Relationship of Apo B and BHMT: Nutrition and Physiology
Apo B 和 BHMT 的关系:营养和生理学
基本信息
- 批准号:6434461
- 负责人:
- 金额:$ 19.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-09-30 至 2005-08-31
- 项目状态:已结题
- 来源:
- 关键词:apolipoprotein B betaine compound cell line diet gene environment interaction gene expression gene targeting genetically modified animals homocysteine immunoprecipitation laboratory mouse laboratory rabbit laboratory rat liver cells liver metabolism messenger RNA methylation methyltransferase nutrition related tag protein metabolism protein protein interaction radioassay tissue /cell culture transfection
项目摘要
DESCRIPTION (provided by applicant): Apolipoprotein B (Apo B) is important in lipid transport in lipoproteins (LP), and as a factor associated with risk of macrovascular disease complications (heart attacks, strokes). B48 and B100 are forms of apo B that, in humans, represent intestinal and hepatic products of translation that are derived from edited and unedited apo B mRNA transcribed from a single copy gene.
In McArdle RH-7777 (McA) cells, the restoration of betaine homocysteine S-methyltransferase (BHMT) expression through transfection is positively correlated with apo B mRNA abundance and increases in B48 and B100 secretion. BHMT catalyzes transfer of a methyl group from betaine to homocysteine to form methionine. BHMT and methionine synthase contribute
equally to methionine formation from homocysteine in rat liver. BHMT can be induced in a variety of nutritional states in vivo.
Aim 1 is to establish the physiological relationship between BHMT and apo B. Using dietary conditions that alter BHMT expression, changes in apo B mRNA will be evaluated in rats.
Aim 2 will evaluate the impact of apo B mRNA and BHMT pathways on hepatic lipoprotein metabolism in rat hepatocytes (RH) and BHMT-transfected McA cells. Hepatic biogenesis of B100 and B48 will be studied including apo B translation, intracellular LP assembly, apo B degradation, and LP secretion. In order to assess mechanisms of apo B mRNA abundance changes, apo B mRNA stability and apo B gene transcription will be documented. BHMT may function in hepatic lipid metabolism directly, and experiments will test whether BHMT mediates methyl transfer from betaine to phosphatidylethanolamine in the formation of phosphatidyicholme necessary in apo B-Lp secretion.
The overall research goal is to understand and characterize BHMT metabolic pathways and potential relationships to apo B biogenesis. A potential link of two pathways whose products or intermediates are associated with increased cardiovascular disease risk could be established.
描述(由申请方提供):载脂蛋白B(Apo B)在脂蛋白(LP)中的脂质转运中很重要,是与大血管疾病并发症(心脏病发作、中风)风险相关的一个因素。B48和B100是apo B的形式,在人类中,它们代表肠和肝翻译产物,这些产物来源于从单拷贝基因转录的编辑和未编辑的apo B mRNA。
在McArdle RH-7777(McA)细胞中,通过转染恢复甜菜碱同型半胱氨酸S-甲基转移酶(BHMT)表达与载脂蛋白B mRNA丰度和B48和B100分泌增加呈正相关。BHMT催化甲基从甜菜碱转移到高半胱氨酸以形成甲硫氨酸。BHMT和甲硫氨酸合酶
这与大鼠肝脏中同型半胱氨酸形成甲硫氨酸相同。BHMT可以在体内多种营养状态下诱导。
目的1.建立BHMT与载脂蛋白B的生理关系。使用改变BHMT表达的饮食条件,评价大鼠中apo B mRNA的变化。
目的2在大鼠肝细胞(RH)和转染BHMT的McA细胞中评价载脂蛋白B mRNA和BHMT通路对肝脂蛋白代谢的影响。将研究B100和B48的肝脏生物合成,包括apo B翻译、细胞内LP组装、apo B降解和LP分泌。为了评估载脂蛋白B mRNA丰度变化的机制,将记录载脂蛋白B mRNA稳定性和载脂蛋白B基因转录。BHMT可能直接在肝脏脂质代谢中起作用,并且实验将测试BHMT是否介导在apo B-Lp分泌所必需的磷脂酰胆碱形成中从甜菜碱到磷脂酰乙醇胺的甲基转移。
总体研究目标是了解和表征BHMT代谢途径和与载脂蛋白B生物发生的潜在关系。可以建立两种途径的潜在联系,其产物或中间体与心血管疾病风险增加相关。
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)
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JANET DEHOFF SPARKS其他文献
JANET DEHOFF SPARKS的其他文献
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{{ truncateString('JANET DEHOFF SPARKS', 18)}}的其他基金
Postprandial insulin regulation of B100 and importance to VLDL1 secretion
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- 批准号:
8837624 - 财政年份:2014
- 资助金额:
$ 19.69万 - 项目类别:
Postprandial insulin regulation of B100 and importance to VLDL1 secretion
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- 批准号:
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- 资助金额:
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Hepatic Steatosis Modulation by Apo B Gene Transcription
Apo B 基因转录调节肝脂肪变性
- 批准号:
8012888 - 财政年份:2010
- 资助金额:
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Hepatic Steatosis Modulation by Apo B Gene Transcription
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7595921 - 财政年份:2008
- 资助金额:
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Relationship of Apo B and BHMT: Nutrition and Physiology
Apo B 和 BHMT 的关系:营养和生理学
- 批准号:
6795467 - 财政年份:2002
- 资助金额:
$ 19.69万 - 项目类别:
Relationship of Apo B and BHMT: Nutrition and Physiology
Apo B 和 BHMT 的关系:营养和生理学
- 批准号:
6660711 - 财政年份:2002
- 资助金额:
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INSULIN PI 3 KINASE AND APO B BIOGENESIS IN OBESE RATS
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- 批准号:
2151405 - 财政年份:1996
- 资助金额:
$ 19.69万 - 项目类别:
INSULIN PI 3 KINASE AND APO B BIOGENESIS IN OBESE RATS
肥胖大鼠中胰岛素 PI 3 激酶和 APO B 生物发生
- 批准号:
2770537 - 财政年份:1995
- 资助金额:
$ 19.69万 - 项目类别:
Insulin regulated hepatic apo B lipoprotein biogenesis
胰岛素调节肝脏载脂蛋白 B 脂蛋白生物发生
- 批准号:
6874294 - 财政年份:1995
- 资助金额:
$ 19.69万 - 项目类别:
Insulin regulated hepatic apo B lipoprotein biogenesis
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- 批准号:
6517371 - 财政年份:1995
- 资助金额:
$ 19.69万 - 项目类别: