The body has evolved a number of ways to protect itself when under stress. One involves the essential trace element selenium and a second depends on a "multi organ protector" that helps defend cells if selenium is absent.
An Irish scientist has helped provide a better understanding of the interplay between selenium and the multi-organ protector protein, Nrf2, as a collaborator on a paper published last month in the Journal of Biological Chemistry.
The body produces a vast array of proteins but selenium is only found in 25 of them, explains Dr Vincent Kelly, a lecturer in Trinity College Dublin's School of Biochemistry and Immunology.
Selenium is an enormously powerful antioxidant, able to protect cells from the damage caused by free oxygen. Many people have diets that are low in selenium however and taking the cholesterol- reducing statin drugs can also inhibit selenium levels in the body.
Kelly and collaborator Takafumi Suzuki of the University of Tsukuba and colleagues studied what happens if selenium levels drop or go missing entirely. "Many of these proteins are involved in oxidative stress and cell damage," says Kelly, who is now an investigator funded by Science Foundation Ireland. "We could show that they were essential for life and demonstrated how important these proteins are as antioxidants."
Yet when selenium goes missing, the cells can rely on another protective system to keep oxidative damage in check based on the protein Nrf2.
The Nrf2 system kicks in immediately to counter oxidative stress. The Nrf2 protein acts as a sensor to detect damage, can tune the protective action up or down depending on the amount of damage and can shut it off when the cause of stress has disappeared, Kelly explains.
It works in conjunction with the selenoproteins to block free oxygen damage, but can moderate its activity based on the chemistry within the cell. "The reason why the Nrf2 system is so important is it is inducible and regulatable. It can sense a signal, amplify the signal and then switch it off again."
The Nrf2 protein is a "transcription factor", a protein that can bind directly to the DNA in a cell's nucleus. Once in place it acts like a switch to turn on production of many other proteins, which in the case of Nrf2 act to dampen down oxidative damage.
The research group was able to show that if the selenoproteins were at low ebb or absent, cells could still depend on the protective action of the Nrf2 system. "There are two layers of protection. Selenium provides baseline protection while the Nrf2 is important as an induced extra layer of protection," Kelly says.
The results suggest that the Nrf2 system serves as a rapid response to oxidative stress, or as a replacement if selenium levels are too low.
The Nrf2 pathway is very highly conserved and is found in a wide range of species from humans to the fruit fly. Yet the current belief is that the selenium-based system is even more ancient and goes back much further into our evolutionary past, Kelly says. It is even found in some bacteria, suggesting a very early use of selenium as an antioxidant inside the cell.
