INFLUENCE OF AGING ON MITOCHONDRIAL GENE EXPRESSION FOLLOWING TRAUMA-HEMORRHAGE
衰老对创伤出血后线粒体基因表达的影响
基本信息
- 批准号:7470522
- 负责人:
- 金额:$ 17.84万
- 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:2008-04-01 至 2010-03-31
- 项目状态:已结题
- 来源:
- 关键词:AgeAgingAging-Related ProcessAnimalsAreaBiology of AgingCardiacCardiac MyocytesCardiovascular PhysiologyCardiovascular systemComplexConditionDataDepressed moodDevelopmentDiseaseExperimental ModelsFunctional disorderGene ChipsGene ExpressionGene Expression ProfileGenesGenomeGoalsHealthHeartHemorrhageHemorrhagic ShockHypoxiaImpairmentInterventionKnowledgeLiquid substanceMeasuresMetabolismMethodsMissionMitochondriaMitochondrial DNAModelingMolecularMusMyocardialMyocardial dysfunctionMyocardiumNuclearNumbersOligonucleotide MicroarraysOligonucleotidesOrganOutcomePersonal SatisfactionPlayRattusResearchResearch PersonnelResuscitationRodentRoleSepsisShockStandards of Weights and MeasuresStressStructureTestingTissuesTraumaWorkage relatedagedbasecostdesigngene functionheart functionhuman diseasein vitro Modelinnovationmitochondrial genomemortalityrat genomeresearch studytoolyoung adult
项目摘要
DESCRIPTION (provided by applicant): There is a fundamental gap in understanding how aging process alters mitochondrial gene expression in health and disease. It is well known that cardiovascular functions are markedly depressed following trauma-hemorrhagic shock despite fluid resuscitation. Since mitochondrial functions are also depressed under those conditions, information concerning the age related alterations in mitochondrial gene expression after shock will be useful in understanding the role of aging and mitochondrial genes in cardiac impairment and potentially devising appropriate intervention strategies. Our long-term goal is to determine the molecular basis of the age-associated alteration of cardiac mitochondrial genes following shock and trauma. Our central hypothesis is that trauma-hemorrhagic shock leads to age- specific pathological alterations in the mitochondrial gene expression in the heart, which can be determined in an experimental model using a mitochondrial gene chip. The objective of this proposal is to develop and validate a rodent mitochondrial gene chip and use it to determine the alteration in the cardiac mitochondrial gene expression in a rat model of trauma-hemorrhagic shock. This objective will be achieved by pursuing the following three specific aims: (1) develop a rodent mitochondrial gene chip, RoMITOchip, to determine age related mitochondrial gene expression changes in an experimental model of trauma-hemorrhagic shock, ( 2) validate the RoMITOchip using (i)in vitro models of rat and mouse cardiomyocytes subjected to hypoxic and normoxic conditions, (ii) mice with inherent alteration in mitochondrial function; and (3) determine the role of aging in mitochondrial gene expression profile in the normal rat and a rat model of trauma-hemorrhagic shock using RoMITOchip. The small number of genes on the mitochondrial genome is not represented in the Affymetrix rat or mouse GeneChip. The RoMITOchip, our focused array, will include genes from the nuclear genome that contribute to the mitochondrial structure and function as well as the genes on the mitochondrial DNA, together called as mitochondrial genes. We will incorporate mitochondrial genes of the rat and the mouse into the single gene chip, RoMITOchip, and plan to use this tool to determine cardiac mitochondrial gene expression changes following trauma-hemorrhage in the young adult and aged rats. Thus the proposed research is relevant to that part of NIH's mission that pertains to developing fundamental knowledge that will potentially help to reduce the burdens of human disease. The proposed research will be significant in the context of aging and cardiac dysfunction in trauma-hemorrhage, because it is expected to develop a tool and use it to elucidate the mitochondrial gene expression profile in the aging heart following trauma-hemorrhage.Narrative
The successful accomplishment of the objectives of this proposal would elucidate age related changes in mitochondrial gene expression in the heart after trauma-hemorrhage and the gene chip that will be developed as part of this project will have a broader use in aging and cardiovascular research.
描述(由申请人提供):了解衰老过程如何改变健康和疾病中的线粒体基因表达存在根本差距。众所周知,尽管液体复苏,但创伤性肿瘤休克后,心血管功能显着降低。由于在这些条件下线粒体功能也降低了,因此有关冲击后线粒体基因表达与年龄相关的信息的信息将有助于理解衰老和线粒体基因在心脏障碍中的作用,并有可能设计适当的干预策略。我们的长期目标是确定冲击和创伤后心脏线粒体基因改变的分子基础。我们的中心假设是,创伤性突击休克会导致心脏中线粒体基因表达的年龄特异性病理改变,可以使用线粒体基因芯片在实验模型中确定。该提案的目的是开发和验证啮齿动物线粒体基因芯片,并使用它来确定心脏线粒体基因表达的改变,这是在创伤性 - 突破性休克的大鼠模型中。 This objective will be achieved by pursuing the following three specific aims: (1) develop a rodent mitochondrial gene chip, RoMITOchip, to determine age related mitochondrial gene expression changes in an experimental model of trauma-hemorrhagic shock, ( 2) validate the RoMITOchip using (i)in vitro models of rat and mouse cardiomyocytes subjected to hypoxic and normoxic conditions, (ii) mice with线粒体功能的固有变化; (3)使用romitochip确定衰老在正常大鼠中衰老中的作用,以及一种大鼠的大鼠 - 毛发性休克的大鼠模型。线粒体基因组上的少量基因在Affymetrix大鼠或小鼠Genechip中没有表示。 Romitochip,我们的聚焦阵列将包括来自核基因组的基因,这些基因有助于线粒体DNA上的线粒体结构和功能以及基因,共同称为线粒体基因。我们将将大鼠和小鼠的线粒体基因纳入单个基因芯片,romitochip,并计划使用此工具来确定年轻大鼠创伤性 - 肌电疾病后心脏线粒体基因表达的变化。因此,拟议的研究与NIH任务的那部分有关,该任务与发展基本知识有关,这可能有助于减轻人类疾病的负担。拟议的研究将在创伤性 - 渗透性的衰老和心脏功能障碍的背景下具有重要意义
该提案的目标的成功实现将阐明创伤性恐惧后的线粒体基因表达与年龄相关的变化,并且作为该项目的一部分将开发的基因芯片将在衰老和心血管研究中更广泛使用。
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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Raghavan Pillai Raju其他文献
Raghavan Pillai Raju的其他文献
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Reparative effect of juvenile factors in aging and injury
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Reparative effect of juvenile factors in aging and injury
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INFLUENCE OF AGING ON MITOCHONDRIAL GENE EXPRESSION FOLLOWING TRAUMA-HEMORRHAGE
衰老对创伤出血后线粒体基因表达的影响
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