Functions of vitamin E and the tocopherol transfer protein
维生素 E 和生育酚转移蛋白的功能
基本信息
- 批准号:10394948
- 负责人:
- 金额:$ 62.47万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-20 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffinityAnimal BehaviorAntioxidantsAreaBindingBiochemistryBiologicalBiologyBiophysicsBrainCell membraneCellsCellular biologyCerebellumCirrhosisClinical TrialsDietary ComponentDietary FatsDiseaseEpidemicFatty LiverFatty acid glycerol estersFibrosisFree RadicalsFutureGene ExpressionGene Expression ProfileGenetic ModelsGenetic TranscriptionGenomicsGoalsHealthHealth PromotionHepaticHepatocyteHeritabilityHomeostasisHumanIn VitroInflammationLipid PeroxidationLipidsLipoproteinsLiverLiver diseasesMediatingMembraneMembrane ProteinsMolecularMouse ProteinMutationNervous System TraumaNervous system structureNeuraxisNeurologicNeurologic DysfunctionsNucleic AcidsNutrientObesityOnline Mendelian Inheritance In ManOrganellesOrganic ChemistryOrganismOutcomePathologicPathologyPatientsPhosphatidylinositolsPhysiologicalPlantsPlayProcessProteinsResearchRiskRoleSiteSupplementationTTPA geneTestingTherapeutic InterventionTissuesTocopherolsVertebratesVitamin EVitamin E DeficiencyVitaminsalpha Tocopherolalpha-tocopherol transfer proteinataxia with vitamin E deficiencydesigndietaryeffective interventionhuman diseasein vivoinsightliver injuryliver transplantationmolecular imagingmouse modelmultidisciplinarynervous system disordernon-alcoholic fatty liver diseasenonalcoholic steatohepatitisnovelpreventprotein functionprotein transportsevere injurytraffickingtraittranscription factortranslational impactvesicle transportvitamin analog
项目摘要
Alpha-tocopherol (vitamin E) is an essential nutrient and the major fat-soluble antioxidant in humans. The most critical health-promoting action of vitamin E is thought to be anchored in protecting the central nervous system (CNS) from damage to membranes, proteins and nucleic acids induced by reactive species or free radicals. The levels and distribution of vitamin E in the body are regulated by hepatic alpha tocopherol transfer protein (TTP), which regulates secretion of the vitamin from the liver to circulating lipoproteins, and in turn to all tissues. Accordingly, mutations in the TTPA gene are the only known cause for ataxia with vitamin E deficiency (AVED; OMIM 277460). Our studies over the years have identified critical functions and mechanisms of action of a-tocopherol and TTP and we have made important discoveries that detail how TTP transports the vitamin across cells in the liver and the cerebellum. The proposed research will focus on three areas of critical importance: 1) we will decipher the molecular mechanisms underlying TTP-facilitation of trafficking of a- tocopherol from the endocytic compartment to the plasma membrane. 2) We will examine the molecular mechanisms and physiological consequences of novel, antioxidant independent activities of vitamin E, and their consequences on neurological health in a mouse model of vitamin E deficiency. 3) We will decipher the mechanisms by which vitamin E prevents the pathological progression of non alcoholic fatty liver disease to severe, irreversible liver disease (non alcoholic steatohepatitis). The results from our studies will provide important new insight into the role of vitamin E in health and disease.
