 P synthesizing enzyme, sphingosine kinase (SPHK) [EC:2.7.1.91], as well as mRNA distribution for one of the two isoforms of this enzyme, sphingosine kinase 2. SPHK activity, measured by the conversion of [H-3]sphingosine to [H-3]S1P, is highest in cerebellum, followed by cortex and brainstem. Lowest activities were found in striatum and hippocampus. Sensitivity to 0. 1 % Triton-X suggests that this activity is accounted for by SPHK2. RT-PCR and in situ hybridization studies show that mRNA for this isoform has a distribution similar to that of SPHK activity. In vivo and in vitro ischemia increase SPHK activity and SPHK2 mRNA levels. These results indicate that SPHK2 is the predominant S1P-synthesizing isoform in normal brain parenchyma. Its heterogeneous distribution, in particular laminar distribution in cortex, suggests a neuronal localization and a possible role in cortical and cerebellar functions, in normal as well as ischemic brain.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据