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: 7725067
• 负责人: Argelia Lorence
• 金额: $ 8.58万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725067
• 关键词: Aging; Aging-Related Process; Animals; Antioxidants; Arabidopsis; Biological; Biomedical Research; Cells; Computer Retrieval of Information on Scientific Projects Database; Data; Depth; 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; Rate; 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; glucuronate reductase; inositol oxygenase; life history; mutant; reproductive; reproductive development; senescence; 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利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 衰老的氧化应激假说认为，与衰老相关的生理功能减退是由活性氧(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清楚地定义这种参与的性质。抗坏血酸(ASA)是细胞抗氧化能力的主要贡献者，细胞必须抵消ROS的作用。初步研究表明，在拟南芥植株的高ASA系中，有显著的迹象表明延长了寿命，延长了繁殖期，并增强了活力。这些表达肌醇(MI)途径基因到ASA(这条途径类似于动物途径到ASA的最后一步)的转基因基因，以及拟南芥的遗传和基因组资源，构成了一个强大的系统来探索ASA介导的抗衰老的机制和生物学基础，这在生物医学研究中具有重要意义。AIMS 1-3将测试这一假设，即抗坏血酸正在为高AsA拟南芥品系提供针对氧化胁迫的额外保护，并且这种保护对于这些植物表现出的延长寿命和延长生殖活动至关重要。 在目标1中，将描述ASA在调节生活史特征[生长、寿命、生殖活动持续时间和衰老]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连锁的AsA形成的途径(S)。我们建议利用我们为特定的AsA生物合成酶开发的基因敲除突变库来了解是否有与这种表型相关的途径。已知在拟南芥中，体细胞组织的寿命不受生殖发育的影响。在目标3中，将确定导致与延展开花表型连锁的AsA形成的途径(S)。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也更高。在目标4中，将测定MI途径到ASA的酶(MI加氧酶[MIOX]、葡萄糖醛酸还原酶、葡萄糖醛酸内酯酶和古龙酸-1，4-内酯氧化酶[GLOase])的细胞和亚细胞定位，以了解不同亚型在不同组织和细胞器中对ASA池的贡献。更深入和更好地了解细胞中的抗氧化活动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、动物和人类常见的过程。