Woo Chang-Hoon, Kim Tae-Hee, Choi Jung-A, Ryu Ho-Cheol, Lee Jung Eun, You Hye-Jin, Bae Yun-Soo, Kim Jae-Hong
School of Life Sciences and Biotechnology, Korea University, 5-1 Anam-dong, Seoul 136-701, Republic of Korea.
Biochem Biophys Res Commun. 2006 Dec 29;351(4):972-8. doi: 10.1016/j.bbrc.2006.10.154. Epub 2006 Nov 7.
Reactive oxygen species (ROS) are important regulatory molecules implicated in the signaling cascade triggered by tumor necrosis factor (TNF)alpha, although the events through which TNFalpha induces ROS generation are not well characterized. Here, we report that TNFalpha-induced ROS production was blocked by pretreatment with internalization inhibitor monodansyl cadaverine (MDC). Similarly, a transient expression of a GTP-binding and hydrolysis-defective dynamin mutant (dynamin(K44A)) that had been shown to be defective in internalization significantly attenuated the TNFalpha-induced intracellular ROS production. Importantly, the inhibition of receptor internalization suppressed TNFalpha signaling to mitogen-activated protein kinases (MAPKs) stimulation. Together, our results suggest that receptor internalization is somehow necessary for the TNFalpha-induced ROS generation and subsequent intracellular downstream signaling in non-phagocytes.
活性氧（ROS）是参与肿瘤坏死因子（TNF）α触发的信号级联反应的重要调节分子，尽管TNFα诱导ROS产生的具体机制尚未完全明确。在此，我们报道，内化抑制剂单丹磺酰尸胺（MDC）预处理可阻断TNFα诱导的ROS产生。同样，已证明在内化过程中存在缺陷的GTP结合和水解缺陷型发动蛋白突变体（发动蛋白（K44A））的瞬时表达，可显著减弱TNFα诱导的细胞内ROS产生。重要的是，受体内化的抑制抑制了TNFα向丝裂原活化蛋白激酶（MAPK）刺激的信号传导。总之，我们的结果表明，受体内化在某种程度上是TNFα诱导非吞噬细胞中ROS产生及随后细胞内下游信号传导所必需的。
