氧化应激会诱导NF-kappaB的核转位,而不会降解IkappaBalphapha
1Department of Surgery, University of Washington, Seattle 98104-2924, USA.
Circulation
|November 24, 1999
概括
氧化应激通过一种新的途径激活心脏细胞中的核因子-kappaB (NF-kappaB). 这种机制绕过了通常的IkappaBalpha降解,这表明氨酸酸化在缺血-再输液损伤期间的NF-kappaB信号传递中起着独特的作用.
科学领域:
- 心血管生物学 心血管生物学
- 分子生物学分子生物学
- 细胞信号传输 细胞信号传输
背景情况:
- 核因子-kappaB (NF-kappaB) 是一种氧化应激反应的转录因子,参与基因表达.
- 在缺血和再输血期间NF-kappaB激活的精确机制在很大程度上是未知的.
研究的目的:
- 研究由氧化应激诱导的人类心脏组织和内皮细胞中NF-kappaB激活的细胞机制.
- 阐明在缺血-再输液过程中参与NF-kappaB激活的信号通路.
主要方法:
- 从心肺旁路手术中分析人类心脏组织.
- 在体外研究中,使用人静脉内皮细胞 (HUVEC) 接受过氧缺氧,再氧化和过氧化 (H2O2) 暴露.
- 电泳运动转移测试 (EMSA) 和西部涂抹测试,以评估NF-kappaB激活和IkappaBalpha降解.
主要成果:
- 观察到NF-kappaB激活在心脏组织缺血后和再输血.
- 低氧/低氧化和H2O2治疗诱导了HUVEC中的NF-kappaB激活.
- H2O2诱导的NF-kappaB激活因氨酸酸酶抑制而增强.
- 氧化应激诱导的NF-kappaB激活独立于IkappaBalpha降解发生,与瘤缩因子-α诱导的激活不同.
结论:
- 在氧化应激过程中,内皮细胞中存在NF-kappaB激活的刺激特异性机制.
- 这一途径独立于IkappaBalpha降解而运作.
- 铁酸酸化可能在氧化应激中介的NF-kappaB激活中发挥关键作用.
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