N-n-butanyl haloperidol iodide通过调节AMPK/FoxO1信号传递来调节心脏保护作用
Binger Lu1, Zhuomin Wu1, Weiliang He2
1The First Affiliated Hospital, Shantou University Medical College, Shantou, China.
Journal of cellular and molecular medicine
|November 21, 2023
概括
N-n-butanyl haloperidol iodide (F2) 通过激活AMPK/FoxO1通路,减少氧化应激并增加抗氧化剂水平,保护心脏免受缺血/反损伤.
科学领域:
- 心血管研究研究心血管研究
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 心脏缺血/反 (I/R) 损伤受到显著的氧化还原失衡的影响.
- 叉头盒蛋白O1 (FoxO1) 是一种转录因子,可调节抗氧化剂以减轻I/R期间的氧化损伤.
- N-n-butanyl haloperidol iodide (F2) 是一种新型化合物,具有抑制氧化应激的能力.
研究的目的:
- 在体内小鼠I/R模型中研究F2的心脏保护作用.
- 确定F2的保护机制是否依赖于FoxO1转录因子.
- 阐明F2发挥其作用的分子途径.
主要方法:
- 使用心脏缺血/再输血 (I/R) 的体内小鼠模型.
- 进行F2预条件和评估I / R损伤,氧化应激标志物和抗氧化剂水平 (SOD2,催化酶).
- 使用特定抑制剂 (AS1842856,化合物C) 调查了FoxO1和AMP激活蛋白激酶 (AMPK) 的作用.
主要成果:
- F2预条件显著减少了I/R损伤,氧化应激和增加了抗氧化剂表达.
- 在F2处理后观察到FoxO1的核转位和AMPK的酸化.
- 抑制FoxO1或AMPK消除了F2的心脏保护作用,这表明途径依赖.
结论:
- F2预处理可显著保护心肌体I/R损伤.
- F2 的心脏保护作用通过AMPK/FoxO1 途径的激活来实现.
- 这项研究表明F2是缺血性心脏病的潜在治疗剂.
相关概念视频
01:26Heart 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
01:26Heart Failure Drugs: Inotropic Agents
596
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...
596
01:22PI3K/mTOR/AKT Signaling Pathway
3.6K
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...
3.6K
01:22Heart Failure Drugs: β-Blockers
344
β-adrenergic antagonists, commonly known as β-blockers, block the effects of sympathetic neurotransmitters such as noradrenaline (NA) and adrenaline (ADR). They have several beneficial effects in heart failure treatment. They reduce heart rate, the force of contraction, and cardiac muscle relaxation. They also slow the atrial-ventricular conduction rate and raise the threshold for arrhythmias. The concentration of β-blockers determines their effects on bronchodilation,...
344
01:27Adrenergic Antagonists: Pharmacological Actions of β-Receptor Blockers
853
β-receptor blockers significantly impact the cardiovascular system by counteracting catecholamine-induced sympathetic responses. These medications decrease heart rate, contractility, and cardiac output, potentially leading to cardiac depression, life-threatening bradycardia, and death. Therapeutically, β-blockers function as mild antihypertensives and are utilized in treating angina pectoris and cardiac arrhythmias. However, nonselective β-blockers inhibit β2-receptors in...
853
01:25cAMP-dependent Protein Kinase Pathways
6.4K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.4K