Zumbansen M, Stoffel W
Neuroscience Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Cologne, Joseph-Stelzmann-Strasse 52, D-50931 Cologne, Germany.
J Biol Chem. 1997 Apr 18;272(16):10904-9. doi: 10.1074/jbc.272.16.10904.
Tumor necrosis factor alpha (TNF-alpha) is one of the most potent inducer of the nuclear transcription factor kappaB (NF-kappaB). Activation of NF-kappaB is initiated by phosphorylation of the inhibitory subunit of the IkappaB-alpha-NF-kappaB complex. This leads to the dissociation of the complex and degradation of IkappaB-alpha. NF-kappaB is translocated into the nucleus. The sphingomyelin pathway is thought to mediate the TNF-alpha-induced activation of NF-kappaB by its second messenger ceramide. We have used the recently established acid sphingomyelinase-deficient mouse line (asmase-/- mice) to evaluate the role of acid sphingomyelinase in the TNF-alpha-induced signal transduction pathway. Here we present experimental evidence that acid sphingomyelinase is not involved in the TNF-alpha-induced activation of NF-kappaB. TNF-alpha treatment induced the dissociation and degradation of IkappaB-alpha and the nuclear translocation of NF-kappaB in embryonic fibroblasts derived from asmase-/- and wild type mice indiscriminately.
肿瘤坏死因子α（TNF-α）是核转录因子κB（NF-κB）最有效的诱导剂之一。NF-κB的激活是由IκB-α-NF-κB复合物抑制亚基的磷酸化引发的。这导致复合物解离以及IκB-α降解。NF-κB转位进入细胞核。鞘磷脂途径被认为通过其二信使神经酰胺介导TNF-α诱导的NF-κB激活。我们使用最近建立的酸性鞘磷脂酶缺陷小鼠品系（asmase-/-小鼠）来评估酸性鞘磷脂酶在TNF-α诱导的信号转导途径中的作用。在此我们提供实验证据表明酸性鞘磷脂酶不参与TNF-α诱导的NF-κB激活。TNF-α处理在源自asmase-/-和野生型小鼠的胚胎成纤维细胞中均无差别地诱导了IκB-α的解离和降解以及NF-κB的核转位。
