脂肪酸碳对于内皮细胞中dNTP的合成至关重要
Sandra Schoors1,2, Ulrike Bruning1,2, Rindert Missiaen1,2
1Laboratory of Angiogenesis and Neurovascular link, Department of Oncology, University of Leuven, Leuven, B-3000, Belgium.
Nature
|April 2, 2015
概括
内皮细胞需要脂肪酸氧化 (FAO) 才能在血管发芽期间繁殖. 阻止FAO会损害核酸合成,阻碍DNA复制和血管生成.
科学领域:
- 细胞生物学 细胞生物学
- 代谢研究研究 代谢研究
- 血管生物学 血管生物学
背景情况:
- 在血管发芽期间内皮细胞的新陈代谢尚不清楚.
- 脂肪酸氧化 (FAO) 是一种关键的代谢途径,在血管生成中没有明确的作用.
研究的目的:
- 调查卡尼丁棕基转移酶1A (CPT1A) 的作用,这是一个限制速度的粮农组织酶,在内皮细胞代谢和功能中.
- 确定受损粮农组织对内皮细胞增殖,迁移和DNA合成的影响.
主要方法:
- 在人类和小鼠内皮细胞中利用了CPT1A的遗传沉默.
- 采用同位素标记研究来追踪代谢途径.
- 评估了细胞的增殖,迁移和核酸合成.
- 在小鼠模型中研究了CPT1A阻塞对病态眼球血管生成的影响.
主要成果:
- CPT1A的内皮损失损害了内皮细胞的增殖,而不是迁移,导致血管生长缺陷.
- 减少的FAO并没有导致能量耗尽或氧化还原失衡,但影响了de novo核酸合成.
- 脂肪酸碳被纳入克雷布斯循环和核酸前体,支持DNA复制.
- CPT1A沉默耗尽了酸盐和脱氧核酸三酸盐;酸盐或核酸拯救了表型.
- 在小鼠中,CPT1阻塞抑制了病态眼球血管生成.
结论:
- 通过提供DNA复制的核酸前体,CPT1A介导的FAO对于内皮细胞的增殖至关重要.
- 通过CPT1封锁准FAO是一种潜在的治疗策略,可以抑制病理性血管生成.
相关概念视频
Overview of Fatty Acid Metabolism
36.9K
Lipids also are sources of energy that power cellular processes. Like carbohydrates, lipids are composed of carbon, hydrogen, and oxygen, but these atoms are arranged differently. Most lipids are nonpolar and hydrophobic. Major types include fats and oils, waxes, phospholipids, and steroids.
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
36.9K
Bicarbonate-Carbonic Acid Buffer
5.6K
The carbonic acid-bicarbonate buffer system is critical for maintaining the body's pH balance. It operates on the equilibrium:
5.6K
The Carbon Cycle
43.7K
Carbon is the basis of all organic matter on Earth, and is recycled through the ecosystem in two primary processes: one in which carbon is exchanged among living organisms, and one in which carbon is cycled over long periods of time through fossilized organic remains, weathering of rocks, and volcanic activity. Human activities, including increased agricultural practices and the burning of fossil fuels, has greatly affected the balance of the natural carbon cycle.
43.7K
Synthesis and Decomposition Reactions
38.1K
Synthesis and decomposition are two types of redox reactions. Synthesis means to make something, whereas decomposition means to break something. The reactions are accompanied by chemical and energy changes.
38.1K
Compounds Essential to Human Function
10.1K
The human body is composed of cells that are fundamentally made up of several different molecules. These molecules are essential to carry out all physiological processes in the body and are broadly classified into organic and inorganic based on their chemical structures.
Inorganic Compounds Essential to Human Functioning
Inorganic compounds essential to human functioning include water, salts, acids, and bases. These compounds are inorganic, i.e., they do not have a carbon-hydrogen bond. Water...
Inorganic Compounds Essential to Human Functioning
Inorganic compounds essential to human functioning include water, salts, acids, and bases. These compounds are inorganic, i.e., they do not have a carbon-hydrogen bond. Water...
10.1K
Amino acids
105.2K
Amino acids are the monomers that comprise proteins. Each amino acid has the same fundamental structure, which consists of a central carbon atom, or the alpha (α) carbon, bonded to an amino group (NH2), a carboxyl group (COOH), and to a hydrogen atom. Every amino acid also has another atom or group of atoms bonded to the central atom known as the R group. There are 20 common amino acids present in proteins, each with a different R group. Variation in the amino acid sequence is responsible for...
105.2K


