Reactive Oxygen Species

Reduced by Contact

Science's STKE  12 Dec 2000:
Vol. 2000, Issue 62, pp. tw2
DOI: 10.1126/stke.2000.62.tw2

Reactive oxygen species (ROS) and the redox state of a cell have been implicated in several signal transduction cascades including those that regulate cell proliferation. Specifically, signaling by several growth factors, including epidermal growth factor (EGF), produces a transient increase in ROS. One effect of increases in ROS is the inactivation of tyrosine phosphatases. Pani et al. found that the redox status of cells in culture was different in sparse and dense cultures (sparse cultures have more ROS than dense cultures) and that this difference correlated with whether the cells exhibited contact inhibition. Dense cultures had lower levels of the active [guanosine triphosphate (GTP)-bound] form of the small GTPase Rac-1. Treatment of sparse cultures with drugs to inhibit leukotriene biosynthesis decreased the levels of ROS to those measured in dense cultures, suggesting that Rac-1 may stimulate leukotriene biosynthesis as a mechanism to increase ROS in sparsely cultured cells. The authors also used several other drugs to regulate tyrosine phosphatase activity (sodium orthovanadate) and redox status (dithiothreitol) of the cells; however, none of the agents used were very specific. With that caveat, the results were consistent with the hypothesis that dense cells have lower levels of ROS, which allow increased activity of tyrosine phosphatases, thereby attenuating the ability of growth factors to stimulate proliferation. Thus, the regulation of the levels of ROS through regulation of the activity of proteins such as Rac-1 may be one mechanism by which the inhibition of cell proliferation in response to cell-cell contact occurs.

Pani, G., Colavitti, R., Bedogni, B., Anzevino, R., Borrello, S., and Galeotti, T. (2000) A redox signaling mechanism for density-dependent inhibition of cell growth. J. Biol. Chem. 275: 38891-38899. [Abstract] [Full Text]