相关实验视频
Updated: Jul 14, 2026

08:51
A New Murine Model of Endovascular Aortic Aneurysm Repair
Published on: July 7, 2013
14.3K
乌比奎丁类修饰剂激活酶1作为大动脉剖析的潜在治疗点
Yao Wang1, Jinjin Zhang1, Yunsong Wang2
1Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
International immunopharmacology
|December 5, 2024
概括
研究人员发现,E1酶UBA1 (基类修饰激活酶1) 在大动脉剖析进展中起着关键作用. 用TAK-243抑制UBA1显示出作为这种危及生命的疾病的潜在治疗方法的希望.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 心血管研究研究心血管研究
背景情况:
- 大动脉解剖 (AD) 是一种严重的动脉损伤,缺乏向的药理疗法.
- 关键的细胞过程 - - 乌比基化 (ubiquitination) 涉及到AD的发病过程,但E1酶的作用尚不清楚.
研究的目的:
- 调查E1酶,特别是泛胺类修饰激活酶1 (UBA1) 在大动脉剖析进展中的作用.
- 在AD的小鼠模型中评估UBA1抑制的治疗潜力.
主要方法:
- 对人类大动脉剖析的转录数据的分析 (GSE52093).
- 在使用免疫组织化学和RT-qPCR的β-aminopropionitrile (BAPN) 诱导的小鼠AD模型中进行验证.
- 使用TAK-243.3进行UBA1的药理抑制.
- 在体外研究中使用血管素II (AngII) 刺激的巨细胞 (RAW264.7细胞).
主要成果:
- 在人类AD和小鼠AD模型中,UBA1被确定为显著上调.
- TAK-243治疗可以预防AD的形成,减少大动脉中枢退化,弹性质碎片化和血管光滑肌肉细胞损失.
- 在体外,TAK-243减弱了巨细胞的积累和激活,减少了促炎性细胞因子的表达,并抑制了NF-κB信号传递.
- 通过抑制MMP2和MMP9的表达,UBA1抑制减少了细胞外矩阵的降解.
结论:
- UBA1促进了大动脉剖析的进展,可能是通过通过NF-κB通路促进巨细胞激活.
- 用像TAK-243这样的抑制剂向UBA1代表了大动脉剖析的有前途的治疗策略.
相关概念视频
Regulated Protein Degradation
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
The Unfolded Protein Response
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
Allosteric Proteins-ATCase
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 pathway,...
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 pathway,...
Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
Transducer Mechanism: Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
Aneurysm I: Introduction
An aortic aneurysm is a localized outpouching or dilation at a weak point in the artery wall. It may involve different parts of the aorta, such as the abdominal aorta, aortic arch, or thoracic aorta.Etiological factorsSeveral disorders are associated with aortic aneurysms.Congenital causes, such as primary connective tissue disorders like Marfan syndrome, impact the integrity and strength of connective tissues, notably affecting the aorta. Marfan syndrome is a genetic disorder that specifically...

