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Inhibition of receptor internalization attenuates the TNFalpha-induced ROS generation in non-phagocytic cells

Chang-Hoon Woo1, Tae-Hee Kim, Jung-A Choi

  • 1School of Life Sciences and Biotechnology, Korea University, 5-1 Anam-dong, Seoul 136-701, Republic of Korea.

Biochemical and Biophysical Research Communications
|November 14, 2006
PubMed

Insights

Tumor necrosis factor-alpha (TNFα) triggers reactive oxygen species (ROS) production, essential for downstream signaling. Our study reveals that TNFα receptor internalization is crucial for this ROS generation in non-phagocytes.

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Immunology

Background:

  • Reactive oxygen species (ROS) act as key signaling molecules in cellular processes.
  • Tumor necrosis factor-alpha (TNFα) signaling involves ROS, but the induction mechanism remains unclear.

Purpose of the Study:

  • To investigate the role of TNFα receptor internalization in ROS generation.
  • To elucidate the mechanism linking TNFα to ROS production and downstream signaling.

Main Methods:

  • Inhibition of receptor internalization using monodansyl cadaverine (MDC).
  • Expression of a dominant-negative dynamin mutant (dynamin K44A) to block internalization.
  • Measurement of intracellular ROS production.
  • Analysis of mitogen-activated protein kinase (MAPK) signaling.

Main Results:

  • TNFα-induced ROS production was significantly inhibited by blocking receptor internalization.
  • The dynamin K44A mutant attenuated TNFα-induced ROS.
  • Inhibition of receptor internalization suppressed TNFα-induced MAPK stimulation.

Conclusions:

  • Receptor internalization is a necessary step for TNFα-induced ROS generation.
  • This internalization process is critical for subsequent downstream signaling, including MAPK activation, in non-phagocytic cells.

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