相关实验视频

Updated: Jun 12, 2025

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro

Published on: February 15, 2022

在一次性血管光滑肌细胞中,CX-5461诱导的DNA损伤反应的分子基础

Tengfei Liu^1,2, Guopin Pan³, Jing Zhang⁴

¹Department of Pharmacology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China.

|September 19, 2024

概括

RNA聚合酶I抑制剂CX-5461在血管细胞中触发DNA损伤反应 (DDR),主要是通过复制应激,而不是双链断裂. 这表明了治疗血管疾病的新机制.

科学领域:

分子生物学分子生物学
细胞生物学细胞生物学
药理学药理学是指药理学的学科.

背景情况:

以前的研究表明,CX-5461通过DNA损伤反应 (DDR) 抑制了血管光滑肌肉细胞的增殖.
在血管细胞中CX-5461诱导的DDR的精确分子机制尚不清楚.
关于CX-5461对癌症和不朽细胞的DDR影响的现有数据是相互矛盾的.

研究的目的:

在初级大动脉光滑肌细胞中研究CX-5461诱导的DDR的分子机制.
为了确定CX-5461治疗激活或不受影响的特定DDR通路.
阐明导致血管细胞中CX-5461激活DDR的主要分子事件.

主要方法:

用CX-5461治疗小鼠主动脉光滑肌细胞.
对各种DNA损伤反应途径 (NER,MMR,NHEJ,HR) 的分析.
使用性彗星测定对DNA双链断裂的评估.
研究复制应激,G-四重复,R-循环和复制-转录冲突.
核和外核DDR的评估,以及Rad51的表达.

主要成果:

在血管细胞中,CX-5461诱导了DDR,激活了同类重组,但不是NER,MMR或NHEJ.
没有发现显著的DNA双链断裂;DDR与复制压力有关.
复制压力归因于复制-转录冲突,而不是G-四重复或R-循环形成.
观察到核外DDR和下调的Rad51表达.

结论:

DNA复制压力是触发ATM/ATR和p53激活的首要事件,在CX-5461治疗的血管光滑肌细胞中.
血管细胞中CX-5461诱导的DDR主要通过复制-转录冲突进行调解.
这些发现提供了关于CX-5461在增殖性血管疾病中的潜在治疗效果的见解.

关键词:

在ATM/ATR中使用.在CX-5461中使用.对DNA损伤的反应反应原子核的核心是什么?复制应激是复制应激的一种.血管光滑肌肉细胞细胞在p53中,p53是什么?

更多相关视频

Murine Aortic Crush Injury: An Efficient In Vivo Model of Smooth Muscle Cell Proliferation and Endothelial Function

Murine Aortic Crush Injury: An Efficient In Vivo Model of Smooth Muscle Cell Proliferation and Endothelial Function

Published on: June 11, 2017

Perturbing Endothelial Biomechanics via Connexin 43 Structural Disruption

Perturbing Endothelial Biomechanics via Connexin 43 Structural Disruption

Published on: October 4, 2019

相关概念视频

DNA Damage can Stall the Cell Cycle

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...

Nucleotide Excision Repair

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...

Vascular Spasm

Vascular Spasm

The vascular phase, also known as vasospasm, is the initial stage of hemostasis, crucial for preventing excessive bleeding when a blood vessel is injured. After a vessel is cut, nerves in the damaged area trigger pain and other sensory impulses. Simultaneously, the smooth muscles in the vessel wall contract, resulting in a vascular spasm. This contraction reduces the vessel's diameter at the injury site, slowing or stopping blood loss through the vessel wall. Vascular spasms typically last...