HO-1-SIRT1轴的失调与AngII诱导的脂肪细胞功能障碍有关
Hari Vishal Lakhani1, Mishghan Zehra1, Sneha Pillai1
1Department of Surgery, Internal Medicine, and Biomedical Sciences, Joan C Edwards School of Medicine, Marshall University, Huntington, United States of America.
概括
血红素氧化酶-1 (HO-1) 诱导通过恢复氧化还原平衡和拯救Sirtuin-1 (SIRT1) 来减轻 ангиотензин II (AngII) 对脂肪细胞的有害影响. 这突出了HO-1作为代谢功能障碍的治疗点.
科学领域:
- 代谢研究研究 代谢研究
- 脂肪组织生物学 脂肪组织生物学
- 氧化应激和还氧化生物学
背景情况:
- 氨酸-阿尔多素系统 (RAAS) 的组成部分氨酸II (AngII) 与脂肪组织功能障碍有关.
- 由AngII诱导的氧化应激可以抑制细胞代谢的关键调节者Sirtuin-1 (SIRT1).
- 血红蛋白氧化酶-1 (HO-1) 是一种抗氧化酶,已知可以抵消氧化应激并改善脂肪细胞表型.
研究的目的:
- 研究AngII诱导的氧化应激通过HO-1下调抑制脂肪细胞SIRT1的机制.
- 为了确定HO-1诱导是否可以拯救SIRT1,改善氧化应激,并改善脂肪细胞功能障碍.
- 探索矿物质皮质类受体 (MR) 在AngII介导对脂肪细胞的影响中的作用.
主要方法:
- 实验中使用了与AngII治疗的小鼠前脂肪细胞,HO-1诱导剂原 (CoPP) 和HO-1抑制剂锡 mesoporphyrin (SnMP).
- 评估了脂质积累,超氧化物水平,炎症性细胞因子 (IL-6,TNF-alpha),腺素,MR和SIRT1的表达.
- 使用siRNA与CoPP治疗结合,研究了SIRT1的作用.
主要成果:
- AngII治疗增加了脂质积累,超氧化物和炎症性细胞因子,同时降低了前脂质细胞中的皮菌素.
- HO-1诱导 (CoPP) 减弱了AngII诱导的有害影响,而HO-1抑制 (SnMP) 则可以逆转这些有害影响.
- AngII上调了MR和抑制了SIRT1,由HO-1诱导挽救的效果;HO-1的好处是通过SIRT1.1进行的.
结论:
- HO-1诱导有效地恢复了细胞的氧化还原平衡,并在AngII压力下拯救了脂肪细胞中的SIRT1表达.
- HO-1激活减弱了AngII对脂肪细胞功能和全身代谢概况的不良影响.
- 向HO-1为管理与RAAS失调相关的代谢障碍提供了一个有希望的治疗策略.
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