Selective inhibition of STAT3 phosphorylation by sodium salicylate in cardiac fibroblasts.

Selective inhibition of STAT3 phosphorylation by sodium salicylate in cardiac fibroblasts.
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水杨酸钠选择性抑制心脏成纤维细胞中 STAT3 磷酸化。

DOI:
10.1016/s0006-2952(02)00853-5
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发表时间:
2002
影响因子:
5.8
通讯作者:
Brecher,Peter
Brecher,Peter
中科院分区:
医学2区
文献类型:
--
作者:
Wang,Zhongyan;Jiang,Bingbing;Brecher,Peter

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以大鼠心肌成纤维细胞为模型,研究水杨酸对γ-干扰素(IFN-γ)诱导的信号转导子和转录激活子(STAT)磷酸化和核转位的影响,为水杨酸抗炎作用的研究提供可能的模型。水杨酸盐抑制STAT 1和STAT 3的酪氨酸磷酸化,但对STAT 3的活化有更明显的影响。水杨酸预处理防止核转位和DNA结合活性的STAT 1和STAT 3,分别通过免疫印迹和凝胶迁移试验进行评估。除了引起酪氨酸残基的磷酸化之外,IFN-γ还使STAT 3和STAT 1在丝氨酸727处磷酸化。水杨酸减弱了STAT 3的酪氨酸和丝氨酸磷酸化,也抑制了细胞外信号调节激酶(ERK)的激活,暗示水杨酸对ERK的作用可能是减弱STAT 3激活的机制。水杨酸可能会影响信号级联通过改变细胞的氧化还原状态的可能性进行了检查,其效果不同于其他还原剂。水杨酸盐确实减弱了过氧化氢对STAT磷酸化的影响,这与水杨酸盐和细胞内活性氧之间相互作用的机制一致。
The effects of salicylate on the phosphorylation and nuclear translocation of signal transducers and activators of transcription (STATs) induced by interferon-γ (IFN-γ) were studied in rat cardiac fibroblasts as a possible model for the anti-inflammatory effects of salicylate on this signaling pathway. Salicylate inhibited the tyrosine phosphorylation of both STAT1 and STAT3, but had a more pronounced effect on STAT3 activation. Salicylate pretreatment prevented both the nuclear translocation and the DNA-binding activity of STAT1 and STAT3, assessed by immunoblotting and gel shift assays, respectively. In addition to causing phosphorylation at tyrosine residues, IFN-γ also phosphorylated STAT3 and STAT1 at serine 727. Salicylate attenuated both tyrosine and serine phosphorylations of STAT3, and also suppressed extracellular signal-regulated kinase (ERK) activation, implicating the effect of salicylate on ERK as a possible mechanism for attenuating STAT3 activation. The possibility that salicylate might affect signaling cascades by altering the redox state of the cells was examined, and its effects differed from those of other reducing agents. Salicylate did attenuate the effects of hydrogen peroxide on STAT phosphorylation, consistent with a mechanism involving an interaction between salicylate and reactive oxygen species within the cell.
受刺激的粒细胞氧化水杨酸盐:这些药物在生物系统中充当自由基清除剂的证据。
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