Friday, June 18, 2010

ROS Revisited

Reactive oxygen species have become an important topic in regards to normal cellular function and their potential for carcinogenesis. Originally ROS were only thought to be released by phagocytic cells as a part of the host defense response, now it is clear that they have a role in a number of normal cellular processes. Recent work has demonstrated that ROS have a role in cell signaling, including; apoptosis; gene expression; and the activation of cell signaling cascades [1]. It should be noted that ROS can serve as both intra- and inter-cellular messengers. The short half life of most reactive oxygen species makes them an idea intracellular messenger.

As cells proliferate, they move through a coordinated process of cell growth, DNA duplication and mitosis referred to as the cell cycle. The cell cycle is a tightly regulated process with several checkpoints. Each one of these checkpoints is regulated by proteins and protein complexes that are influenced by the oxidative state of the cell. The relationship between the Redox state and cell cycle control is described in great detail in a review by Burhans and Heintz [2].

High levels of ROS, which can lead to cellular damage, oxidative stress and DNA damage, can elicit either cell survival or apoptosis mechanisms depending on severity and duration of exposure. Intra-cellularly, ROS species, in conjunction with antioxidant enzymes, are believed to play a role in turning enzymes on and off by redox signaling in a manner akin to that of the cAMP second messenger system [3]. Stimulated cells exhibit pronounced increases in ROS activity.

Figure 1. DCF Fluorescence in Stimulated Cells Measured over Time.



The integral role that ROS compounds have been shown to play in cellular growth and multiplication has makes them and/or the enzymes that produce and regulate their production potential chemotherapeutic drug targets. In addition the general redox status of the cell has been suggested to act as a cellular growth control mechanism. As cancer cells seem more susceptible to perturbations in the cellular redox-state, therapeutic agents that alter it have the potential to be effective antitumor agents.

Several different fluorescent and luminescent markers have been developed to assess ROS, particularly H2O2 in cells and tissues. The multimode readers from BioTek, such as the Synergy H4, Synergy 2, and Synergy Mx are ideal reader platforms for quantitation of these compounds and many others associated reactive oxygen species.

References

1.Hancock, J.T., R. Desikan, S.J. Neill, (2001) Role of Reactive Oxygen Species in Cell Signaling Pathways. Biochemical and Biomedical Aspects of Oxidative Modification, 29(2):345-350.

2.Burhans, W. and N. Heintz (2009) The Cell Cycle is a Redox Cycle: Linking phase-specific targets to cell fate. Free Radical Biology and Medicine. 47:1282-1294.\

3.Hou Y.C., Janczuk A. and Wang P.G. (1999) Current trends in the development of nitric oxide donors. Curr. Pharm. Des. June, 5 (6): 417–471.

No comments:

Post a Comment