相关实验视频

Updated: May 27, 2025

A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish

A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish

Published on: June 7, 2018

希斯蒂丁三核酸结合蛋白2通过恢复 lysosomal 功能和促进小鼠的自减弱多克索鲁比诱导的心脏毒性

Hao Jiang^1,2,3,4,5, Jinyan Zhang^1,3,4,5, Daile Jia^1,2,3,4,5

¹Department of Cardiology Zhongshan Hospital Fudan University Shanghai Institute of Cardiovascular Diseases Shanghai Shanghai China.

|February 19, 2025

概括

胺三核酸结合蛋白2 (HINT2) 保护心脏免受化疗药物多克索鲁比 (DOX) 引起的心脏毒性. 增强HINT2或补充尼古丁胺单核酸 (NMN) 可能会预防心脏损伤.

科学领域:

心脏病学心脏病学
分子生物学分子生物学
生物化学生物化学

背景情况:

多克索鲁比 (DOX) 是一种具有显著心脏毒性的强效化疗剂.
线粒体-溶解体相互作用对于细胞的健康和功能至关重要.
了解DOX诱导心脏毒性 (DIC) 的机制对于制定保护策略至关重要.

研究的目的:

为了研究胺三核酸结合蛋白2 (HINT2) 在缓解DIC.中所扮演的角色.
阐明HINT2在DOX治疗期间影响心脏功能的分子机制.

主要方法:

使用心脏特异性 提示2 淘汰赛小鼠和野生型小鼠接受DOX.治疗.
评估心脏功能,自流和溶酶体功能.
分析了氧化酸化,NAD+/NADH比,以及固醇调节元素结合蛋白2 (SREBP2) 的活性.
研究了尼古丁胺单核酸 (NMN) 补充和Hint2过度表达 (AAV9,腺病毒) 在体外和体内的影响.

主要成果:

在DOX治疗心脏中,HINT2表达的调高.
提示2:淘汰赛恶化了DOX诱导的心脏功能障碍,溶酶体损伤和自缺陷.
HINT2缺乏减少了复合I活性,并改变了NAD+/NADH比率,损害了 lysosomal 功能.
HINT2缺乏抑制了SREBP2的活性,影响了线粒体转录因子A (TFAM) 和复合物I.
补充NMN和提示2过度表达改善了DIC.

结论:

HINT2作为一个关键的心脏保护因子,防止DOX诱导的心脏毒性.
HINT2通过恢复NAD+/NADH平衡,溶酶体完整性和自性来保持心脏功能.
针对HINT2或NMN补充的治疗策略显示,它有望预防与DOX相关的心力衰竭.

关键词:

暗示2 暗示2 暗示2 这是NAD+/NADH.自自是自的过程.德克索鲁比辛 (doxorubicin) 是一种药物.lysosome 溶解酶体是如何形成的

更多相关视频

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo

Published on: May 16, 2020

Hybrid Cell Analysis System to Assess Structural and Contractile Changes of Human iPSC-Derived Cardiomyocytes for Preclinical Cardiac Risk Evaluation

Hybrid Cell Analysis System to Assess Structural and Contractile Changes of Human iPSC-Derived Cardiomyocytes for Preclinical Cardiac Risk Evaluation

Published on: October 20, 2022

相关概念视频

Electron Transport Chain: Complex I and II

Electron Transport Chain: Complex I and II

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...

Heart Failure Drugs: Inotropic Agents

Heart Failure Drugs: Inotropic Agents

Positive inotropic agents are commonly used as the first line of treatment for heart failure. One such agent is digoxin, derived from the genus Digitalis, which has been known for centuries but effectively utilized since 1785. However, these cardiac glycosides can have potentially toxic effects due to their mechanism of action, which involves inhibiting Na+/K+-ATPase and increasing contractility. Digoxin is absorbed orally and distributed in various tissues, including the CNS. It has a long...

Transducer Mechanism: Enzyme-Linked Receptors

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

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...