α -生育酚(维生素E)是人体必需的营养素和主要的脂溶性抗氧化剂。维生素E最重要的健康促进作用被认为是保护中枢神经系统(CNS)免受活性物质或自由基引起的膜、蛋白质和核酸损伤。体内维生素E的水平和分布受肝脏α -生育酚转移蛋白(TTP)的调节,该蛋白调节维生素E从肝脏向循环脂蛋白的分泌,进而向所有组织输送。因此,TTPA基因突变是维生素E缺乏症共济失调的唯一已知原因(AVED; OMIM 277460)。多年来,我们的研究已经确定了a-生育酚和TTP的关键功能和作用机制,我们也有了重要的发现,详细说明了TTP如何在肝脏和小脑的细胞之间运输维生素。建议的研究将集中在三个至关重要的领域:1)我们将破译ttp促进从内噬室到质膜的a-生育酚运输的分子机制。2)我们将在维生素E缺乏的小鼠模型中研究维生素E的分子机制和新的抗氧化独立活性的生理后果,以及它们对神经健康的影响。3)我们将破译维生素E防止非酒精性脂肪性肝病病理进展为严重的,不可逆的肝脏疾病(非酒精性脂肪性肝炎)的机制。我们的研究结果将为维生素E在健康和疾病中的作用提供重要的新见解。
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 }}
DANNY MANOR其他文献
DANNY MANOR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('DANNY MANOR', 18)}}的其他基金
Understanding and Targeting Tiam1 in Cancer
了解 Tiam1 并针对癌症进行靶向治疗
- 批准号:
10322680 - 财政年份:2021
- 资助金额:
$ 62.47万 - 项目类别:
Functions of vitamin E and the tocopherol transfer protein
维生素 E 和生育酚转移蛋白的功能
- 批准号:
10541855 - 财政年份:2021
- 资助金额:
$ 62.47万 - 项目类别:
Understanding and Targeting Tiam1 in Cancer
了解 Tiam1 并针对癌症进行靶向治疗
- 批准号:
10093529 - 财政年份:2021
- 资助金额:
$ 62.47万 - 项目类别:
相似海外基金
Construction of affinity sensors using high-speed oscillation of nanomaterials
利用纳米材料高速振荡构建亲和传感器
- 批准号:
23H01982 - 财政年份:2023
- 资助金额:
$ 62.47万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Affinity evaluation for development of polymer nanocomposites with high thermal conductivity and interfacial molecular design
高导热率聚合物纳米复合材料开发和界面分子设计的亲和力评估
- 批准号:
23KJ0116 - 财政年份:2023
- 资助金额:
$ 62.47万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Development of High-Affinity and Selective Ligands as a Pharmacological Tool for the Dopamine D4 Receptor (D4R) Subtype Variants
开发高亲和力和选择性配体作为多巴胺 D4 受体 (D4R) 亚型变体的药理学工具
- 批准号:
10682794 - 财政年份:2023
- 资助金额:
$ 62.47万 - 项目类别:
Platform for the High Throughput Generation and Validation of Affinity Reagents
用于高通量生成和亲和试剂验证的平台
- 批准号:
10598276 - 财政年份:2023
- 资助金额:
$ 62.47万 - 项目类别:
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
- 批准号:
2233343 - 财政年份:2023
- 资助金额:
$ 62.47万 - 项目类别:
Standard Grant
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
- 批准号:
2233342 - 财政年份:2023
- 资助金额:
$ 62.47万 - 项目类别:
Standard Grant
Molecular mechanisms underlying high-affinity and isotype switched antibody responses
高亲和力和同种型转换抗体反应的分子机制
- 批准号:
479363 - 财政年份:2023
- 资助金额:
$ 62.47万 - 项目类别:
Operating Grants
Deconstructed T cell antigen recognition: Separation of affinity from bond lifetime
解构 T 细胞抗原识别:亲和力与键寿命的分离
- 批准号:
10681989 - 财政年份:2023
- 资助金额:
$ 62.47万 - 项目类别:
CAREER: Engineered Affinity-Based Biomaterials for Harnessing the Stem Cell Secretome
职业:基于亲和力的工程生物材料用于利用干细胞分泌组
- 批准号:
2237240 - 财政年份:2023
- 资助金额:
$ 62.47万 - 项目类别:
Continuing Grant
ADVANCE Partnership: Leveraging Intersectionality and Engineering Affinity groups in Industrial Engineering and Operations Research (LINEAGE)
ADVANCE 合作伙伴关系:利用工业工程和运筹学 (LINEAGE) 领域的交叉性和工程亲和力团体
- 批准号:
2305592 - 财政年份:2023
- 资助金额:
$ 62.47万 - 项目类别:
Continuing Grant