氧化会通过一种依赖于cGMP的途径,在成年猫类心肌中引起瘤缩因子-α的表达
D Kalra1, G Baumgarten, Z Dibbs
1Winters Center for Heart Failure Research, Cardiology Section, Department of Medicine, Veterans Administration Medical Center and Baylor College of Medicine, Houston, TX 77030, USA.
Circulation
|September 12, 2000
概括
氧化 (NO) 通过一种依赖cGMP的途径在心脏衰竭中触发瘤缩因子-α (TNF-alpha) 的产生. 这表明NO和TNF-alpha可能会在心力衰竭中产生自我维持的炎症反循环.
科学领域:
- 心血管研究研究心血管研究
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 瘤亡因子-α (TNF-α) 和氧化 (NO) 在失败的心脏中持续的同时表达尚未得到充分理解.
- 驱动这种同时表达的精确机制仍然难以捉摸.
研究的目的:
- 为了调查氧化 (NO) 是否足以诱导心脏中的瘤亡因子-α (TNF-alpha) 生物合成.
- 阐明涉及NO介导的TNF-α生成的信号通路.
主要方法:
- 使用缓冲器穿透的Langendorff心脏来自成年猫,接受了NO供体 (S-nitroso-N-acetylpenicillamine,SNAP) 的治疗.
- 使用NO灭剂 (C-PTIO),cGMP类似物 (8--cGMP) 和对抗剂 (ODQ,Rp-8-Br-cGMPS) 来剖析NO信号通路.
- 执行电泳运动转移测试 (EMSA) 来评估转录因子激活 (NF-kappaB,AP-1).
- 在孤立的心脏肌细胞中研究了IkappaBalpha的蛋白质修饰 (酸化,降解).
主要成果:
- 随着SNAP治疗剂量和时间的依赖,心肌TNF-alpha mRNA和蛋白质的增加.
- NO诱导的TNF-α生物合成是由cGMP途径调解的,涉及蛋白激酶G (PKG).
- 通过促进IkappaBalpha酸化和降解,SNAP和cGMP激活了NF-kappaB.
结论:
- 氧化 (NO) 通过一种依赖cGMP的途径引起TNF-α生物合成.
- 这种机制表明,NO和TNF-alpha可能会在失败的心脏中建立自我维持的炎症反回路.
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