心力衰竭患者的HACE1表达可能通过向NRF2促进线粒体氧化应激和铁亡
Peiyi Yin1, Yongbin Wu1, Xiang Long1
1Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Aging
|December 9, 2023
概括
心力衰竭患者显示HACE1基因表达减少. 升级HACE1可以保护心脏纤维化和氧化应激,为心力衰竭提供潜在的治疗点.
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 是一个遗传学.
背景情况:
- 心力衰竭是一种常见的,严重的疾病,与心房电活动异常和中风风险增加有关.
- 由氧化应激和结构变化驱动的心房重塑是心力衰竭进展的关键.
- 调节基因HACE1 (HECT和RLD域含有E3乌比基因蛋白联酶1) 显示出保护心脏免受心力衰竭的潜力.
研究的目的:
- 为了研究HACE1在心力衰竭病原发生中的作用.
- 探索HACE1作为治疗标和心力衰竭诊断标记物的潜力.
主要方法:
- 对临床心力衰竭患者数据和C57BL/6J小鼠模型的分析.
- 基因和蛋白质表达分析使用RT-PCR,微阵列,ELISA和西方斑点.
- 评估氧化应激,纤维化,铁化和心脏功能,包括对小鼠心房纤维细胞的体外研究.
主要成果:
- 心力衰竭患者的HACE1表达减少,与较高的原水平相关.
- 在小鼠模型中,增加HACE1表达减少了氧化应激,纤维化,并改善了心脏功能.
- HACE1 knockdown 恶化了氧化应激,纤维化和心脏功能障碍;HACE1 受到铁和线粒体损伤的保护,部分是通过NRF2 无处不在.
结论:
- HACE1是一种潜在的治疗标和心力衰竭的诊断标记.
- HACE1可以缓解心脏纤维化,氧化应激,铁亡和线粒体损伤.
- HACE1至少部分通过通过无处不在激活NRF2激活产生保护作用,揭示了心力衰竭中的新机制.
更多相关视频
04:01Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
1.0K
11:26Analyzing Oxygen Consumption Rate in Primary Cultured Mouse Neonatal Cardiomyocytes Using an Extracellular Flux Analyzer
Published on: February 13, 2019
8.8K
相关概念视频
Necrosis
4.5K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.5K
Electron Transport Chain: Complex I and II
13.8K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
13.8K
Mitochondria
13.1K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
13.1K
Pathophysiology of Heart Failure
1.6K
Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. The...
1.6K
The Electron Transport Chain
16.8K
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
16.8K
Mitochondrial Membranes
10.9K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
10.9K
