Reactive Oxygen Species (ROS), Antioxidants and Oxidative Stress, Lecture notes of Molecular biology

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Reactive Oxygen Species

(ROS), Antioxidants and

Oxidative Stress

Reactive oxygen species (ROS) are usually considered as molecules associated with oxidative stress, they are increasingly shown to take part in normal cellular signaling. This increases the possibilities of ROS to be toxicologically important. Even at concentrations that do not cause measurable structural alterations, cellular signaling may be disturbed. Antioxidants can be defined as any substance that significantly delays or prevents the oxidation of a substrate in an organism.

The antioxidant defenses thus include:

1. Enzymes that directly remove free radicals. 2. Molecules that decrease the formation of radicals (this includes proteins that minimize the availability of pro- oxidants, such as transferrin binding ferrous ions and metallothionein binding copper). 3. Molecules that prevent oxidative damage to biomolecules (e.g. histones protecting DNA and chaperones such as heat shock protein 90 (HSP90) protecting proteins). 4. Small molecules that either quench pro-oxidants or are preferentially oxidized by them to leave the more complex biomolecules intact (redox buffers).

There are two types of nonenzymatic redox-sensitive molecules:

1. Endogenous
2. Food-derived.

The most important of all the small molecules is glutathione.

It is present in most cells at millimolar concentrations.

Since glutathione is present in all organisms, it is often measured to indicate the redox state of organisms.

In this context, it is important to note that if glutathione is used to show the redox state of a cell, then the ratio between reduced and oxidized glutathione should be measured.

Thus, the ratio between oxidized and reduced glutathione can be used as a measure of the redox state of the cells. (6) Oxidized glutathione dimers can be exported from the cells. Oxidative conditions may affect glutathione synthesis, breakdown, and efflux. The effects observed may depend on the cell type. Consequently, the total glutathione concentration of cells cannot be used to indicate the redox status of the cells. An increase, no change, and a decrease in total cellular glutathione concentration have all been reported upon oxidative stress.