MODULATION OF APOLIPOPROTEIN B GENE EXPRESSION

载脂蛋白 B 基因表达的调节

• 批准号: 3858027
• 负责人: A P PATTERSON
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3858027
• 关键词: apolipoproteins; blood lipoprotein biosynthesis; chylomicrons; developmental genetics; dietary lipid; gene expression; hormone regulation /control mechanism; human tissue; laboratory rat; lipid transport; liver metabolism; low density lipoprotein; posttranscriptional RNA processing; posttranslational modifications; small intestines; thyroid hormones; very low density lipoprotein

Apolipoprotein B is the principal apolipoprotein on chylomicrons, ow density lipoproteins, intermediate lipoproteins, and low density lipoproteins. Apolipoprotein B exists in human plasma in two forms, the full length apoB-100 and the shorter apoB-48. ApoB-100 is synthesized primarily by the liver, whereas apoB-48 is derived exclusively from the small intestine. Both forms of the protein are requisite for the normal transport and delivery of dietary and endogenous lipids to target tissues. Both proteins are the product of a single gene which encodes a mRNA that may either be directly translated into the full-length apoB-100 or, alternatively, be modified by conversion of single nucleotide that results in the replacement of the codon CAA at position 2153 with the premature STOP codon UAA. This modification results in the shorter translation product apoB-48 and is referred to as mRNA "editing." By analysis of mRNA derived from human and rat tissues at various stages of development, our laboratory this year has demonstrated that the capacity to edit apoB mRNA is developmentally controlled in a -tissue and species-specific manner. Furthermore, we have demonstrated that one of the requisite developmental tissue-specific signals is thyroid hormone: in the absence of thyroid hormone normal editing does not develop in the liver, while the small intestine edits normally; administration of thyroid hormone can restore normal editing in the developing liver.

载脂蛋白B是乳糜微粒上的主要载脂蛋白， 密度脂蛋白、中等密度脂蛋白和低密度脂蛋白 脂蛋白 载脂蛋白B以两种形式存在于人血浆中， 全长apoB-100和较短的apoB-48。 合成ApoB-100 主要是由肝脏，而apoB-48是完全来自 小肠 这两种形式的蛋白质是必需的正常 将膳食和内源性脂质运输和递送至目标 组织中 这两种蛋白质都是同一个基因的产物， mRNA可以直接翻译成全长apoB-100 或者可选择地，通过转化单核苷酸进行修饰， 导致2153位的密码子CAA被替换为 提前终止密码子UAA。 这种修改导致较短的 翻译产物apoB-48，被称为mRNA“编辑”。“由 分析来自人和大鼠组织在不同阶段的mRNA， 我们的实验室今年已经证明， 编辑apoB mRNA在组织中受到发育控制， 物种特有的方式。此外，我们已经证明， 必要的发育组织特异性信号是甲状腺激素： 在没有甲状腺激素的情况下， 肝脏，而小肠正常编辑;施用 甲状腺激素可以恢复发育中肝脏的正常编辑。