氧化低密度脂蛋白通过对咳毒素敏感的G蛋白通路降低内皮基础纤维细胞生长因子:血小板激活因子类脂的调解作用
1Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Circulation
|August 2, 2001
概括
氧化LDL (oxLDL) 通过降低基本纤维细胞生长因子 (bFGF) 的调节来抑制内皮细胞生长. 这通过一种对百日咳毒素敏感的G蛋白通路发生,涉及特定的脂.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 已知氧化LDL (oxLDL) 可以抑制血管生成.
- 这种抑制在一定程度上是由下调的内皮基本纤维细胞生长因子 (bFGF) 介导的.
- 精确的信号传导路径仍有待阐明.
研究的目的:
- 研究oxLDL对内皮bFGF进行下调的机制.
- 为了确定特定的信号传导途径和潜在的脂介质.
主要方法:
- 牛大动脉内皮细胞用PBS,LDL或oxLDL进行治疗.
- 细胞先用百日咳毒素 (PTX) 或特定途径抑制剂进行预处理.
- 评估了对bFGFmRNA,蛋白质和DNA合成的影响.
- 使用了血小板激活因子 (PAF) 受体对抗剂 (WEB 2086) 和PAF乙烯基酶.
主要成果:
- OxLDL显著降低了bFGF的mRNA,蛋白质和DNA合成.
- 咳毒素 (PTX) 的预处理阻断了oxLDL的抑制作用.
- 抑制MAPK,蛋白激酶和细胞内Ca2+的抑制剂并没有减弱oxLDL的影响.
- 一种PAF受体对抗剂阻断了oxLDL的作用,PAF降解消除了oxLDL的作用.
结论:
- 氧化的LDL抑制了内皮bFGF表达和DNA合成.
- 该机制涉及一个对PTX敏感的异构三基G蛋白通路.
- 与PAF相似但不完全相同的中间体脂含有.
相关概念视频
Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K
Regulation of Angiogenesis and Blood Supply
2.9K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.9K
TGF - β Signaling Pathway
7.2K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
Nitric Oxide Signaling Pathway
5.3K
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
5.3K
Coronary Artery Disease II: Pathophysiology
1.1K
Coronary Artery Disease (CAD) originates from a series of events that impair the function of coronary arteries, the blood vessels responsible for delivering oxygen-rich blood to the heart muscle. The pathophysiology of CAD is closely linked to atherosclerosis, a chronic inflammatory and lipid-driven condition affecting the vascular endothelium.1. Endothelial DamageThe process begins with damage to the vascular endothelium, which serves as a protective barrier between the blood and the vessel...
1.1K
Peripheral Artery Disease I: Introduction
663
Peripheral artery disease (PAD) predominantly results from atherosclerosis, which involves the accumulation of fatty deposits, or plaques, within the walls of arteries. This causes them to narrow and harden, significantly reducing blood flow. PAD predominantly affects the legs, particularly the arteries supplying the thighs and calves. In rare cases, it may involve other arteries, including those in the arms.Etiology of PAD:The principal cause of PAD is atherosclerosis, which results from fatty...
663


