富含氧气的产后环境通过DNA损伤反应诱导心肌细胞循环停止
Bao N Puente1, Wataru Kimura2, Shalini A Muralidhar2
1Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cell
|April 29, 2014
概括
出生后的过渡到氧气触发了心脏细胞 (心肌细胞) 通过活性氧物种的细胞循环停止. 减少氧化压力可能会增强心脏再生疗法.
科学领域:
- 心血管生物学 心血管生物学
- 细胞再生 细胞再生
- 新生儿生理学 新生儿生理学
背景情况:
- 哺乳动物的心脏在出生后具有有限的再生能力.
- 心肌细胞在出生后不久就退出细胞周期,停止增殖.
- 这种永久性细胞循环退出的触发因素在很大程度上是未知的.
研究的目的:
- 为了确定导致心肌细胞细胞循环停止的主要产后事件.
- 调查富含氧气的产后环境作为上游信号的作用.
- 探索将氧气暴露与细胞循环暴露联系在一起的机制.
主要方法:
- 在新生儿心脏中量化反应性氧物种 (ROS) 和氧化性DNA损伤标志物.
- 评估DNA损伤反应 (DDR) 标志物在出生后的第一个星期.
- 实验性操纵氧气水平 (低氧化,高氧化),ROS清理和DDR抑制 in vivo.
主要成果:
- 在产后第一周观察到ROS,氧化DNA损伤和DDR标志物的显著增加.
- 产后低氧症,ROS清除或DDR抑制延长了心肌细胞增殖窗口.
- 高氧化和ROS生成器加速了心肌细胞细胞循环的停止.
结论:
- 过渡到富含氧气的环境是心肌细胞细胞循环停止的关键信号.
- ROS和随后的DNA损伤触发了细胞周期退出的保护机制.
- 减少线粒体依赖的氧化应激对于开发心肌细胞增殖疗法至关重要.
相关概念视频
DNA Damage Can Stall the Cell Cycle
2.4K
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...
2.4K
DNA Damage can Stall the Cell Cycle
8.5K
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...
8.5K
Negative Regulator Molecules
32.1K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
32.1K
The Cell Cycle Control System
5.1K
The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
5.1K
The Cell Cycle Control System
11.9K
The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
11.9K
Mitogens and the Cell Cycle
6.3K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.3K


