INVESTIGATION OF MITOCHONDRIAL DNA DAMAGE IN TFM-TREATED S CEREVISIAE

TFM 处理的酿酒酵母中线粒体 DNA 损伤的研究

• 批准号: 8360425
• 负责人: KAREN L HINKLE
• 金额: $ 2.66万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360425
• 关键词: Acids; Adult; Age; Aging; Bicarbonates; Biology; Birth; Cell membrane; Chloride Channels; DNA Damage; Development; Embryo; Embryonic Development; Funding; Gastric Acid; Gastric Parietal Cells; Gastrins; Gene Expression; Genes; Genetic; Genetically Engineered Mouse; Goals; Grant; Impairment; Investigation; Ion Exchange; Ion Transport; Mitochondrial DNA; Mus; National Center for Research Resources; Pattern; Potassium Channel; Principal Investigator; Regulation; Research; Research Infrastructure; Resources; Saccharomyces cerevisiae; Source; Staging; Stomach; System; Time; United States National Institutes of Health; Vermont; age related; aquaporin 4; cost; gastrointestinal; protein expression; water channel

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Previous studies have shown that proper ion exchange and transport across the parietal cell membrane is essential for normal gastric acid secretion. For example, genetically engineered mice deficient for the Na+/H+ exchangers Nhe2 and Nhe4, the Cl-/HCO3 exchanger Ae2, and the K+ channel Kvlqt1 showed significant impairments in acid secretion. In addition, achlorhydric gastrin-deficient mice showed alterations in gastric expression of the water channel aquaporin-4 (Aqp4) and the chloride channel Clca3. The patterns of gastric expression of these genes during embryonic development or as mice age is unknown. Gastric acid secretion is thought to be initiated immediately before parturition; in addition, evidence suggests that there is an increase in gastric acid secretion as mice age. Understanding the expression patterns of Aqp4, Clca3, Nhe2, Nhe4, Ae2, Kir2.1, and Kvlqt1 both in development and in aging mice may yield clues as to the timing of initiation of acid secretion as well as the age-related increase in acid levels. The overall goal of this research is to analyze developmental and age-related expression of various channels and exchangers important for normal acid secretion, including Aqp4, Clca3, Nhe2, Nhe4, Ae2, Kir2.1, and Kvlqt1. The hypothesis of this study is that the gastric expression of these genes increases at later embryonic developmental stages and increases as adult mice age. Specific Aim 1 will focus on gene expression analysis and gastric immunolocalization of candidate molecules during embryonic development. Specific Aim 2 will analyze gene and protein expression patterns of these candidates in aging wild-type and gastrin-deficient mice. Determining the expression patterns of these genes in murine embryonic development as well as in aging mice will allow a more thorough understanding of mechanisms that that regulate the gastric acid secretory system. This research will have an impact on the field of gastrointestinal biology by further elucidating the developmental and age-related regulation of gastric acid secretion.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其他NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 以前的研究表明，适当的离子交换和跨壁细胞膜的运输是正常的胃酸分泌所必需的。例如，缺乏Na+/H+交换器Nhe 2和Nhe 4、Cl-/HCO 3交换器Ae 2和K+通道Kvlqt 1的基因工程小鼠表现出酸分泌的显著损伤。此外，无胃酸胃泌素缺陷小鼠表现出胃水通道水通道蛋白4（Aqp 4）和氯离子通道Clca 3的表达改变。这些基因在胚胎发育过程中或随着小鼠年龄增长而在胃中表达的模式尚不清楚。胃酸分泌被认为是在分娩前立即开始的;此外，有证据表明，随着小鼠年龄的增长，胃酸分泌增加。了解Aqp 4，Clca 3，Nhe 2，Nhe 4，Ae 2，Kir2.1和Kvlqt 1在发育和衰老小鼠中的表达模式可能会产生关于酸分泌起始时间以及与年龄相关的酸水平增加的线索。本研究的总体目标是分析对正常酸分泌重要的各种通道和交换器的发育和年龄相关表达，包括Aqp 4，Clca 3，Nhe 2，Nhe 4，Ae 2，Kir2.1和Kvlqt 1。这项研究的假设是，这些基因的胃表达在胚胎发育后期增加，并随着成年小鼠年龄的增长而增加。具体目标1将集中在胚胎发育过程中的候选分子的基因表达分析和胃免疫定位。具体目标2将分析这些候选人在老龄野生型和胃泌素缺陷小鼠中的基因和蛋白质表达模式。确定这些基因在小鼠胚胎发育以及衰老小鼠中的表达模式，将使我们更深入地了解调节胃酸分泌系统的机制。这项研究将通过进一步阐明胃酸分泌的发育和年龄相关调节对胃肠道生物学领域产生影响。