BET蛋白抑制剂JQ1调节了由慢性病引起的线粒体功能障碍和氧化应激
Sandra Rayego-Mateos1,2, Pamela Basantes1,2, José Luis Morgado-Pascual1,3
1Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz-Universidad Autónoma Madrid, 28040 Madrid, Spain.
Antioxidants (Basel, Switzerland)
|May 27, 2023
概括
像JQ1这样的额外终端域蛋白 (iBET) 抑制剂通过改善线粒体功能和减少氧化应激来保护脏疾病. 这些表观遗传药物增强了线粒体动力学,并恢复了细胞中的抗氧化防御.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 线粒体生物学 线粒体生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 线粒体功能障碍是病进展的关键因素.
- 表观遗传药物,特别是额外终端域蛋白 (iBETs) 抑制剂,通过减少炎症和增殖,在管理实验性病方面表现有前途.
研究的目的:
- 在病模型中研究iBETs对线粒体损伤的影响.
- 探索iBETs如何影响线粒体动力学,氧化酸化和氧化应激.
主要方法:
- 在体外研究中,使用受TGF-β1.1.刺激的人类近接管状细胞进行了体外研究.
- 在体内研究使用小鼠单边尿路阻塞 (UUO) 模型.
- 对氧化酸化 (OXPHOS) 成分,线粒体动态蛋白 (DRP-1,OPA-1) 和抗氧化基因表达的评估.
- 测量反应性氧物种 (ROS) 生产.
主要成果:
- 在体外,JQ1阻止了TGF-β1诱导的OXPHOS成分 (细胞染色体C,CV-ATP5a) 的下调.
- 在体外,JQ1抑制了TGF-β1诱导的线粒体裂变因子DRP-1的增加.
- 在UUO模型中,JQ1的使用防止了细胞染色体C和CV-ATP5a的减少,并使DRP1和OPA-1水平正常化,恢复了线粒体动力学.
- 在这两种模型中,JQ1恢复了抗氧化基因表达 (catalase,Heme oxygenase 1) 并降低了ROS的产生.
结论:
- 以JQ1为例的IBETs有效地减轻脏疾病中的线粒体损伤.
- 这些药物改善线粒体动力学,增强功能,减少氧化应激,为病提供潜在的治疗策略.
更多相关视频
08:15Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease
Published on: May 10, 2024
614
07:15Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
489
相关概念视频
01:25Chronic Kidney Disease I: Introduction
48
Chronic Kidney Disease (CKD) arises when the kidneys progressively lose their ability to function, ultimately leading to end-stage renal disease. At this advanced stage, the kidneys can no longer filter waste or maintain essential body functions, requiring renal replacement therapy (RRT) through dialysis or a kidney transplant for survival.Early-stage chronic kidney disease and detection challengesIn CKD's early stages, symptoms often remain absent because healthy nephrons compensate for...
48
01:24Chronic Kidney Disease II: Clinical Manifestations
46
Chronic Kidney Disease (CKD) progressively impairs multiple body systems due to the accumulation of uremic toxins, which disrupt cellular functions across various organs.Neurologic symptomsNeurologic symptoms often arise early in CKD, as uremic toxin buildup drives changes in cognitive and motor functions. Patients frequently experience fatigue, headache, confusion, difficulty concentrating, and, in severe cases, seizures. Peripheral neuropathy commonly manifests as burning sensations in the...
46
01:18Chronic Kidney Disease IV: Nursing Management
29
Nursing management is essential for preventing complications, maintaining stability, and improving patients' quality of life in chronic kidney disease (CKD). By using a structured approach, nurses help slow CKD progression and support effective patient care.1. Comprehensive patient assessmentEffective management begins with nurses reviewing the patient’s medical history, and identifying key risk factors like diabetes, hypertension, and nephrotoxic drug use. Nurses assess signs of...
29
01:29Acute Kidney Injury II: Pathophysiology
37
Acute kidney injury (AKI) causes are categorized into three primary categories based on the location of the injury: prerenal, intrarenal (or intrinsic), and postrenal causes. This classification guides clinical management and illustrates how different pathways can impair kidney function.Etiology and Pathophysiology of Acute Kidney Injury1. Prerenal causesEtiology: Prerenal Acute Kidney Injury, the most common type, occurs when reduced blood flow to the kidneys decreases filtration capacity...
37
01:28Chronic Kidney Disease III: Interprofessional Care
51
Chronic kidney disease (CKD) requires collaborative and comprehensive management. CKD progresses through stages and can lead to end-stage kidney disease (ESKD) if untreated. Interprofessional collaboration and patient education are crucial, enabling patients to manage their health and improve their quality of life.Diagnostic approach for chronic kidney diseaseThe diagnosis of CKD primarily focuses on the glomerular filtration rate (GFR), which assesses kidney function by measuring how well...
51
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
41
Accurate diagnosis and effective prevention are critical in managing Acute Kidney Injury (AKI), which is linked to high mortality rates ranging from 10% to 80%. Timely recognition of at-risk patients and careful monitoring can significantly reduce the likelihood of kidney damage.Diagnostic Assessments:The diagnostic process starts with a comprehensive medical history to identify prerenal, intrarenal, and postrenal causes.Prerenal causes, such as dehydration, hypotension, or blood loss, should...
41