赛尔图因调节剂减轻缺氧诱导的细胞死亡,原因是基因素3乙化变化,以及线粒体功能,动态和内容的变化
Luiz Felipe Souza E Silva1, Amanda Siena2, Jessica Mayumi Yuzawa3
1Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil; Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Neuropharmacology
|May 2, 2025
概括
赛尔图因调节剂通过减少活性氧物种和改善细胞代谢来保护神经元免受低氧诱导的线粒体损伤和细胞死亡,为神经发育障碍提供潜在的治疗方法.
科学领域:
- 神经科学是一个神经科学.
- 线粒体生物学 线粒体生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 缺氧是一个重要的环境因素,导致神经发育并发症,通常是通过线粒体功能障碍.
- 赛尔图因在调节细胞和线粒体新陈代谢方面发挥着至关重要的作用,使他们成为治疗干预的潜在目标.
研究的目的:
- 调查sirtuins的药理调制是否可以保护神经元免受低氧诱导的线粒体功能障碍和细胞死亡.
- 探索Sirtuin调节器在神经发育障碍中的治疗潜力.
主要方法:
- 来自Wistar和自发高血压大鼠的原发皮质神经元被暴露在化中以诱导化学缺氧.
- 用Sirtuin调节剂 (尼古丁胺,白醇,Sirtinol) 治疗神经元,以评估它们的保护作用.
- 评估的参数包括细胞活力,线粒体功能 (膜潜力,保留),活性氧物种 (ROS) 水平,基因表达 (线粒体代谢,动态,生物发生) 和高能化合物.
主要成果:
- 缺氧诱导了线粒体脱极化,减少了保留,增加了ROS,以及与线粒体生物发生和裂变相关的基因表达变化,以及ATP降低和高铁酸盐/乳酸盐水平.
- 赛尔图因调节剂显著提高了神经元活力,减少了ROS产量,并改善了线粒体功能.
- 治疗使酸盐和乳酸盐的产生正常化,增加了ATP水平,并调节了线粒体融合基因表达.
结论:
- 赛尔图因调节剂有效地减轻缺氧诱导的神经元损伤和线粒体功能障碍.
- 这些发现表明,Sirtuin调节器作为与缺氧相关的神经发育障碍的治疗策略具有前途.
相关概念视频
01:45Mitochondrial Membranes
6.6K
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,...
6.6K
01:31Regulation of the Unfolded Protein Response
2.3K
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...
2.3K
01:46Electron Transport Chain: Complex I and II
9.6K
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...
9.6K
01:37Mitochondria
8.9K
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,...
8.9K
01:24Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
01:22PI3K/mTOR/AKT Signaling Pathway
3.3K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.3K