Ceramide generation by two distinct pathways in tumor necrosis factor α-induced cell death
Ceramide generation by two distinct pathways in tumor necrosis factor α-induced cell death
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DOI：
10.1016/s0014-5793(01)02625-4
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发表时间：
2001-08-10
期刊：
影响因子：
3.5
通讯作者：
Hannun, YA
中科院分区：
文献类型：
--
作者：
Dbaibo, GS;El-Assaad, W;Hannun, YA
神经酰胺在细胞中的积累可以通过鞘磷脂的水解或重新合成发生。在这项研究中，我们发现阻断新生神经酰胺合成可显著抑制神经酰胺的积累和随后的细胞死亡，以响应肿瘤坏死因子α。当细胞用谷胱甘肽（一种被认为是中性鞘磷脂酶的细胞调节剂）预处理时，神经酰胺积累在早期时间点的抑制作用随着细胞死亡的衰减而实现。这两种途径的抑制几乎完全抑制了神经酰胺的积累和细胞死亡，这表明神经酰胺产生的两种途径都受到了刺激。这说明了细胞因子作用中神经酰胺生成的复杂性。(C) 2001年由Elsevier Science B.V.代表欧洲生化学会联合会出版。
Ceramide accumulation in the cell can occur from either hydrolysis of sphingomyelin or by de novo synthesis. In this study, we found that blocking de novo ceramide synthesis significantly inhibits ceramide accumulation and subsequent cell death in response to tumor necrosis factor alpha. When cells were pre-treated with glutathione, a proposed cellular regulator of neutral sphingomyelinase, inhibition of ceramide accumulation at early time points was achieved with attenuation of cell death. Inhibition of both pathways achieved near-complete inhibition of ceramide accumulation and cell death indicating that both pathways of ceramide generation are stimulated. This illustrates the complexity of ceramide generation in cytokine action. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.