Abstract
Reactive oxygen species (ROS) are important regulatory molecules implicated in the signaling cascade triggered by tumor necrosis factor (TNF)α, although the events through which TNFα induces ROS generation are not well characterized. Here, we report that TNFα-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 (dynaminK44A) that had been shown to be defective in internalization significantly attenuated the TNFα-induced intracellular ROS production. Importantly, the inhibition of receptor internalization suppressed TNFα signaling to mitogen-activated protein kinases (MAPKs) stimulation. Together, our results suggest that receptor internalization is somehow necessary for the TNFα-induced ROS generation and subsequent intracellular downstream signaling in non-phagocytes.
Original language | English |
---|---|
Pages (from-to) | 972-978 |
Number of pages | 7 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 351 |
Issue number | 4 |
DOIs | |
State | Published - 29 Dec 2006 |
Bibliographical note
Funding Information:This work was supported by the Frontier 21 Programs (Proteomics), the BioDiscovery Research Program of the Korea Ministry of Science and Technology, and the SRC program (Aging and Apoptosis Research Center) (2002) of the Korea Science and Engineering Foundation (KOSEF).
Keywords
- Non-phagocytes
- Nox
- ROS
- Receptor internalization
- Signal transduction
- TNFα