相关实验视频
Updated: May 16, 2025
06:59
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
36.8K
阿斯巴拉金内酶分裂阿波利波蛋白A1并加速动脉样硬化病变的发生
Mengmeng Wang1, Bowei Li2, Shuke Nie1,3
1Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.
The Journal of clinical investigation
|May 15, 2025
概括
阿斯巴拉金内酸酶 (AEP) 通过降解阿波利波蛋白A1 (APOA1) 加快动脉样硬化,从而降低胆固醇流量. 抑制AEP可以减少动脉样硬化的发展,从而成为潜在的治疗点.
科学领域:
- 生物化学 生物化学
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
背景情况:
- 动脉样硬化是一种炎症性疾病,其标志是胆固醇的积累和斑块的形成.
- 阿斯帕拉金内酶 (AEP),一种酸激活蛋白酶,在动脉样硬化患者中升高.
- 在胆固醇代谢和动脉样硬化进展中AEP的确切作用尚未完全理解.
研究的目的:
- 确定参与动脉样硬化斑块发展的关键AEP基质.
- 阐明AEP在破坏胆固醇代谢中的机制.
- 为新型动脉样硬化疗法奠定基础.
主要方法:
- 在人类动脉样硬化斑块和APOE-null小鼠模型中评估了AEP水平.
- 研究了AEP对阿波利波蛋白A1 (APOA1) 裂变和胆固醇流失的影响.
- 利用遗传 (N208A突变) 和药理 (抑制剂#11a) 方法阻止APOE-null和LDLR-null小鼠中的AEP活性.
主要成果:
- 在人类的动脉样硬化斑块中,AEP升高,并且在APOE-null小鼠的肝脏和大动脉中被激活.
- AEP直接在N208切割APOA1,从而影响高密度脂蛋白 (HDL) 的形成和胆固醇流出.
- 删除AEP或阻断APOA1裂变可显著减轻小鼠模型中的动脉样硬化.
结论:
- 通过降解APOA1,AEP破坏胆固醇代谢,从而加速动脉样硬化.
- 针对AEP或其与APOA1的相互作用,为动脉样硬化提供了一个有希望的治疗策略.
更多相关视频
相关概念视频
01:38Inflammation
51.8K
Overview
51.8K
01:24Caspases
11.5K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
11.5K
01:02Protein Digestion
101.0K
Protein digestion begins in the stomach, where the highly acidic environment can easily disrupt protein structure by exposing the peptide bonds of polypeptide chains. After polypeptide chains are broken into individual amino acids by a series of digestive enzymes, the amino acids are transported to the liver via the bloodstream to produce energy.
101.0K
01:25cAMP-dependent Protein Kinase Pathways
6.0K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.0K
01:19Allosteric Proteins-ATCase
5.6K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.6K
01:39Receptor-mediated Endocytosis
103.6K
Overview
103.6K