Vitamin E metabolism and lung toxicology
维生素 E 代谢和肺毒理学
基本信息
- 批准号:6889547
- 负责人:
- 金额:$ 31.64万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-05-01 至 2007-03-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant): Oxidant-induced respiratory tract injury (caused by cigarette smoke (CS), ozone (03) or endogenous inflammatory-immune processes) is influenced by both low molecular weight (e.g. antioxidant micronutrients, GSH) and enzymatic antioxidant defenses. The proposed studies are built around the thesis that the (-tocopherol transfer protein ((-TTP) knockout mouse is an appropriate model to study molecular mechanisms underlying (-T trafficking in the lung and (-T's influence on oxidative and inflammatory-immune cell injury. To test the hypothesis that lung (-T status is 1) actively regulated by lung Type II cell transmembrane and intraceilular lipid transporters, 2) these transporters are modulated under oxidative stress induced by exposure to CS, to 03 or inflammation induced by lipopolysaccharide, and 3) inflammation induced by these toxicants is modulated by (-T and (-T, we propose three aims: (i) to identify mechanisms of (-T regulation and metabolism in lung Type II cells; (ii) to confirm (-T specificity by alleviating oxidative stress by feeding diets containing exclusively (-T to (-TTP knockout mice, which have very low plasma and tissue ((-T levels; and (iii) to further define the roles of (-T and (-T in modulating inflammatory responses of the respiratory tract to CS, 03 and LPS-induced lung challenge. Our research strategies will initially center on Type II cell (-T metabolism because these cells secrete (-T into lung lining fluid and possess incompletely characterized receptor, transport and secretory pathways specific for (-T. (- T-replete-mice will be compared with (-T-replete mice, which will alleviate oxidant effect and allow evaluation of possible discordant effects on modulation of lung oxidative/inflammatory injurious responses. Our research plan also includes protocols designed to evaluate for "non-antioxidant" functions of (-T as compared with (-T. The results of our proposed studies are expected to provide important information regarding optimal forms and intakes of vitamin E for prevention and/or amelioration of pulmonary diseases, most notably those characterized by activated inflammatory-immune system responses.
描述(由申请人提供):氧化剂诱导的呼吸道损伤(由香烟烟雾(CS),臭氧(03)或内源性炎症免疫过程引起)受低分子量(例如抗氧化微量营养素,GSH)和酶促抗氧化防御的影响。提出的研究是围绕(-生育酚转移蛋白(-TTP)敲除小鼠是研究(-T)在肺部运输的分子机制以及(-T)对氧化和炎症免疫细胞损伤的影响的合适模型。为了验证肺(-T)状态由肺II型细胞跨膜和细胞内脂质转运体主动调节,2)这些转运体在暴露于CS、03或脂多糖诱导的炎症诱导的氧化应激下被调节,以及3)这些毒物诱导的炎症被(-T和(-T)调节的假设,我们提出了三个目标:(i)确定肺II型细胞(-T)调节和代谢的机制;(ii)通过饲喂血浆和组织中(-T)水平非常低的(-T至(-TTP)敲除小鼠,通过减轻氧化应激来确认(-T特异性);(iii)进一步确定(-T和(-T)在调节呼吸道对CS、03和lps诱导的肺部攻击的炎症反应中的作用。我们的研究策略最初将集中于II型细胞(t)代谢,因为这些细胞将(t)分泌到肺内膜液中,并且具有不完全表征的(t)特异性受体、运输和分泌途径。(- t - fill -小鼠将与(- t - fill -小鼠进行比较,这将减轻氧化效应,并允许评估在肺氧化/炎症损伤反应调节方面可能存在的不一致效应。我们的研究计划还包括设计方案来评估(t -T与(t -T相比的“非抗氧化”功能。我们提出的研究结果有望提供有关维生素E的最佳形式和摄入量的重要信息,以预防和/或改善肺部疾病,特别是那些以激活的炎症免疫系统反应为特征的疾病。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
CARROLL E CROSS其他文献
CARROLL E CROSS的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('CARROLL E CROSS', 18)}}的其他基金
Therapeutic Targeting of Myeloperoxidase in Acute Inflammation
急性炎症中髓过氧化物酶的治疗靶向
- 批准号:
7922100 - 财政年份:2009
- 资助金额:
$ 31.64万 - 项目类别:
Therapeutic Targeting of Myeloperoxidase in Acute Inflammation
急性炎症中髓过氧化物酶的治疗靶向
- 批准号:
7661338 - 财政年份:2009
- 资助金额:
$ 31.64万 - 项目类别:
NITRIC OXIDE-MEDIATED PROTEIN MODIFICATION IN THE LUNG
一氧化氮介导的肺部蛋白质修饰
- 批准号:
6030791 - 财政年份:1997
- 资助金额:
$ 31.64万 - 项目类别:
NITRIC OXIDE-MEDIATED PROTEIN MODIFICATION IN THE LUNG
一氧化氮介导的肺部蛋白质修饰
- 批准号:
2735360 - 财政年份:1997
- 资助金额:
$ 31.64万 - 项目类别:
NITRIC OXIDE-MEDIATED PROTEIN MODIFICATION IN THE LUNG
一氧化氮介导的肺部蛋白质修饰
- 批准号:
2409289 - 财政年份:1997
- 资助金额:
$ 31.64万 - 项目类别:
OXIDANT AIR POLLUTANT EFFECTS ON LUNG LINING FLUID(S)
氧化剂空气污染物对肺内液的影响
- 批准号:
3366854 - 财政年份:1992
- 资助金额:
$ 31.64万 - 项目类别:
LUNG SURFACE ANTIOXIDANT DEFENSES AGAINST AIR POLLUTANTS
肺表面抗氧化防御空气污染物
- 批准号:
6017254 - 财政年份:1992
- 资助金额:
$ 31.64万 - 项目类别:
OXIDANT AIR POLLUTANT EFFECTS ON LUNG LINING FLUID(S)
氧化剂空气污染物对肺内液的影响
- 批准号:
2223819 - 财政年份:1992
- 资助金额:
$ 31.64万 - 项目类别:
相似海外基金
In Vitro Dispersion Studies of Airborne Allergen Particles
空气中过敏原颗粒的体外分散研究
- 批准号:
564075-2021 - 财政年份:2021
- 资助金额:
$ 31.64万 - 项目类别:
University Undergraduate Student Research Awards