通过血红氧酶-1的负调节可溶性Flt-1和可溶性内分泌物释放
Melissa Cudmore1, Shakil Ahmad, Bahjat Al-Ani
1Department of Reproductive and Vascular Biology, Medical School, University of Birmingham, Edgbaston, Birmingham, West Midlands, B15 2TT, UK.
Circulation
|March 29, 2007
概括
血红素酶-1 (HO-1) 途径,产生一氧化碳 (CO),抑制了孕前标记物可溶性Flt-1 (sFlt-1) 和可溶性内分泌素 (sEng) 的释放. 升高调控的HO-1提供了预防孕前的保护.
科学领域:
- 产科和妇科 产科和妇科
- 心血管研究研究心血管研究
- 分子医学是分子医学.
背景情况:
- 孕前是一种怀孕障碍,其特征是高血压和蛋白尿.
- 高水平的可溶性Flt-1 (sFlt-1) 和可溶性内分泌素 (sEng) 与孕前有关.
- 血氧酶-1 (HO-1) 和其代谢物一氧化碳 (CO) 对氧化应激有保护作用.
研究的目的:
- 通过抑制sFlt-1和sEng释放,调查HO-1上调可以防止孕前的假设.
- 探索HO-1/CO通路在调节sFlt-1和sEng分泌中的作用.
主要方法:
- 过度表达和抑制HO-1在内皮细胞和胎盘小突破体中.
- 在HO-1缺乏小鼠中分析sFlt-1和sEng水平.
- 研究了VEGFR-2在VEGF诱导的sFlt-1释放中的作用.
- 评估了CO释放分子-2 (CORM-2) 和他类药物对HO-1,sFlt-1和sEng的影响.
主要成果:
- 预先缩性小扩展体显示sFlt-1和sEng分泌量增加.
- HO-1过度表达减少了sFlt-1和sEng的释放,而HO-1抑制增加了它们.
- 缺乏HO-1的小鼠表现出较高的sFlt-1和sEng水平.
- 由VEGF诱导的sFlt-1释放依赖于VEGFR-2.
- CORM-2和CO降低了sFlt-1的释放和VEGFR-2的酸化.
- 类药物上调了HO-1并减少了sFlt-1的释放;维生素C和E没有影响.
结论:
- 这种HO-1/CO通路有效地抑制了sFlt-1和sEng.Eng的释放.
- 在怀孕期间,HO-1通过减轻与子宫前相关的因素,起到保护作用.
- HO-1 代表了孕前治疗的潜在治疗标.
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
Regulation of Hematopoietic Stem Cells
3.5K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.5K
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
Role of Hematopoietic Growth Factors
3.9K
Hematopoietic growth factors are molecules that regulate the differentiation rate of hematopoietic stem cells (HSCs). Erythropoietin (EPO), primarily produced by the kidneys, plays a crucial role in erythrocyte production. When oxygen levels in the blood are low, EPO is released into the bloodstream, reaching the bone marrow, where it stimulates HSCs to differentiate and mature into erythrocytes, which are vital for oxygen transport.
Thrombopoietin (TPO), mainly released by the liver,...
Thrombopoietin (TPO), mainly released by the liver,...
3.9K
Oxygen Transport in the Blood
8.3K
Hemoglobin (Hb) is a crucial molecule in the human body, consisting of four polypeptide chains, each bound to an iron-containing heme group. This unique structure enables hemoglobin to bind to oxygen, with each molecule capable of combining with four molecules of oxygen, leading to rapid and reversible oxygen loading. When fully loaded with oxygen, it is called oxyhemoglobin, while hemoglobin that has released oxygen is called reduced hemoglobin or deoxyhemoglobin. As hemoglobin binds oxygen,...
8.3K


