Reactive oxygen species and superoxide dismutases: Role in joint diseases

This articles expressed the significance of SOD in neutralizing the superoxide anion from ROS that plays a vital role in inflammation, especially in inflammatory joint diseases. Proinflammatory factors (cytokines, prostaglandins) are released at sites of inflammation with ROS and NO. These are associated with decreased SOD concentrations in joint fluid, which are important in the protection against the harmful effects of the superoxide anion, which damages cells and the extracellular matrix. Other antioxidants that play a role in protective role are glutathione peroxidase, catalase, and liposoluble antioxidants(e.g.vitamin E). SOD catalyses the superoxide anion to dioxygen and peroxide. The peroxide is eliminated by glutathione peroxidase or catalase.

There are three SOD's studied: SOD1 found in the cytoplasm, SOD2 found in the mitochondria, and SOD3 found in the ECM. The gene encoding regions for each are found on different chromosomes, which is not surprising seeing as how they have varied effects. SOD1 plays and important role in cell survival and growth; its transcription increases in resonse to heat shock, shear stress, and oxidative stress. Overproduction of TNF-alpha in inflammation is associated with increased oxidative stress and decreased SOD1 expression. SOD2 deficits can lead to increased risk factors for cardiomyopathies. However, proinflammatory cytokines such as TNF-alpha are SOD-2 activatiors. The SOD3 protects cells and the ECM against superoxide anion. Like SOD1, TNF-alpha is an inhibitor of SOD3. I found this very intriguing. Does anybody know why TNF-alpha would act as an SOD2 activator but inhibit the other two?? I did not see anything reguarding this in this article. TNF-alpha overproduction may be the main contributor to increased ROS release in patients with RA, so it is an extremely important part of the mechanisms involved in inflammatory joint diseases. Any insight on this would be great.

So SOD's are very important in inflammation and disease! SOD mimetics are available today. They may attenuate the inflammatory process by decreasing peroxynitrite formation leading to increased availability of NO, decrease the release of proinflammatory cytokines, and/or decrease influx of neutrophils at the sites of inflammation, thus providing a means of relief in several patients! If you have any questions, I'd be happy to answer them.

Happy spring break!!