雅克抑制剂改善了类风湿性关节炎中的ATP产生和线粒体功能:试点研究
Valentina Mihaylova1,2, Maria Kazakova3,4, Zguro Batalov5,6
1Department of Medical Biology, Medical University-Plovdiv, Plovdiv, Bulgaria. valentina.mihaylova@mu-plovdiv.bg.
Rheumatology international
|November 20, 2023
概括
雅克抑制剂可以改善类风湿性关节炎 (RA) 患者的细胞代谢和线粒体功能. 这种疗法增强了ATP的产生,并减少了质子泄漏,与RA的改善临床结果相关.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 类风湿性关节炎 (RA) 是一种慢性自身免疫性疾病,其特征是结膜炎和自身抗体的产生.
- 氧化应激会导致RA的关节和软骨损伤,经常观察到线粒体功能障碍.
- 有限的研究已经探索了RA治疗对细胞能量代谢和线粒体动态的影响.
研究的目的:
- 研究Janus激酶 (JAK) 抑制剂对类风湿性关节炎患者细胞代谢和线粒体功能的直接影响.
- 在诱导氧化应激条件下评估能量参数的变化.
- 为了将代谢和线粒体变化与JAK抑制剂治疗后的临床改善相关联.
主要方法:
- 周围血液单核细胞 (PBMC) 和血从10名新诊断的RA患者中在JAK抑制剂治疗6个月之前和之后收集.
- 使用实时代谢分析来评估PBMC中的线粒体功能和细胞代谢.
- 临床评估包括超声波检查,DAS28分数和常规实验室参数.
主要成果:
- 采用JAK抑制剂治疗导致PBMC中的质子泄漏显著减少.
- 观察到腺三酸盐 (ATP) 产量的显著增加,表明细胞生物能增强.
- 这些代谢改善与临床和超声波参数的改善相关.
结论:
- 雅克抑制剂可能对氧化酸化产生催化作用,从而改善RA中的细胞能量代谢.
- 这项研究提供了第一个体内证据,证明了RA患者中线粒体参数的动态变化,这些患者接受了JAK抑制剂治疗.
- 这些发现表明,JAK抑制剂介导的代谢改善与类风湿性关节炎治疗疗效之间存在直接联系.
相关概念视频
ATP Synthase: Mechanism
14.7K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
14.7K
Electron Transport Chain: Complex I and II
14.1K
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...
14.1K
The JAK-STAT Signaling Pathway
8.9K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.9K
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
436
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
436
Antihypertensive Drugs: Direct Renin Inhibitors
640
The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
640
The Electron Transport Chain
16.8K
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
16.8K


