Physiological and Pathological Aspects of Intestinal Vitamin B2 Absorption

肠道维生素 B2 吸收的生理和病理方面

基本信息

  • 批准号:
    9553448
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-07-01 至 2020-06-30
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): The long-term objectives of this renewal application continue to focus on investigating the cell/molecular physiology and pathophysiology of the intestinal vitamin B2 (riboflavin; RF) uptake process and of the factors that affect and interfere with the event. RF is essential for normal human health due to the key roles it plays in biological oxidation-reduction reactions involving lipid, carbohydrate and amino acid metabolism, and in the conversion of vitamin B6 and folate into their active forms. Recent findings have uncovered additional roles for RF in normal immune function, as an anti-inflammatory and anti-oxidant agent, and in the maintenance of normal intestinal homeostasis. Humans (mammals) cannot synthesize RF, and thus, must obtain the vitamin from exogenous sources via intestinal absorption. Studies from our laboratory and others have characterized different aspects of intestinal RF absorption and shown the process is specific and carrier-mediated; also all the three recently cloned RFVTs (RFVT-1, -2 & -3; products of the SLC52A1, SLC52A2 & SLC52A3 genes, respectively) are expressed in the intestine. In studies performed during the current funding period, we used an in vitro gene-silencing (siRNA) approach to show that the apically expressed RFVT-3 plays a major role in intestinal RF uptake. In new preliminary studies aimed at establishing the role of RFVT-3 in intestinal RF absorption in native intestine in vivo, we generated a conditional (intestinal-specific) SLC52A3 knockout (KO) mouse model and plan to use it to confirm and extend our in vitro findings. In other new preliminary studies, we have identified (via homology modeling/ligand docking analyses) putative structural features in the RFVT-3 protein that may be important for its function, obtained evidence implicating microRNAs (miRNAs) in post-transcriptional regulation of intestinal RF uptake, and have identified several potential interactig partners with RFVT-3 in intestinal epithelial cells. We also obtained evidence showing that infection of intestinal epithelial cells with S. Typhimurium, and exposure to pro-inflammatory cytokines and to bacterial LPS significantly lead to inhibition in intestinal RF uptake. Finally, w obtained new preliminary evidence suggesting possible involvement of epigenetic mechanism(s) in the inhibitory effect of chronic alcohol feeding on intestinal/colonic RF uptake that we observed during the current funding period. Based on our published studies and new preliminary findings, our working hypotheses in this proposal are that: 1) the RFVT-3 plays an important role in RF absorption in native intestine in vivo; that the transporter is post-transcriptionally regulated by microRNA; and that it has interacting partner(s) that may influence its physiology/cell biology; 2) Salmonella infection, and exposure to pro-inflammatory cytokines and to bacterial LPS inhibits intestinal RF uptake; and 3) the inhibitory effect of chronic alcohol exposure on SLC52A3 transcription in the intestine is mediated, at least in part, via epigenetic/molecular mechanism(s). Three specific aims are proposed to test these hypotheses and will utilize state-of-the-art in vivo and in vitro physiological, cellular, and molecular approaches. Results of these studies should continue to provide novel and valuable information regarding the cell/molecular physiology and pathophysiology of intestinal RF uptake and of external factors that affect and interfere with the process. This should ultimately assist us in th designing of effective strategies to optimize RF body homeostasis, especially in conditions associated with RF deficiency and sub-optimal levels.


项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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HAMID M SAID其他文献

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{{ truncateString('HAMID M SAID', 18)}}的其他基金

Physiology/Pathophysiology of Vitamin B1 Transport in Pancreatic Acinar Cells
胰腺腺泡细胞中维生素 B1 运输的生理学/病理生理学
  • 批准号:
    10799411
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
Effect of Pathophysiological Conditions on Intestinal Absorption of Free Thiamin
病理生理条件对游离硫胺素肠道吸收的影响
  • 批准号:
    10246647
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
Effect of Pathophysiological Conditions on Intestinal Absorption of Free Thiamin
病理生理条件对游离硫胺素肠道吸收的影响
  • 批准号:
    10651601
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
BLRD Research Career Scientist Award Application
BLRD 研究职业科学家奖申请
  • 批准号:
    10585365
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
Mechanism/Regulation of Intestinal Thiamin Uptake
肠道硫胺素摄取的机制/调节
  • 批准号:
    8791430
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:
Mechanism/Regulation of Intestinal Thiamin Uptake
肠道硫胺素摄取的机制/调节
  • 批准号:
    9087015
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:
Physiological and Pathological Aspects of Intestinal Vitamin B2 Absorption
肠道维生素 B2 吸收的生理和病理方面
  • 批准号:
    9026398
  • 财政年份:
    2012
  • 资助金额:
    --
  • 项目类别:
Physiological and Pathological Aspects of Intestinal Vitamin B2 Absorption
肠道维生素 B2 吸收的生理和病理方面
  • 批准号:
    9215519
  • 财政年份:
    2012
  • 资助金额:
    --
  • 项目类别:
Intestinal Vitamin B2 Absorption: Molecular/Cellular Aspects and Effects of Alcoh
肠道维生素 B2 吸收:分子/细胞方面和酒精的影响
  • 批准号:
    8803250
  • 财政年份:
    2011
  • 资助金额:
    --
  • 项目类别:
Intestinal Vitamin B2 Absorption: Molecular/Cellular Aspects and Effects of Alcoh
肠道维生素 B2 吸收:分子/细胞方面和酒精的影响
  • 批准号:
    8139616
  • 财政年份:
    2011
  • 资助金额:
    --
  • 项目类别:

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