ROLE OF ASCORBATE IN COORDINATING GROWTH & SENESCENCE IN ARABIDOPSIS THALIANA

抗坏血酸在协调生长中的作用

• 批准号: 7959434
• 负责人: Argelia Lorence
• 金额: $ 8.52万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959434
• 关键词: Aging; Aging-Related Process; Animals; Antioxidants; Arabidopsis; Arkansas; Biological; Biomedical Research; Cells; Computer Retrieval of Information on Scientific Projects Database; Data; Enzymes; Flowers; Funding; Genes; Genetic; Genomics; Grant; Growth; Human; Inositol; Institution; Knock-out; Lactones; Learning; Length; Link; Longevity; Mediating; Metabolic; Molecular; Mouse-ear Cress; Nature; Organelles; Oxidases; Oxidative Stress; Pathway interactions; Phenotype; Physiological; Plants; Process; Protein Isoforms; Reactive Oxygen Species; Reproductive Periods; Research; Research Personnel; Resistance; Resources; Role; Route; Source; System; Testing; Tissues; Transgenic Organisms; United States National Institutes of Health; ascorbate; attenuation; base; combat; glucuronate reductase; inositol oxygenase; life history; mutant; oxidative damage; reproductive; reproductive development; senescence; therapy development; trait; uronolactonase

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 oxidative stress hypothesis of aging postulates that senescence-associated attenuations in physiological function are caused by molecular oxidative damage induced by reactive oxygen species (ROS). Although there is considerable evidence implicating oxidative stress in aging, additional data are needed to clearly define the nature of this involvement. Ascorbate (AsA) is a major contributor to the antioxidant capacity cells have to counteract the action of ROS. Preliminary studies have shown significant signs of enhanced longevity, expanded reproductive period, and increased vigor in high-AsA lines of the Arabidopsis thaliana plant. These transgenics expressing genes of the myo-inositol (MI) pathway to AsA (a route that resembles the last steps of the animal pathway to AsA), and the genetic and genomic resources of Arabidopsis constitute a powerful system to explore the mechanisms and biological basis of an AsA-mediated resistance to aging, a subject of significant importance in biomedical research. Aims 1-3 will test the hypothesis that ascorbate is providing high-AsA Arabidopsis lines additional protection against oxidative stress, and that this protection is critical for the increased lifespan and extended reproductive activity displayed by those plants. In Aim 1, the role of AsA in modulating the temporal control of life-history traits [growth, lifespan, length of reproductive activity, and senescence] will be characterized. In Aim 2, the route(s) leading to AsA formation linked to the extended longevity phenotype will be determined. We propose leveraging the repertoire of knockout mutants we have developed for specific AsA biosynthetic enzymes to learn if there is a pathway linked to this phenotype. It is known that in Arabidopsis, somatic tissue longevity is not governed by reproductive development. In Aim 3, the route(s) leading to AsA formation linked to the extended flowering phenotype will be determined. Reproductive and actively growing tissues have higher metabolic rates and, therefore, a higher demand for antioxidants. In Aim 4, the cellular and subcellular localization of enzymes of the MI pathway to AsA (MI oxygenase [MIOX], glucuronate reductase, glucuronolactonase and gulono-1,4-lactone oxidase [GLOase]) will be determined in order to learn about the contribution of the different isoforms to the AsA pool in various tissues and organelles. A deeper and better understanding of the antioxidant activities in cells will contribute to developing therapies to combat/retard some of the destructive processes associated with aging, processes common to plants, animals, and humans.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 衰老的氧化应激假说认为，衰老相关的生理功能衰减是由活性氧（ROS）诱导的分子氧化损伤引起的。虽然有相当多的证据表明氧化应激与衰老有关，但还需要更多的数据来明确定义这种参与的性质。抗坏血酸（阿萨）是细胞对抗ROS作用的抗氧化能力的主要贡献者。初步研究表明，在拟南芥植物的高AsA品系中，显著的迹象是寿命延长、生殖期延长和活力增加。这些转基因表达的肌醇（MI）途径的基因阿萨（一条路线，类似于动物途径的最后几步阿萨），和遗传和基因组资源的拟南芥构成了一个强大的系统，探索机制和生物学基础的AsA介导的抗衰老，在生物医学研究中的一个重要课题。目的1-3将测试的假设，抗坏血酸是提供高抗坏血酸拟南芥线额外的保护氧化应激，这种保护是至关重要的寿命延长和延长生殖活性显示这些植物。 在目标1中，将描述阿萨在调节生活史特征[生长、寿命、生殖活动长度和衰老]的时间控制中的作用。在目标2中，将确定导致与延长寿命表型相关的阿萨形成的途径。我们建议利用我们为特定的阿萨生物合成酶开发的敲除突变体库来了解是否存在与这种表型相关的途径。已知在拟南芥中，体细胞组织寿命不受生殖发育的控制。在目标3中，将确定导致与延长开花表型相关的阿萨形成的途径。生殖和活跃生长的组织具有更高的代谢率，因此对抗氧化剂的需求更高。在目的4中，将确定MI途径酶（MI加氧酶[MIOX]、葡萄糖醛酸还原酶、葡萄糖醛酸内酯酶和古洛糖酸-1，4-内酯氧化酶[GLOase]）对阿萨的细胞和亚细胞定位，以了解不同亚型对各种组织和细胞器中阿萨库的贡献。更深入和更好地了解细胞中的抗氧化活性将有助于开发治疗方法，以对抗/延缓与衰老相关的一些破坏性过程，这些过程是植物，动物和人类共同的过程。