酸脱酶对于心脏中的表观遗传和代谢平衡至关重要
Wenwen Li1, Li Quan2, Kun Peng2
1Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China.
Basic research in cardiology
|October 11, 2023
概括
酸脱酶 (SDH) 缺乏会破坏心脏新陈代谢,从脂肪酸氧化转变为糖解. 恢复脂肪酸氧化可以改善小鼠心力衰竭和代谢功能障碍.
科学领域:
- 心血管生物学 心血管生物学
- 代谢调节 代谢调节 代谢调节 代谢调节
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 心力衰竭的特征是从脂肪酸氧化 (FAO) 转向糖解的代谢转变.
- 特定的酶,如糖酸脱酶 (SDH) 在维持这种代谢平衡中的作用至关重要,但尚未完全理解.
研究的目的:
- 研究酸脱酶 (SDH) 在维持心肌代谢平衡中的作用.
- 阐明SDH缺乏导致心力衰竭和代谢失调的机制.
主要方法:
- 产生心肌细胞受限删除SDH子单元b或c的小鼠.
- 评估心脏功能,新陈代谢 (FAO和糖解) 和心脏缩.
- 对全基因组DNA甲基化,酸盐水平和心肌转录特征的分析.
- 干预高脂肪饮食和α-甲酸盐以评估治疗潜力.
主要成果:
- 心肌细胞中SDH缺乏导致扩张性心肌病和心力衰竭.
- 缺少SDH的心脏显示粮农组织的减少,糖解的增加和酸盐水平的升高.
- 在SDH缺乏的心脏中观察到DNA甲基化增加和基因表达改变,这与酸盐积累有关.
- 通过高脂肪饮食恢复FAO,心脏功能得到改善,而α-甲酸盐则使代谢和转录概况正常化.
结论:
- SDH对于维持粮农组织与心脏中的糖解之间的平衡至关重要.
- 由于SDH缺乏,酸盐的积累会导致表观遗传和转录基因的变化,导致心脏功能障碍.
- 向糖酸代谢和表观遗传修饰,为与SDH缺乏相关的心力衰竭提供了潜在的治疗策略.
相关概念视频
01:20Sulfur Assimilation
20
Sulfur is an essential element in biological systems, contributing to synthesizing key biomolecules, including amino acids such as cysteine and methionine, and cofactors such as coenzyme A and biotin. Microorganisms primarily assimilate sulfur as sulfate (SO₄²⁻) from the environment, which must undergo a series of biochemical transformations before it can be incorporated into cellular components. As sulfate is highly oxidized, it must undergo assimilatory sulfate reduction to...
20
02:36The Citric Acid Cycle
151.9K
The citric acid cycle, also known as the Krebs cycle or TCA cycle, consists of several energy-generating reactions that yield one ATP molecule, three NADH molecules, one FADH2 molecule, and two CO2 molecules.
151.9K
01:41The Supercomplexes in the Crista Membrane
2.5K
The mitochondrial cristae membrane is the primary site for the oxidative phosphorylation (OXPHOS) process of energy conversion mediated through respiratory complexes I to V. These complexes have been widely studied for decades, and it has been proven that they form supramolecular structures called respiratory supercomplexes (SC). These higher-order complexes may be crucial in maintaining the biochemical structure and improving the physiological activity of the individual complexes while...
2.5K
01:37Epigenetic Regulation
3.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.0K
01:46Electron Transport Chain: Complex I and II
14.3K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
14.3K
01:27Redox Reactions
20
Redox reactions are vital biochemical processes that underpin energy metabolism in cells. These reactions involve the transfer of electrons between molecules, occurring in tandem as oxidation and reduction. Oxidation refers to the loss of electrons, while reduction denotes their gain. This coupling ensures the seamless flow of electrons through metabolic pathways. For example, in bacterial metabolism, glucose undergoes oxidation to carbon dioxide, while oxygen is simultaneously reduced to...
20