Regulation of reactive-oxygen-species generation in fibroblasts by Rac1.


Journal Article

In a variety of non-phagocytic cell types, there is a marked increase in intracellular levels of reactive oxygen species (ROS), including superoxide and H2O2, after ligand stimulation. We demonstrate that in NIH 3T3 cells transient expression of constitutively activated forms of the small GTP-binding proteins Ras or Rac1 leads to a significant increase in intracellular ROS. An increase in intracellular ROS is also demonstrated after growth factor [platelet-derived growth factor (PDGF) or epidermal growth factor (EGF)] or cytokine [tumour necrosis factor-alpha (TNF-alpha) or interleukin (IL)-1 beta] stimulation of NIH 3T3 cells. Expression of a dominant negative allele of Rac1 inhibits the rise in ROS seen after Ras expression or after stimulation by either growth factors or cytokines. These results provide the first demonstration of the pathway by which ligand stimulation of ROS occurs in non-phagocytic cells and suggest that the family of Ras-related small GTP-binding proteins may function as regulators of the intracellular redox state.

Full Text

Cited Authors

  • Sundaresan, M; Yu, ZX; Ferrans, VJ; Sulciner, DJ; Gutkind, JS; Irani, K; Goldschmidt-Clermont, PJ; Finkel, T

Published Date

  • September 1996

Published In

Volume / Issue

  • 318 ( Pt 2) /

Start / End Page

  • 379 - 382

PubMed ID

  • 8809022

Pubmed Central ID

  • 8809022

Electronic International Standard Serial Number (EISSN)

  • 1470-8728

International Standard Serial Number (ISSN)

  • 0264-6021

Digital Object Identifier (DOI)

  • 10.1042/bj3180379


  • eng