Cycloserine and threo-dihydrosphingosine inhibit TNF-alpha-induced cytotoxicity: evidence for the importance of de novo ceramide synthesis in TNF-alpha signaling.
Cycloserine and threo-dihydrosphingosine inhibit TNF-alpha-induced cytotoxicity: evidence for the importance of de novo ceramide synthesis in TNF-alpha signaling.
复制标题
环丝氨酸和苏式二氢鞘氨醇抑制 TNF-α 诱导的细胞毒性：神经酰胺从头合成在 TNF-α 信号转导中重要性的证据。
DOI：
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
H. de Groot
中科院分区：
文献类型：
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作者：
Sybille G. E. Meyer;H. de Groot
Measuring the cell death induced by tumor necrosis factor (TNF-alpha) in L929 cells, we discovered for the first time that L-cycloserine, an established inhibitor of serine palmitoyltransferase, as well as DL-threo-dihydrosphingosine (threo-DHS, threo-sphinganine) significantly protected against TNF-alpha-induced cytotoxicity. Under the same conditions sphingosine and DL-erythro-dihydrosphingosine (erythro-DHS) did not change TNF-alpha-induced cytotoxicity, thus underlining the specificity of threo-DHS. In serine-labeled cells, newly (de novo) synthetized labeled ceramide was significantly diminished by threo-DHS alone or together with TNF-alpha, which makes the (dihydro) ceramide synthase the likely target of threo-DHS. These results suggest the decisive role of ceramide de novo synthesis in TNF signaling.
