通过IRP1调节铁平衡,改善了血管光滑肌肉细胞功能
Jiechun Zhu1, Yuehong Wang1, Alexis Rivett1
1School of Natural Sciences, Laurentian University, Sudbury, Canada; Cardiovascular and Metabolic Research Unit, Laurentian University, Sudbury, Canada.
Cellular signalling
|July 24, 2023
概括
硫化 (H2S) 和铁代谢对心血管健康至关重要. 这项研究揭示了它们在血管光滑肌肉细胞中的复杂相互作用,确定了氨酸马酶 (CSE) /H2S系统作为与铁失调相关的血管疾病的潜在治疗标.
科学领域:
- 生物化学 生物化学
- 心血管生物学 心血管生物学
- 细胞的新陈代谢
背景情况:
- 硫化 (H2S) 和铁对细胞功能至关重要,与心血管疾病风险相关的异常代谢.
- 血管光滑肌细胞 (SMC) 功能对血管健康至关重要,其由细胞代谢物调节是积极研究的领域.
研究的目的:
- 研究铁和H2S信号通路在调节血管SMC功能的相互相互作用.
- 探索囊氨酸马酶 (CSE) /H2S系统在血管组织内的细胞铁稳态中的作用.
主要方法:
- 利用安吉奥素II注入的小鼠模型在体内评估大动脉铁积累.
- 在铁过载和饥饿的体外研究中使用CSE淘汰 (KO) 和野生型 (WT) 鼠标衍生的SMC.
- 分析了细胞增殖,F-actin完整性,SMC特异性标记物表达和铁调节蛋白1 (IRP1) 活性.
主要成果:
- CSE缺乏症加剧了铁积累和不良的SMC表型变化,而H2S的使用减轻了这些影响.
- 与WT-SMC相比,KO-SMCs对铁过载和饥饿诱导的细胞死亡的脆弱性增加.
- H2S调节IRP1活动,影响费里和费里波水平,从而调节细胞内可变铁. 铁抑制了CSE衍生的H2S,但诱导了从氨酸中非酶的H2S释放.
结论:
- 在血管SMC中铁和H2S信号之间存在显著的相互相互作用,影响细胞功能和表型.
- CSE/H2S通路对血管组织中铁失调起着保护作用.
- 针对CSE/H2S系统为与铁代谢障碍相关的血管疾病提供了潜在的治疗策略.
相关概念视频
Regulation of Angiogenesis and Blood Supply
2.6K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
Autoregulation of Blood Flow
2.4K
Autoregulation mechanisms are characterized by their inherent capacity for self-regulation without necessitating specific nervous stimulation or endocrine control. These mechanisms facilitate the adjustment of blood flow and, therefore, perfusion specific to each tissue region. This self-regulation encompasses chemical signals and myogenic controls.
Chemical Signaling in Autoregulation
Chemical signaling operates at the precapillary sphincter level, inciting either contraction or relaxation....
Chemical Signaling in Autoregulation
Chemical signaling operates at the precapillary sphincter level, inciting either contraction or relaxation....
2.4K
Regulation of the Unfolded Protein Response
2.5K
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...
2.5K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.2K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
Regulation of Hematopoietic Stem Cells
3.2K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.2K
Sulfur Assimilation
45
Sulfur is an essential element in biological systems, contributing to synthesizing key biomolecules, including amino acids such as cysteine and methionine, and cofactors such as coenzyme A and biotin. Microorganisms primarily assimilate sulfur as sulfate (SO₄²⁻) from the environment, which must undergo a series of biochemical transformations before it can be incorporated into cellular components. As sulfate is highly oxidized, it must undergo assimilatory sulfate reduction to...
45


