核因子红色素2相关的因子-1是通过营养药物CELASTROL在蛋白质酶抑制剂量刺激的
Alireza Ahadiabhari1, Lei Li1, Shennan Su1
1Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Biochemical and biophysical research communications
|June 13, 2025
概括
塞拉斯托尔通过抑制蛋白酶体活性来刺激压力保护因子核因子红色素2相关因子1 (NRF1). 然而,塞拉斯特罗尔
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 许多营养药的健康益处尚未完全理解,其中一些通过蛋白质酶抑制作用.
- 核因子红色素2相关因子1 (NRF1) 是一种转录因子,由抑制的蛋白酶体活性激活.
研究的目的:
- 调查具有蛋白质酶抑制性质的营养药是否可以刺激NRF1.
- 为了确定一种营养药物化合物塞拉斯特是否激活NRF1并调节压力保护基因.
主要方法:
- 在Hepa 1-6细胞中使用基于光酶的记者测定来选NRF1和NRF2活性的营养品.
- 采用野生类型和Nrf1缺乏的小鼠胚胎纤维细胞和Hep3B细胞来评估的作用.
- 测量了蛋白酶体活性和NRF1处理,核积累和下游基因调节.
主要成果:
- 塞拉斯托尔在2和4μM的剂量强烈刺激了Hepa 1-6细胞中的NRF1活性.
- 在小鼠胚胎纤维细胞中,Nrf1缺乏减弱了醇诱导的记者活性.
- 塞拉斯托尔 (2μM) 增加了Hep3B细胞中的NRF1处理和核积累,抑制了蛋白酶体活性.
- 与MG132和博特佐米布等蛋白质酶体抑制剂相比,塞拉斯显示出明显的NRF1依赖基因调节.
结论:
- 塞拉斯在度上刺激NRF1,抑制蛋白酶体活性.
- 塞拉斯特对压力保护基因的调节与传统的蛋白酶体抑制剂不同.
- NRF1可能会调解醇和其他蛋白酶体抑制营养品的一些健康益处.
更多相关视频
08:49Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
9.1K
06:00Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
Published on: May 14, 2016
11.0K
相关概念视频
01:45Regulation 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
02:38Mitogens and the Cell Cycle
6.4K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.4K
01:23Negative Regulator Molecules
35.2K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.2K
01:31Transducer 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
02:26NF-κB-dependent Signaling Pathway
7.4K
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...
7.4K
01:23Regulation of Expression at Multiple Steps
875
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
875