Inhibition of receptor internalization attenuates the TNFalpha-induced ROS generation in non-phagocytic cells.
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.
Woo
Chang-Hoon
CH
School of Life Sciences and Biotechnology, Korea University, 5-1 Anam-dong, Seoul 136-701, Republic of Korea.
Kim
Tae-Hee
TH
Choi
Jung-A
JA
Ryu
Ho-Cheol
HC
Lee
Jung Eun
JE
You
Hye-Jin
HJ
Bae
Yun-Soo
YS
Kim
Jae-Hong
JH
D002103:Cadaverine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009154:Mutation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D017382:Reactive Oxygen Species; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D020929:Mitogen-Activated Protein Kinase Kinases; D034281:Dynamins; C008542:monodansylcadaverine; D002103:Cadaverine