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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 先前的研究表明，跨顶细胞膜的适当离子交换和转运对于正常的胃酸分泌至关重要。例如，缺乏Na+/H+交换器NHE2和NHE4的基因工程小鼠，Cl-/Hco3交换器AE2和K+通道KVLQT1在酸分泌中显示出重大损害。此外，缺乏胃胃胃磷脂的小鼠在水通道Aquaporin-4（AQP4）和氯化物通道CLCA3的胃表达中发生了变化。这些基因在胚胎发育或小鼠年龄期间这些基因的胃表达模式尚不清楚。胃酸分泌被认为是在分娩前立即开始的。此外，有证据表明，随着小鼠的年龄，胃酸分泌有所增加。了解AQP4，CLCA3，NHE2，NHE4，AE2，KIR2.1和KVLQT1在发育和衰老小鼠中的表达模式可能会产生有关酸性分泌的时间以及与年龄相关的酸水平的增加的线索。这项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展和年龄相关的表达，包括AQP4，CLCA3，NHE2，NHE4，NHE4，AE2，KIR2.1和KVLQT1。这项研究的假设是，这些基因的胃表达在以后的胚胎发育阶段增加，并且随着成年小鼠的年龄增长。具体目标1将集中于胚胎发育过程中候选分子的基因表达分析和胃免疫定位。特定的目标2将分析这些候选物的基因和蛋白质表达模式在老化的野生型和缺陷小鼠中。确定这些基因在鼠类胚胎发育以及衰老小鼠中的表达模式将使人们对调节胃酸分泌系统的机制有更透彻的了解。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来对胃肠道生物学领域产生影响。