心肌细胞中的DNA损伤相关蛋白共同表达网络提供了对遗传变异和疾病耐受性的信息
Omar Darrel Johnson1,2, Sayan Paul3, José Angel Gutiérrez3
1Biochemistry, Cellular and Molecular Biology Graduate Program, University of Texas Medical Branch, Galveston, TX 77555, USA.
iScience
|June 5, 2025
概括
心血管疾病风险因素导致的DNA损伤会影响心脏细胞蛋白质. 这项研究揭示了DNA损伤如何影响蛋白质网络并影响遗传变异耐受性,为心脏病机制提供了洞察力.
科学领域:
- 心脏病学 心脏病学
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 心血管疾病 (CVD) 由遗传和环境因素引起,通常导致DNA受损.
- DNA 损伤是多种心血管疾病风险因素的结果.
- 了解心肌细胞蛋白质对DNA损伤的反应对心血管疾病研究至关重要.
研究的目的:
- 研究DNA损伤如何影响心肌细胞蛋白质组.
- 探索DNA损伤引起的蛋白质变化与心血管疾病风险之间的关系.
- 为了分析蛋白质网络的动态,以应对DNA损伤.
主要方法:
- 人类诱导多能干细胞 (iPSC) 衍生的心肌细胞被用DNA损伤剂多克索鲁比 (DOX) 治疗.
- 从4178种蛋白质构建了一个蛋白质-蛋白质相互作用网络.
- 与DOX治疗相关的同表达模块和枢纽蛋白被确定并分析.
主要成果:
- 确定了12个共同表达的模块和403个枢纽蛋白. 五个模块与DOX治疗相关,与RNA处理,染色体调节和新陈代谢有关.
- 与DOX相关的枢纽蛋白因遗传因素而显示出较少的变异,但富含功能丧失不耐受基因.
- 这些蛋白质被丰富为已知的心血管疾病风险蛋白的物理相互作用者,但不是已知的心血管疾病风险蛋白本身.
结论:
- 与DNA损伤相关的模块内的蛋白质连接性会影响对遗传变异的耐受性.
- 动态网络分析可以揭示诸如心血管疾病等复杂特征的洞察力.
- 这些发现突出了DNA损伤,蛋白质组网络和心血管疾病的遗传易感性之间的复杂相互作用.
相关概念视频
02:26Protein Networks
4.6K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
4.6K
02:36DNA Damage can Stall the Cell Cycle
10.3K
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...
10.3K
02:36DNA Damage Can Stall the Cell Cycle
3.3K
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...
3.3K
01:30Cardiomyopathy II: Dilated Cardiomyopathy
687
Dilated cardiomyopathy, or DCM, is a progressive myocardial disorder characterized by ventricular chamber dilation and contractile dysfunction.EtiologyVarious factors can cause DCM, including hypertension and heavy alcohol intake, which contribute to the weakening and enlargement of the heart muscle. Viral infections, such as Coxsackievirus B, adenoviruses, and influenza, can lead to DCM by causing inflammation and damage to heart tissue. Certain chemotherapeutic agents, including daunorubicin,...
687