在ER压力下,通过依赖和不依赖阿迪波内克/T-cadherin的途径减少了外体细胞的产生
Keita Fukuoka1, Ryohei Mineo1, Shunbun Kita2
1Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
The Journal of biological chemistry
|July 31, 2023
概括
细胞内膜网膜 (ER) 的压力显著降低了外体细胞的产生,影响了依赖阿迪波涅克和独立的通路. 这一发现揭示了细胞压力如何影响细胞外囊泡的通信.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 外体 (细胞外囊泡) 对于废物处理和细胞间通信至关重要,在疾病中发挥作用.
- 虽然已知疾病中的外体载荷变化,但疾病过程 (如内质网膜 (ER) 应激) 对外体生产的影响还未得到充分研究.
- 作为一种有益的因素的阿迪波内克丁 (adiponectin) 之前已经被证明可以通过T-cadherin提升外体细胞水平.
研究的目的:
- 调查ER压力如何影响外体细胞的产生.
- 确定阿迪波内克丁/T-cadherin通路在ER压力中介作用对外体细胞生产中的作用.
- 阐明ER压力影响外体生物发生的分子机制.
主要方法:
- 在细胞培养模型中利用tunicamycin诱导ER压力.
- 评估了在存在或缺少皮菌素的情况下对外体细胞的产生.
- 从药理和遗传学上研究了激活需要内醇的酶1α (IRE1α) 的作用.
- 给小鼠服用尼卡米辛,以研究体内对循环中的EVs的影响.
- 分析了X盒结合蛋白1 (XBP1) 转录因子和干扰素通路的作用.
主要成果:
- 由尼卡米辛诱导的ER压力,减少了依赖于阿迪波内克丁/T-cadherin的外体细胞生成.
- IRE1α的激活降低了T-cadherin的调节,并降低了外体细胞的产生.
- 此外,ER压力也减弱了阿迪波内克丁/T-cadherin独立的外体细胞的产生.
- 在小鼠中,图尼卡米辛治疗减少了循环中的小EVs.
- 通过XBP1沉默激活IRE1α,上调了干扰素通路,导致外体细胞的产生减少.
结论:
- 细胞内膜网膜应激通过依赖和依赖阿迪波内克/T-cadherin的机制减少了外体细胞的产生.
- 涉及干扰素通路的IRE1α介导通路是ER压力减少外体生物发生的关键机制.
- 这些发现突出了细胞应激和细胞外囊泡生产调节之间的新联系.
相关概念视频
Psychoneuroimmunology: Diabetes and Cancer
47
Chronic stress has been linked to both the onset and progression of serious health conditions, including Type 2 diabetes and cancer. Type 2 diabetes, a widespread chronic illness, is closely associated with obesity and insulin resistance, both of which often worsen under stress. Studies indicate that men experiencing high levels of chronic stress face a 45% higher risk of developing diabetes compared to those with minimal stress. Stress triggers physiological responses that elevate blood...
47
Hypothalamic-Pituitary Axis
60.5K
The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.
60.5K
Role of ER in the Secretory Pathway
5.5K
Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
5.5K
Physiological Foundation of Stress
84
Stress triggers a coordinated physiological response involving the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. This dual activation ensures that the body is prepared for both immediate and prolonged stress management. The process begins with the perception of a stressor. This initial phase activates the SNS, leading to the rapid release of adrenaline (epinephrine) from the adrenal glands.
Role of the Sympathetic Nervous System
Adrenaline triggers the...
Role of the Sympathetic Nervous System
Adrenaline triggers the...
84
The Sympathetic Nervous System
95.7K
Overview
95.7K
Stress and Mental Health
182
Chronic stress profoundly affects mental health, significantly influencing mood, behavior, and overall quality of life. Research closely links chronic stress with mental health conditions such as depression, anxiety, and substance use disorders. Ongoing exposure to stress can lead to physiological and psychological changes, initiating a cycle of emotional distress and maladaptive coping mechanisms.
Individuals with depression often experience challenges in both their personal and professional...
Individuals with depression often experience challenges in both their personal and professional...
182


