Ohta H, Yatomi Y, Sweeney E A, Hakomori S, Igarashi Y
Biomembrane Institute, Seattle, WA 98119.
FEBS Lett. 1994 Dec 5;355(3):267-70. doi: 10.1016/0014-5793(94)01218-0.
Treatment of human neutrophils with tumor necrosis factor-alpha (TNF-alpha) resulted in an increase in concentration of ceramide and its catabolite, sphingosine. Sphingosine, a potent endogenous protein kinase C (PKC) inhibitor, as well as TNF-alpha, induced internucleosomal DNA fragmentation and morphological changes characteristic of apoptotic cells. Ceramide and sphingosine-1-phosphate, the initial product of sphingosine catabolism, did not cause apoptosis under our experimental conditions. In addition, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) and N,N-dimethylsphingosine (DMS), known as PKC inhibitors, also induced apoptosis, suggesting that induction of apoptosis by sphingosine may be related to inhibition of PKC activity. These results indicate that sphingosine deacylated from ceramide may be an endogenous modulator mediating apoptotic signals by TNF-alpha in neutrophils.
用肿瘤坏死因子-α（TNF-α）处理人中性粒细胞会导致神经酰胺及其分解代谢产物鞘氨醇的浓度增加。鞘氨醇是一种有效的内源性蛋白激酶C（PKC）抑制剂，与TNF-α一样，可诱导核小体间DNA片段化以及凋亡细胞特有的形态变化。在我们的实验条件下，神经酰胺和鞘氨醇分解代谢的初始产物鞘氨醇-1-磷酸不会导致细胞凋亡。此外，已知的PKC抑制剂1-（5-异喹啉磺酰基）-2-甲基哌嗪（H7）和N，N-二甲基鞘氨醇（DMS）也可诱导细胞凋亡，这表明鞘氨醇诱导的细胞凋亡可能与PKC活性的抑制有关。这些结果表明，从神经酰胺去酰基化而来的鞘氨醇可能是一种内源性调节剂，在中性粒细胞中介导TNF-α的凋亡信号。
