适度升高的homocysteine通过适应性UPR激活和代谢重新连接诱导内皮功能障碍
Barun Chatterjee1,2, Fabeha Fatima1, Surabhi Seth1,2
1CSIR-Institute of Genomics & Integrative Biology, New Delhi 110025, India.
Cells
|February 9, 2024
概括
适度升高的homocysteine (Hcy) 通过损害细胞迁移和增殖导致内皮功能障碍. 这涉及次致命的ER压力和代谢变化,为心血管健康提供潜在的治疗点.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 心血管科学 心血管科学
背景情况:
- 过高homocysteinemia (HHcy),高水平的homocysteine (Hcy),与心血管疾病有关.
- 严重的HHcy通过内皮细胞死亡引起血管病理.
- 中度HHcy在内皮生理学的作用在很大程度上是未知的.
研究的目的:
- 为了研究中度HHcy对内皮细胞功能的影响.
- 阐明中度HHcy诱导的内皮功能障碍背后的分子机制.
主要方法:
- 细胞培养研究中度Hcy升高.
- 对内皮细胞迁移,增殖,基因表达 (VEGF/VEGFR),ROS产生,ER压力标志物,actin细胞骨架,线粒体呼吸和糖解的分析.
- 微阵列数据集的生物信息分析.
主要成果:
- 适度的Hcy会影响内皮细胞迁移和增殖,但不会影响VEGF/VEGFR或诱导ROS.
- 亚致死的ER压力和异常的actin重塑有助于缺陷迁移.
- 线粒体呼吸被抑制,糖分分解增加,导致ATP损失和能量恒温.
- 这些发现被保留在成年内皮细胞中.
结论:
- 适度的HHcy通过自适应的未折叠蛋白质反应 (UPR) 和代谢重新连接诱导内皮功能障碍.
- 这些机械路径代表了调节内皮功能和心血管健康的潜在目标.
相关概念视频
Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
92
Cardiac biomarkers are critical in diagnosing, prognosing, and managing cardiovascular diseases. Routine measurement of specific biomarkers such as B-type natriuretic peptide (BNP), C-reactive protein (CRP), and homocysteine (Hcy) is common practice in clinical settings to evaluate heart function and predict cardiovascular events.
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
92
The Unfolded Protein Response
4.6K
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...
4.6K
Regulation of the Unfolded Protein Response
2.4K
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...
2.4K


