Acetaldehyde Inhibits NF-κB Activation through IκBα Preservation in Rat Kupffer Cells

Acetaldehyde Inhibits NF-κB Activation through IκBα Preservation in Rat Kupffer Cells
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乙醛通过保存大鼠 Kupffer 细胞中的 IκBα 抑制 NF-κB 激活

DOI:
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发表时间:
1998
期刊:
影响因子:
--
通讯作者:
A. Nanji
A. Nanji
中科院分区:
--
文献类型:
--
作者:
K. Jokelainen;P. Thomas;K. Lindros;A. Nanji

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背景和目的:乙醛脱氢酶抑制剂治疗可导致乙醇喂养大鼠肝脏乙醛水平升高,并可预防肝脏炎症和坏死。这伴随着IκBα的保存和核因子(NF)-κB活化的降低。本研究旨在阐明乙醛对LPS刺激的大鼠Kupffer细胞IκBα降解和NF-κB活化的影响。方法:从雄性Sprague-Dawley大鼠分离Kupffer细胞,用不同浓度的乙醛(25-100 μM)预孵育。此后,用LPS刺激细胞,并制备胞质和核级分。IκBα和p65蛋白以及NF-κB的活化进行了评估。结果。在LPS刺激的大鼠Kupffer细胞中,乙醛减少了IκBα的蛋白水解降解,抑制了胞浆p65蛋白的核转位,因此显著降低了NF-κB的活化。结论。乙醛明显参与了大鼠Kupffer细胞中IκBα蛋白的稳定和NF-κB活化的抑制。乙醛可与IκBα形成加合物,从而使蛋白质不易降解。
Abstract Background and aims.Treatment with acetaldehyde dehydrogenase inhibitors leads to increased liver acetaldehyde levels and prevents hepatic inflammation and necrosis in ethanol-fed rats. This is accompanied by IκBα preservation and decreased activation of nuclear factor (NF)-κB. The presentin vitrostudy was aimed to clarify whether acetaldehyde has an effect on degradation of IκBα and activation of NF-κB in LPS-stimulated rat Kupffer cells.Methods.Kupffer cells were isolated from male Sprague–Dawley rats and preincubated with various concentrations of acetaldehyde (25–100 μM). Thereafter the cells were stimulated with LPS, and cytosolic and nuclear fractions were prepared. IκBα and p65 proteins and activation of NF-κB were evaluated.Results.In LPS-stimulated rat Kupffer cells, acetaldehyde diminished proteolytic degradation of IκBα, inhibited nuclear translocation of cytosolic p65 protein, and, accordingly, markedly decreased NF-κB activation.Conclusions.Acetaldehyde is clearly involved in the stabilization of IκBα protein and suppression of NF-κB activation in rat Kupffer cells. Acetaldehyde may form an adduct with IκBα, thus making the protein less susceptible to degradation.
DOI: 10.1016/0016-5085(95)90027-6
发表时间: 1995-01-01
期刊: GASTROENTEROLOGY
影响因子: 29.4
作者:
ADACHI, Y;MOORE, LE;THURMAN, RG
通讯作者: THURMAN, RG
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DOI: --
发表时间: 1985
期刊: Cancer research
影响因子: 11.2
作者:
Toth,CA;Thomas,P;Broitman,SA;Zamcheck,N
通讯作者: Zamcheck,N