Differential activation of heat shock and nuclear factor κB transcription factors in postischemic reperfused rat liver
Differential activation of heat shock and nuclear factor κB transcription factors in postischemic reperfused rat liver
复制标题
缺血再灌注大鼠肝脏热休克和核因子κB转录因子的差异激活
作者：
L. Tacchini;L. Radice;G. Pogliaghi;A. Bernelli‐Zazzera
本研究的目的是研究转录因子热休克因子（HSF）和核因子κB（NF-κB）在缺血后再灌注肝脏中的行为，特别注意激活的时程和机制的可能差异，这可能有助于确定它们在肝脏对再灌注的反应中的作用。通过夹闭左外侧和中间肝叶的肝门蒂诱导缺血; 1小时后移除夹。部分大鼠在缺血前30分钟和再灌注时腹腔注射IL-1受体拮抗剂（IL-1 RA）。NF-κB与相应共有序列的结合在再灌注30分钟后被激活，并且在再灌注1小时后仍然增加。在IL-1 RA处理的大鼠中，活化受到抑制; NF-κB持续存在于与抑制剂IκB相关的胞质溶胶中，并且可以在体外人为活化。超凝胶位移实验表明，p50和p65这两个亚基参与了结合的激活。相比之下，HSF与相应的共有序列热休克元件（HSE）的结合在缺血结束时就已被激活，再灌注30分钟后进一步增加，但再灌注1小时后下降;更重要的是，用IL-1 RA预处理大鼠不会抑制它。总之，尽管HSF和NF-κB都被缺血再灌注激活，但这两种转录因子激活的时间过程和机制存在明显差异。HSF的激活直接依赖于缺血期间发生的一些事件; NF-κB仅在再灌注和同时发生的氧化应激后通过可被IL-1 RA抑制的间接机制被激活。分离这两种转录因子在缺血后再灌注中的激活的可能性具有前瞻性的临床意义。
The aim of this study was to investigate the behavior of the transcription factors, heat‐shock factor (HSF) and nuclear factor κB (NF‐κB), in postischemic reperfused liver, with particular attention paid to possible differences in the time‐course and mechanism of activation, which may help in defining their role in the response of the liver to reperfusion. Ischemia was induced by clamping the hilar pedicle of the left lateral and median liver lobes; the clamp was removed after 1 hour. Some rats were treated intraperitoneally with IL‐1 receptor antagonist (IL‐1RA) 30 minutes before ischemia and at the time of reperfusion. Binding of NF‐κB to the corresponding consensus sequence is activated after 30 minutes of reperfusion, and is still increased 1 hour after reperfusion. Activation is suppressed in rats treated with IL‐1RA; NF‐κB persists in the cytosol associated with the inhibitor, IκB, and can be artifactually activated in vitro. Super‐gel shift experiments revealed that the two subunits, p50 and p65, are involved in the activation of binding. In contrast, binding of HSF to the corresponding consensus sequence, heat shock element (HSE), is already activated at the end of ischemia, shows a further increase after 30 minutes of reperfusion, but declines 1 hour after reperfusion; more importantly, it is not inhibited by pretreatment of the rat with IL‐1RA. In conclusion, although both HSF and NF‐κB are activated by ischemia‐reperfusion, there are clear differences in time‐course and mechanism of activation of the two transcription factors. Activation of HSF depends directly on some events occurring during ischemia; NF‐κB is activated only after reperfusion and the concurrent oxidative stress, by an indirect mechanism that can be suppressed by IL‐1RA. The possibility of dissociating the activation of these two transcription factors in postischemic reperfusion can have a prospective clinical relevance.
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DOI：
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发表时间：
1995-04
期刊：
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
影响因子：
--
作者：
M. Fitzgerald;E. Webber;Justine R. Donovan;N. Fausto
通讯作者：
M. Fitzgerald;E. Webber;Justine R. Donovan;N. Fausto
DOI：
10.1152/ajpgi.1996.271.3.g494
发表时间：
1996-09-01
影响因子：
4.5
作者：
Arteel, GE;Raleigh, JA;Thurman, RG
通讯作者：
Thurman, RG
DOI：
10.1152/ajpgi.1996.270.6.g909
发表时间：
1996-06-01
影响因子：
4.5
作者：
Rai, RM;Yang, SQ;Diehl, AM
通讯作者：
Diehl, AM
由抗原受体特异性单克隆抗体诱导的克隆辅助 T 细胞系的生长：白细胞介素 1 受体的表达需要白细胞介素 2 受体。
DOI：
--
发表时间：
1984
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kaye,J;Gillis,S;Mizel,SB;Shevach,EM;Malek,TR;Dinarello,CA;Lachman,LB;JanewayJr,CA
通讯作者：
JanewayJr,CA