细胞内tPA-PAI-1相互作用决定了肝细胞中的VLDL组合
Wen Dai1, Heng Zhang1, Hayley Lund2
1Versiti Blood Research Institute, Milwaukee, WI 53226, USA.
概括
组织等离子素激活剂 (tPA) 通过阻断其与肝细胞中MTP的相互作用来降低血蛋白B. 血原激活剂抑制剂1 (PAI-1) 逆转这种作用,影响VLDL组合和胆固醇水平.
科学领域:
- 生物化学
- 心血管生物学
- 分子医学
背景情况:
- 阿波脂蛋白B (apoB) - 脂蛋白是动脉样硬化心血管疾病的关键驱动因素.
- 血组织等离子素激活剂 (tPA) 的活性与动脉质B脂蛋白胆固醇相反相关,但潜在的机制尚不清楚.
研究的目的:
- 阐明将血tPA活性与apoB脂蛋白胆固醇水平联系起来的分子机制.
- 研究tPA,PAI-1和MTP在肝细胞内非常低密度脂蛋白 (VLDL) 组合中的作用.
主要方法:
- 使用生物化学测试研究了tPA和apoB之间的相互作用.
- 研究了tPA与微体甘油转移蛋白 (MTP) 相互作用的影响.
- 评估了塑原激活剂抑制剂1 (PAI-1) 对tPA-apoB相互作用和VLDL组合的影响.
主要成果:
- 组织等离子素激活剂 (tPA) 直接与阿波利波蛋白B (apoB) 的N端结合,利用其Kringle 2域的素结合位.
- 这种tPA- apoB相互作用抑制了apoB与肝细胞中的微体甘油三转移蛋白 (MTP) 的结合.
- 因此,tPA降低了极低密度脂蛋白 (VLDL) 的组合,并降低了血的ApoB脂蛋白胆固醇水平.
- 血原激活剂抑制剂1 (PAI-1) 通过隔离tPA来对抗tPA的作用,从而促进VLDL组合.
- 患有PAI-1 缺乏症的个体表现出较小的VLDL 颗粒和降低的血ApoB-脂蛋白胆固醇.
结论:
- 一种新的细胞内机制通过tPA,PAI-1和apoB在肝细胞内的相互作用来调节VLDL组合.
- 这种相互作用提供了tPA活性与动脉动脉B脂蛋白胆固醇水平调节之间的分子联系.
更多相关视频
11:34A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
2.3K
08:53Using Scaffold Liposomes to Reconstitute Lipid-proximal Protein-protein Interactions In Vitro
Published on: January 11, 2017
8.9K
相关概念视频
Phosphoinositides and PIPs
8.6K
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.6K
Receptor-mediated Endocytosis
104.7K
Overview
104.7K
Intracellular Signaling Affects Focal Adhesions
2.7K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.7K
Coat Assembly and GTPases
3.6K
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
3.6K
IP3/DAG Signaling Pathway
12.2K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
12.2K
Lipids as Anchors
5.7K
In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
5.7K
