CROSS TALK BETWEEN THE SPHINGOLIPID AND FOLATE PATHWAYS
CROSS TALK BETWEEN THE SPHINGOLIPID AND FOLATE PATHWAYS
批准号:
7959970
负责人:
Natalia Ivanovna Krupenko
金额:
$14.6万
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-07-01 至 2010-06-30
关键词:
AnabolismCarbonCenters of Research ExcellenceCeramidesComputer Retrieval of Information on Scientific Projects DatabaseEnzymesFolateFolic Acid AntagonistsFolic Acid DeficiencyFundingGrantHistonesInstitutionLecithinMediationMethylationMolecularPathway interactionsPhosphatidylethanolamineProcessRegulationResearchResearch PersonnelResourcesRoleScienceSerineSignal TransductionSourceSphingolipidsStreamStressTestingUnited States National Institutes of Healthdihydroceramide desaturasefolic acid metabolisminhibitor/antagonistphosphatidylethanolamineresearch studyresponse
中文摘要
这个子项目是众多研究子项目之一
英文摘要
This subproject is one of many research subprojects utilizing the
resources provided by a Center grant funded by NIH/NCRR. The subproject and
investigator (PI) may have received primary funding from another NIH source,
and thus could be represented in other CRISP entries. The institution listed is
for the Center, which is not necessarily the institution for the investigator.
The main objective of this project is to establish the functional connection between folate and sphingolipid pathways and to explore underlying molecular mechanisms. Specifically, we propose to evaluate the role of sphingolipid signaling in mediation of the effects of folate deficiency and the disturbance of intracellular folate metabolism. The modern biomedical science lacks the studies, which would investigate functional interactions between the folate and sphingolipid pathways. There are specific indications that the two pathways are functionally connected. (1) They both rely on serine: as the principal one-carbon group donor into the folate pool and a substrate for de novo sphingolipid biosynthesis; (2) sphingolipid pathways depend on methylation, directly (methylation of phosphatidylethanolamine to phosphatidylcholine) and indirectly (regulation of enzyme expression via DNA/histones methylation), while folates are crucial for cellular methylation; (3) cross-talk between the two pathway is suggested by experiments with fumonisine, an inhibitor of ceramide synthase, and antifolates; (4) our studies have demonstrated significant changes in the levels of ceramides upon alterations of intracellular folate metabolism. Therefore, we have hypothesized that activation of sphingolipid pathways is the down-stream effect of the folate stress. The alteration of methylation in sphingolipid pathways is proposed as the underlying mechanism in this process. Aims to test the hypotheses are: Aim 1. Determine effects of folate deficiency on sphingolipid pathways. Aim 2. Explore the role of folate-dependent methylation in sphingolipid pathways. Aim 3. To determine whether ceramide signaling is a component of cellular response to impaired folate metabolism.
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Ceramide signaling in the regulation of cellular response to folate stress
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批准号:9250722
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项目类别:
-
资助金额:$34.77万
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财政年份:2015
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负责人:Natalia Ivanovna Krupenko
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依托单位:
CROSS TALK BETWEEN THE SPHINGOLIPID AND FOLATE PATHWAYS
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批准号:8360382
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项目类别:
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资助金额:$10.84万
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财政年份:2011
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负责人:Natalia Ivanovna Krupenko
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依托单位:
Nuclear function of Glycine N-methyltransferase
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批准号:8098894
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项目类别:
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资助金额:$18.25万
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财政年份:2010
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负责人:Natalia Ivanovna Krupenko
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依托单位:
Nuclear function of Glycine N-methyltransferase
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批准号:7990236
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项目类别:
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资助金额:$22.13万
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财政年份:2010
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负责人:Natalia Ivanovna Krupenko
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依托单位:
CROSS TALK BETWEEN THE SPHINGOLIPID AND FOLATE PATHWAYS
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批准号:8168048
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项目类别:
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资助金额:$10.95万
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财政年份:2010
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负责人:Natalia Ivanovna Krupenko
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依托单位:
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