Biomarkers for the two phase switches of mammalian hibernation
哺乳动物冬眠两个阶段转换的生物标志物
基本信息
- 批准号:7586799
- 负责人:
- 金额:$ 37.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-03-15 至 2012-02-28
- 项目状态:已结题
- 来源:
- 关键词:AbbreviationsAnimalsArousalBiochemicalBiological MarkersBiologyBody TemperatureBody Weight decreasedBrainBrain StemCharacteristicsCommunitiesDevelopmentDrug Delivery SystemsEnsureEventExhibitsFatty acid glycerol estersFoundationsGelGene ExpressionGeneticGoalsGrowthHealthHeartHeart ArrestHematological DiseaseHibernationHomeostasisHumanHypothalamic structureLeadLiquid ChromatographyLiverLungMammalsMass Spectrum AnalysisMedicineMetabolicMolecularMonitorNMR SpectroscopyNamesNatureOperative Surgical ProceduresOrganOrgan TransplantationOutcomePathway interactionsPatternPhasePhenotypePhylogenetic AnalysisPlasmaProteinsProteomicsProtocols documentationReperfusion InjuryReproductionResearchResistanceResourcesSamplingScienceSeasonsSourceSpermophilusStrokeTechniquesTelemetryTestingTherapeutic InterventionTissue BankingTissue BanksTissue ExtractsTissuesTraumaWeight GainWorkanimal tissuebasedepresseddepressionfallsimprovedinsightmetabolomicsnatural hypothermianovelprotein metaboliterespiratorysuccess
项目摘要
Mammals that hibernate depress their metabolic, heart and respiratory rates, as well as their core body
temperature (Tb) to enter a state called torpor. In hibernators such as ground squirrels, torpor is precisely
controlled and fully reversible using only endogenous mechanisms, yet relatively little is known about the
molecular events that underlie hibernation's critical transitions. Understanding the biochemical aspects well
enough to recapitulate them in a non-hibernator has profound implications for human health, offering an
unprecedented opportunity to improve outcomes for victims of cardiac arrest, stroke, trauma, and
hypothermia, as well as in organ transplant and routine surgery. Hibernation is an adaptive strategy for
energy conservation that is exploited by many distantly related mammals; this broad phylogenetic distribution
argues strongly that genetic capability underlying the phenotype is shared among mammals. Thus, we predict
that an understanding of natural mammalian hibernation will lead to rational development of safe
hypometabolic and protective strategies for human applications. Here we propose that hibernation comprises
two biochemical switches: the first switch is a summer-to-winter switch that resets gene expression in a
number of pathways leading to a protected phenotype. The second switch is a torpor-to-arousal switch that
creates the heterothermic pattern characteristic to the hibernating phenotype and is responsible for reversible
metabolic suppression. Markers associated with these two switches will be identified using proteomic and
metabolomic techniques. The success of this work critically depends upon a carefully collected set of samples
based upon the natural rhythms associated with the two switches. 21 sample groups from 13-lined ground
squirrels will be analyzed, 9 for the summer-to-winter switch and 12 for the torpor-to-arousal switch. Initial
focus will be on plasma, heart, lung, liver and brain, but other tissues will be collected to make a tissue bank of
these valuable timepoints for additional studies and for use by the hibernation research community.
Identification of these markers increases understanding of mammalian hibernation, and provides significant
novel insights into natural mechanisms that achieve metabolic suppression and protection from
ischemia/reperfusion injury in mammals. These markers offer an untapped source for discovery of new targets
for therapeutic intervention in heart, lung and blood diseases in humans.
冬眠的哺乳动物会降低它们的新陈代谢、心率和呼吸频率,以及它们的核心身体
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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SANDRA L MARTIN其他文献
SANDRA L MARTIN的其他文献
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{{ truncateString('SANDRA L MARTIN', 18)}}的其他基金
Examining the hibernating brain for temperature-sensitive RNA editing
检查冬眠大脑的温度敏感 RNA 编辑
- 批准号:
8891084 - 财政年份:2015
- 资助金额:
$ 37.57万 - 项目类别:
Brown fat dynamics: elucidation of molecular drivers using hibernation as a model
棕色脂肪动力学:以冬眠为模型阐明分子驱动因素
- 批准号:
8442923 - 财政年份:2012
- 资助金额:
$ 37.57万 - 项目类别:
Brown fat dynamics: elucidation of molecular drivers using hibernation as a model
棕色脂肪动力学:以冬眠为模型阐明分子驱动因素
- 批准号:
8282994 - 财政年份:2012
- 资助金额:
$ 37.57万 - 项目类别:
Biomarkers for the two phase switches of mammalian hibernation
哺乳动物冬眠两个阶段转换的生物标志物
- 批准号:
7820965 - 财政年份:2009
- 资助金额:
$ 37.57万 - 项目类别:
Biomarkers for the two phase switches of mammalian hibernation
哺乳动物冬眠两个阶段转换的生物标志物
- 批准号:
8022882 - 财政年份:2008
- 资助金额:
$ 37.57万 - 项目类别:
Biomarkers for the two phase switches of mammalian hibernation
哺乳动物冬眠两个阶段转换的生物标志物
- 批准号:
7426147 - 财政年份:2008
- 资助金额:
$ 37.57万 - 项目类别:
Biomarkers for the two phase switches of mammalian hibernation
哺乳动物冬眠两个阶段转换的生物标志物
- 批准号:
7767006 - 财政年份:2008
- 资助金额:
$ 37.57万 - 项目类别:
GENETICS AND BIOCHEMISTRY OF A MURINE RETROPOSON
鼠逆转录子的遗传学和生物化学
- 批准号:
6385730 - 财政年份:1988
- 资助金额:
$ 37.57万 - 项目类别:
Genetics and Biochemistry of a Murine Retroposon
鼠逆转录子的遗传学和生物化学
- 批准号:
7646473 - 财政年份:1988
- 资助金额:
$ 37.57万 - 项目类别:
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