Editors' ChoiceReactive Oxygen Species

Protective at Low Concentrations?

Science's STKE  28 Jun 2005:
Vol. 2005, Issue 290, pp. tw240
DOI: 10.1126/stke.2902005tw240

Reactive oxygen species (ROS), which are produced as normal by-products of aerobic metabolism, have been implicated in aging and in the pathogenesis of cancer, cardiovascular diseases, and neurodegenerative disorders. However, antioxidants have not shown consistent benefits against cardiovascular disease, and evidence that ROS may also play a protective role has begun to emerge. Tang et al. found that, in various cultured cells, low to moderate concentrations of H2O2 inhibited the enzymatic activity of Src family tyrosine kinases (SFKs) as well as their phosphorylation on a conserved tyrosine residue that is phosphorylated in the activated form. The in vitro catalytic activity of two recombinant SFKs, however, was not sensitive to H2O2. Although the tyrosine phosphorylation of all SFK-bound substrates immunoprecipitated from cell lysates was inhibited after brief exposure to H2O2 (10 minutes), the phosphorylation of a subset of proteins recovered after longer exposures (60 minutes). Immunofluorescence analysis of human umbilical vein endothelial cells (HUVECs) indicated that H2O2 inactivated SFKs at focal adhesions and the plasma membrane but that prolonged exposure led to the activation of cytoplasmic SFKs. Pretreatment of HUVECs with H2O2 inhibited the activation of extracellular signal-regulated kinase (ERK) by platelet-derived growth factor (PDGF) as well as thrombin- or tumor necrosis factor-α (TNF-α)-dependent expression of vascular cell adhesion molecule-1. Thus, the authors suggest that low concentrations of ROS may protect endothelial cells from inflammatory responses to cytokines and that this protective action is mediated through a rapid, but indirect, inactivation of SFKs.

H. Tang, Q. Hao, S. A. Rutherford, B. Low, Z. J. Zhao, Inactivation of Src family tyrosine kinases by reactive oxygen species in vivo. J. Biol. Chem. 280, 23918-23925 (2005). [Abstract] [Full Text]