肌肉衍生的IL-1β通过NBR1-p62-Nrf2途径调节肌肉中的ECSOD表达,在癌症缓解症期间
Mami Yamada1, Eiji Warabi2, Hisashi Oishi3
1Graduate School of Science, Nagoya City University, Nagoya, Japan.
The Journal of physiology
|August 21, 2024
概括
癌症缓解症增加了骨肌肉中的抗氧化酶细胞外超氧化脱酶 (EcSOD). 这通过介质素-1β (IL-1β) 信号发生,激活p62-Nrf2通路,为肌肉消耗提供潜在的治疗点.
科学领域:
- 肌肉生理学和氧化应激研究.
- 癌症生物学和缓解症机制.
- 细胞适应中的分子信号通路.
背景情况:
- 氧化应激是癌症缓解症期间肌肉质量和功能丧失的关键因素.
- 内生抗氧化剂系统可以抵消这些有害影响.
- 细胞外超氧化脱酶 (EcSOD) 是一种重要的抗氧化酶.
研究的目的:
- 为了研究 EcSOD 在癌症缓解症期间肌肉适应中的作用.
- 阐明癌症引起的肌肉缩中ECSOD调节的基础分子机制.
- 确定潜在的治疗点,以减轻癌症缓解症中的肌肉损失.
主要方法:
- 使用了易斯肺癌 (LLC) 癌症缓冲症的小鼠模型.
- 分析了LCL携带小鼠的延伸指纹长肌.
- 在试验室研究中使用C2C12神经管,涉及IL-1β治疗.
- 使用肌肉特定的淘汰赛小鼠模型 (p62 skmKO,Nrf2 skmKO) 调查了p62和Nrf2的作用.
主要成果:
- 在卡塞克斯小鼠的延伸指纹长肌 (extensor digitorum longus muscle) 中,ECSOD水平增加.
- 移植LLC增加了IL-1β的表达和从肌肉纤维释放.
- 在试验室内IL-1β治疗增加了NBR1,p62酸化,Nrf2核转位和EcSOD蛋白.
- 肌肉内IL-1β注射刺激了体内ECSOD表达,这种效应被p62和Nrf2肌肉特异性淘汰赛所阻断.
- 针对p62有效地以Nrf2-依赖的方式驱动肌肉ECSOD表达.
结论:
- 癌症缓解症通过IL-1β介导NBR1-p62-Nrf2通路的激活诱导骨肌肉中的ECSOD表达.
- 这种机制突出显示了ECSOD在抗癌缓解症诱导的肌肉缩方面的保护作用.
- 针对IL-1β下游的p62-Nrf2通路,是对抗癌症肌肉消耗的有希望的治疗策略.
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