索拉和异索拉通过与凯尔奇类ECH相关蛋白1的相互作用激活核因子红色素2-相关因子2
Chengyu Lv1, Song Wang1, Chang Sun1
1Institute of Agro-Food Technology Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China) Changchun China.
Food science & nutrition
|January 27, 2025
概括
在植物中发现的天然抗氧化剂psoralen和isopsoralen通过与Keap1.1.的相互作用来激活Nrf2通路. 这种相互作用增强了细胞防御机制,突出了它们作为食补充剂的潜力.
科学领域:
- 自然产品 化学 化学
- 分子生物学分子生物学
- 细胞信号传输 细胞信号传输
背景情况:
- 松烯和异烯是天然的furocoumarins,可以在像Ficus carica和Psoralea corylifolia这样的植物中找到.
- 这些化合物具有已知的生物活性,包括抗菌和抗炎性质.
- 它们抗氧化活性背后的精确机制,特别是Nrf2通路激活,需要进一步研究.
研究的目的:
- 通过psoralen和isopsoralen研究核因素红色素2相关因子2 (Nrf2) 的激活.
- 探索Kelch-like ECH相关蛋白1 (Keap1) 和这两种furocoumarins之间的结合相互作用.
- 阐明它们抗氧化性质的分子基础.
主要方法:
- 使用HEK293T细胞研究了Nrf2核转位和抗氧化剂反应元素 (ARE) 驱动的光酶活性.
- 使用定量实时PCR (qRT-PCR) 来评估Nrf2目标基因 (GCLM,HO-1,NQO1) 的mRNA表达.
- 进行了分子对接模拟,以分析psoralen和isopsoralen与Keap1蛋白的结合相互作用.
主要成果:
- 素和异素都证明了对HEK293T细胞的Nrf2核转位的剂量依赖诱导.
- 在与这些furocoumarins治疗时观察到ARE驱动的光酶活性的激活.
- 发现了GCLM,HO-1和NQO1基因表达和蛋白质水平的显著上调.
- 分子对接表明psoralen和isopsoralen与Keap1 Kelch域的中央口袋结合.
结论:
- 色素和异色素激活Nrf2信号通路.
- 这些furocoumarins与Keap1相互作用,导致Nrf2激活.
- 这些发现支持psoralen和isopsoralen作为通过Keap1-Nrf2相互作用介导的天然抗氧化剂的作用.
相关概念视频
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
NF-κB-dependent Signaling Pathway
7.2K
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...
7.2K
Nucleotide Excision Repair
3.4K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.4K
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
Transducer Mechanism: Nuclear Receptors
1.3K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.3K
MAPK Signaling Cascades
5.1K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.1K


