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Potent reduction of apolipoprotein B and low-density lipoprotein cholesterol by short-term administration of an antisense inhibitor of apolipoprotein B.通过短期给予载脂蛋白B反义抑制剂有效降低载脂蛋白B和低密度脂蛋白胆固醇
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Knockdown of apolipoprotein B, an atherogenic apolipoprotein, in HepG2 cells by lentivirus-mediated siRNA.通过慢病毒介导的小干扰RNA（siRNA）敲低HepG2细胞中载脂蛋白B（一种致动脉粥样硬化的载脂蛋白）的表达。
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Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs.通过全身给予修饰的小干扰RNA对内源基因进行治疗性沉默。
Nature. 2004 Nov 11;432(7014):173-8. doi: 10.1038/nature03121.
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Ubiquitin-dependent and -independent proteasomal degradation of apoB associated with endoplasmic reticulum and Golgi apparatus, respectively, in HepG2 cells.在HepG2细胞中，载脂蛋白B分别在内质网和高尔基体中通过泛素依赖和非依赖的蛋白酶体途径降解。
J Cell Biochem. 2003 Aug 1;89(5):1019-29. doi: 10.1002/jcb.10538.
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Hammerhead ribozyme as a therapeutic agent for hyperlipidemia: production of truncated apolipoprotein B and hypolipidemic effects in a dyslipidemia murine model.锤头状核酶作为高脂血症的治疗药物：在血脂异常小鼠模型中截短载脂蛋白B的产生及降血脂作用
Hum Gene Ther. 2000 Nov 20;11(17):2415-30. doi: 10.1089/104303400750038516.
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Well-defined regions of apolipoprotein B-100 undergo conformational change during its intravascular metabolism.载脂蛋白B-100的明确区域在其血管内代谢过程中会发生构象变化。
Arterioscler Thromb Vasc Biol. 2000 May;20(5):1301-8. doi: 10.1161/01.atv.20.5.1301.
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Proteasome-mediated degradation of apolipoprotein B targets both nascent peptides cotranslationally before translocation and full-length apolipoprotein B after translocation into the endoplasmic reticulum.蛋白酶体介导的载脂蛋白B降解作用，既针对转运前共翻译过程中的新生肽，也针对转运至内质网后全长的载脂蛋白B。
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Intracellular antibodies (intrabodies) for gene therapy of infectious diseases.用于传染病基因治疗的细胞内抗体
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An inhibitor of the microsomal triglyceride transfer protein inhibits apoB secretion from HepG2 cells.微粒体甘油三酯转移蛋白抑制剂可抑制载脂蛋白B从HepG2细胞的分泌。
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Design, intracellular expression, and activity of a human anti-human immunodeficiency virus type 1 gp120 single-chain antibody.人抗人免疫缺陷病毒1型gp120单链抗体的设计、细胞内表达及活性
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载脂蛋白B细胞内抗体的克隆：在肝癌细胞系HepG2中特异性敲低载脂蛋白B

Cloning of apoB intrabodies: specific knockdown of apoB in HepG2 cells.

作者信息

Liao Wei, Strube Randall W, Milne Ross W, Chen Si-Yi, Chan Lawrence

机构信息

Department of Medicine and Molecular & Cellular Biology, Baylor College of Medicine, St. Luke's Episcopal Hospital, Houston, TX, USA.

出版信息

Biochem Biophys Res Commun. 2008 Aug 22;373(2):235-40. doi: 10.1016/j.bbrc.2008.06.020. Epub 2008 Jun 17.

DOI:10.1016/j.bbrc.2008.06.020
PMID:18558087
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2496960/
Abstract

Apolipoprotein (apo) B is essential for the assembly and secretion of triglyceride-rich lipoproteins made by the liver. As the sole protein component in LDL, apoB is an important determinant of atherosclerosis susceptibility and a potential pharmaceutical target. Single-chain antibodies (sFvs) are the smallest fragment of an IgG molecule capable of maintaining the antigen binding specificity of the parental antibody. In the present study, we describe the cloning and construction of two intracellular antibodies (intrabodies) to human apoB. We targeted these intrabodies to the endoplasmic reticulum for the purpose of retaining nascent apoB within the ER, thereby preventing its secretion. Expression of the 1D1 intrabody in the apoB-secreting human hepatoma cell line HepG2 resulted in marked reduction of apoB secretion. This study demonstrates the utility of an intrabody to specifically block the secretion of a protein determinant of plasma LDL as a therapeutic strategy for the treatment of hyperlipidemia.

摘要

载脂蛋白（apo）B对于肝脏合成和分泌富含甘油三酯的脂蛋白至关重要。作为低密度脂蛋白（LDL）中的唯一蛋白质成分，apoB是动脉粥样硬化易感性的重要决定因素，也是一个潜在的药物靶点。单链抗体（sFv）是能够保持亲本抗体抗原结合特异性的最小IgG分子片段。在本研究中，我们描述了两种针对人apoB的细胞内抗体（intrabodies）的克隆和构建。我们将这些细胞内抗体靶向内质网，目的是将新生的apoB保留在内质网中，从而阻止其分泌。1D1细胞内抗体在分泌apoB的人肝癌细胞系HepG2中的表达导致apoB分泌显著减少。本研究证明了细胞内抗体作为治疗高脂血症的治疗策略，特异性阻断血浆LDL蛋白质决定簇分泌的效用。