慢性阿里碳化合物受体活性损害肌肉线粒体功能与烟草吸烟
Liam F Fitzgerald1, Jacob Lackey2, Ahmad Moussa2
1Department of Physical Therapy, University of Florida, Gainesville, FL, USA.
Journal of cachexia, sarcopenia and muscle
|February 9, 2024
概括
慢性吸烟会通过激活基碳水化合物受体 (AHR) 来损害骨肌肉,导致线粒体功能障碍,特别是在男性中. 准AHR可能会改善吸烟者和COPD患者的肌肉健康.
科学领域:
- 肌肉生理学和毒理学
- 吸烟引起的损伤的分子机制
- 亚利碳化合物受体 (AHR) 信号传递
背景情况:
- 慢性吸烟会导致骨肌肉功能障碍,独立于心肺呼吸系统的影响.
- 烟草烟雾对肌肉有毒性的确切机制尚未完全理解.
- 酸受体 (AHR) 被烟草烟雾激活,研究了它在肌肉中的作用.
研究的目的:
- 研究基碳化合物受体 (AHR) 在通过长期暴露于香烟烟雾引起的骨肌功能障碍中扮演的角色.
- 为了确定AHR激活对肌肉能量和功能的影响.
- 探索骨肌中AHR激活的潜在的性别依赖性影响.
主要方法:
- 量化COPD患者和对照者的骨肌肉中的AHR相关基因表达,以及暴露在香烟烟雾中的或不暴露在香烟烟雾中的小鼠.
- 使用骨肌特异性AHR淘汰赛小鼠和具有AHR突变表达的小鼠.
- 评估肌肉大小,收缩功能,线粒体能量,并进行RNA测序.
主要成果:
- 慢性肺炎患者和暴露于烟雾的小鼠在骨肌肉中显示出较高水平的AHR和相关基因 (CYP1B1,CYP1A1).
- 在对照小鼠中,暴露于香烟烟雾会使线粒体的氧化酸化减少约50%.
- 雄性小鼠的AHR删除减轻了烟雾引起的线粒体功能障碍,而雌性小鼠没有显著差异,表明性别依赖的影响.
结论:
- 由于暴露于香烟烟雾的慢性AHR激活与骨肌肉的生物能量缺陷有关,主要是男性.
- 吸烟者的AHR激活有助于减少肌肉氧化能力.
- 在慢性阻塞性肺病 (COPD) 中,AHR对抗是一种改善肌肉功能的潜在治疗策略.
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