肝核因子 红状腺 2 相关因子 1 活动促进宿主防御在内毒性和细菌性败血症
Michael J Trites1, Lei Li1, Uche Njoku1
1Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
概括
肝脏中核因子红色素2相关因子-1 (Nrf1) 活性受损会使败血症和内毒性结局恶化. 增强Nrf1活动可以增强肝脏的防御能力,改善存活率并预防败血症期间的低温.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 败血症和内毒性导致器官损伤和死亡.
- 肝脏使用代谢适应来控制压力和损伤.
- 细胞和系统应激防御编程协调肝脏的防御.
研究的目的:
- 研究核因子红色素2相关因子-1 (Nrf1) 和-2 (Nrf2) 在肝细胞内毒性和败血症期间的作用.
- 确定Nrf1和Nrf2是否可以预防败血症引起的肝损伤和死亡.
主要方法:
- 在小鼠中进行了内毒症 (脂多糖) 或败血症 (大肠杆菌) 的检查.
- 肝脏Nrf1和Nrf2活性是基因调节的.
- 评估了生存时间,体温,细胞因子水平,肝炎,基因/蛋白质表达和肝脏代谢.
主要成果:
- 肝脏Nrf1和Nrf2活性在内毒性和败血症下降.
- Nrf1缺乏,而不是 Nrf2,导致低温和增加死亡率.
- 增加的Nrf1活性通过增强非常低密度脂蛋白 (VLDL) 分泌和甘油三代谢,改善了生存率和减轻了低温.
结论:
- 肝脏Nrf1活性受损会加剧内毒性病和败血症中的死亡率.
- 增加肝脏Nrf1活性的干预措施可以促进肝脏防御,防止与败血症相关的低温和死亡率.
相关概念视频
NF-κB-dependent Signaling Pathway
7.9K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.9K
Role of Hematopoietic Growth Factors
1.7K
Hematopoietic growth factors are molecules that regulate the differentiation rate of hematopoietic stem cells (HSCs). Erythropoietin (EPO), primarily produced by the kidneys, plays a crucial role in erythrocyte production. When oxygen levels in the blood are low, EPO is released into the bloodstream, reaching the bone marrow, where it stimulates HSCs to differentiate and mature into erythrocytes, which are vital for oxygen transport.
Thrombopoietin (TPO), mainly released by the liver,...
Thrombopoietin (TPO), mainly released by the liver,...
1.7K
Stringent Response in E. coli
62
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
62
Regulation of the Unfolded Protein Response
2.6K
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...
2.6K
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Inflammatory Response
8.6K
An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
8.6K


