塞达诺利德激活KEAP1-NRF2通路并改善过氧化诱导的细胞死亡
Yosuke Tabei1, Hiroko Abe1, Shingo Suzuki1,2
1Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 2217-14 Hayashi-cho, Takamatsu 761-0395, Kagawa, Japan.
International journal of molecular sciences
|November 25, 2023
概括
塞达诺利德通过激活凯尔奇样ECH相关蛋白1 (KEAP1) -核因子E2相关因子2 (NRF2) 途径来增强细胞对氧化应激的抵抗力. 这种化合物可以保护肝细胞免受过氧化引起的损伤.
科学领域:
- 生物化学 生物化学
- 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:
- 塞达诺利德是一种生物活性化合物,具有已知的抗炎和抗瘤特性.
- 已经提出了sedanolide激活核因子E2相关因子2 (NRF2) 途径的建议,但其在氧化应激抵抗中的作用尚未得到充分研究.
- 氧化应激有助于各种病理,使得识别可减轻其影响的化合物至关重要.
研究的目的:
- 为了研究氧化 (H2O2) 诱导的氧化损伤对人类肝细胞母细胞瘤 HepG2 细胞的sedanolide 的保护作用.
- 阐明基因作用的分子机制,特别是其对NRF2路径的影响.
- 评估sedanolide作为治疗氧化应激相关细胞损伤的治疗剂的潜力.
主要方法:
- 使用的HepG2细胞暴露于H2O2以诱导氧化应激.
- 进行了类的预治疗,以评估其保护作用.
- 通过核转位和抗氧化剂反应元素 (ARE) 活性分析了NRF2通路的激活.
- 进行RNA测序以识别受影响的细胞通路和基因表达.
- 测量了反应性氧物种 (ROS) 生成,线粒体膜潜力和caspase-3/7活性.
主要成果:
- 塞达诺利德通过NRF2核转位激活了ARE依赖转录.
- RNA测序揭示了抗氧化酶和谷氨代谢基因的上调.
- 赛达诺利德显著降低了H2O2诱导的细胞和线粒体ROS产量.
- 预先用西达诺利德治疗可以防止线粒体膜潜力的下降和卡斯巴-3/7活性的增加.
- 塞达诺利德对H2O2诱导的细胞死亡有显著的细胞保护作用.
结论:
- 塞达诺利德通过激活KEAP1-NRF2通路来增强细胞对氧化损伤的抵抗力.
- 塞达诺利德通过降低ROS水平和保持线粒体功能来减轻H2O2诱导的细胞损伤.
- 这些发现凸显了sedanolide在对抗氧化压力相关疾病方面的潜在治疗价值.
相关概念视频
01:24Peroxisomes
13.1K
Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
13.1K
02:44Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide
10.3K
Alkenes are converted to 1,2-diols or glycols through a process called dihydroxylation. It involves the addition of two hydroxyl groups across the double bond with two different stereochemical approaches, namely anti and syn. Dihydroxylation using osmium tetroxide progresses with syn stereochemistry.
10.3K
01:46Electron Transport Chain: Complex I and II
14.0K
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...
14.0K
01:17The Extrinsic Apoptotic Pathway
6.4K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.4K