苏酸中介于炎症诱导的上腺皮质功能障碍
Ivona Mateska1, Anke Witt1, Eman Hagag1
1Institute of Clinical Chemistry and Laboratory Medicine, University Hospital, Technische Universität Dresden, Dresden, Germany.
eLife
|July 14, 2023
概括
严重的炎症会通过破坏细胞代谢,损害上腺功能. 这项研究揭示了炎症诱导的酸盐积累如何抑制类固醇激素的产生,提供了潜在的治疗点.
科学领域:
- 内分泌学 在内分泌学.
- 细胞的新陈代谢
- 炎症生物学 炎症生物学
背景情况:
- 脑下垂体-垂体-上腺 (HPA) 轴调节压力反应,炎症激活葡萄糖皮质激素的产生.
- 严重的炎症可能导致上腺功能障碍,降低其对上腺皮质激素 (ACTH) 的反应能力,但机制尚不清楚.
研究的目的:
- 阐明严重系统性炎症期间上腺功能障碍背后的分子和代谢机制.
- 为了识别在类固醇性上腺皮细胞中被破坏的关键通路.
主要方法:
- 在受到LPS诱导炎症的小鼠中进行的转录组,蛋白组和代谢组分析.
- 研究IL-1β-DNMT1-SDHB轴在调节细胞代谢和类固醇生成中的作用.
主要成果:
- 系统性炎症降低了上皮细胞中TCA循环和氧化酸化的调节.
- 炎症诱导的IL-1β上调DNMT1,导致SDHB促进体甲基化,酸盐积累和类固醇生成受损.
- 增加的酸盐会损害ATP合成,增强ROS的产生,减少类固醇的产生.
结论:
- IL-1β-DNMT1-SDHB-succinate轴是严重炎症中上腺功能障碍的关键调解器.
- 这一途径为降低类固醇生成提供了一种机械解释,并建议在危急疾病期间对上腺功能不充分的潜在治疗点.
相关概念视频
Skeletal Muscle Relaxants: Adverse Effects
401
Skeletal muscle relaxants are widely used for muscle paralysis and relieving pain following any muscle injury or stiffness. However, depending on the drug type, they can have adverse effects that range from mild to severe. Usually, nondepolarizing neuromuscular blockers have minimal side effects. For example, drugs like d-tubocurarine, cisatracurium, and rocuronium cause hypotension, whereas drugs like baclofen, when stopped abruptly, can lead to the recurrence of spastic conditions.
Unlike...
Unlike...
401
Antiasthma Drugs: Inhaled Corticosteroids and Glucocorticoids
308
Inhaled corticosteroids (ICS) are anti-inflammatory drugs used primarily in treating persistent asthma and providing long-term maintenance. They target the bronchial mucosa, the lining of the airways, to control inflammation, a critical factor in asthma progression and exacerbation.
ICS work through a multifaceted mechanism of action. They suppress the inflammatory response caused by the proliferation of TH cells. They also reduce the transcription of the IL-2 gene, which is involved in the...
ICS work through a multifaceted mechanism of action. They suppress the inflammatory response caused by the proliferation of TH cells. They also reduce the transcription of the IL-2 gene, which is involved in the...
308
Adrenal Gland Disorders
1.6K
Adrenal gland disorders manifest when the production of adrenal hormones deviates from the norm, resulting in either excessive or insufficient concentrations.
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
1.6K
Antiasthma Drugs: Leukotriene Modifiers
368
Leukotriene modifiers, or cysteinyl leukotriene receptor antagonists, are medications used to manage chronic asthma. These agents target specific inflammatory mediators produced during arachidonic acid metabolism, an essential process in generating inflammation in the body.
Leukotriene modifiers work through two distinct mechanisms:
Leukotriene modifiers work through two distinct mechanisms:
368
Adrenergic Agonists: Therapeutic Uses
858
Adrenergic agonists have diverse therapeutic uses across various medical conditions and emergencies.
Emergency and Intensive Care Unit (ICU) applications: Pressor agents increase blood pressure, heart rate, and contractility in shock and organ failure situations. Dopamine can induce vasodilation and stimulate adrenoceptors. Endogenous catecholamines are effective in treating cardiogenic shock. α2-agonists like clonidine can reverse anesthesia-induced hypertension.
Allergies and...
Emergency and Intensive Care Unit (ICU) applications: Pressor agents increase blood pressure, heart rate, and contractility in shock and organ failure situations. Dopamine can induce vasodilation and stimulate adrenoceptors. Endogenous catecholamines are effective in treating cardiogenic shock. α2-agonists like clonidine can reverse anesthesia-induced hypertension.
Allergies and...
858
Drugs Affecting Neurotransmitter Release or Uptake
1.1K
Certain drugs can affect how neurotransmitters called catecholamines, are released or taken back up in the adrenergic neuron. They can have different effects on the body's sympathetic transmission. Reserpine, a natural compound found in the Rauwolfia shrub, blocks a transporter called vesicular monoamine transporter (VMAT), which leads to a buildup of catecholamines in the cell and reduces sympathetic transmission. Another drug called guanethidine works in multiple ways, including blocking...
1.1K


