According to an article in ScienceDaily, researchers have found that the protein Nrf2 plays a fundamental role in tissue repair and in the prevention of cancer development. Cell biologists from ETH Zurich have discovered that this molecular switch prevents cell damage in the skin caused by UVB rays from sunlight.
UVB rays are commonly known to influence the development of skin cancer. The rays can damage DNA directly or induce the formation of oxygen radicals, which in turn damage the cell membrane or can attack and damage the strands of DNA. If the cell fails to repair the genetic material in time, it accumulates damaged DNA, and can frequently result in skin cancer.
The skin, however, still has natural defenses against UVB rays. Cells in the outermost layer of the skin, called keratinocytes, have the ability to repair or even prevent damage to the DNA, proteins and membranes. The Nrf2 protein was previously recognized as an important factor in the wound-healing process and plays a key protective role in many stress situations. Recently, however, researchers at ETH Zurich identified Nrf2 as a key factor in the skin’s response to UVB radiation.
Nrf2 is a protein “switch” that will stimulate certain genes in a cell in specific, predefined situations. For example, when skin is exposed to UVB or UVA from the sun’s rays, the skin is automatically protected by actions taken by the cells when their genes receive a “message” from the Nrf2 protein. There’s also a molecule in the cells that harnesses free radicals and, essentially, destroys their power to wreak havoc on the cells. That molecule is called GSH, or glutathione.
The scientists also observed that the concentration and activity of the Nrf2 protein in the skin decreases the further from the surface it gets. This means the innermost skin layers die more quickly with exposure to UVB than the outer ones.
This is a paradox, considering that you would expect the layers of skin with the most UVB exposure to die sooner than the inner cells, especially since those cells have to produce new skin cells through countless divisions.
Nevertheless, the study explains why the apparent paradox makes sense: Since it is imperative for the epidermis’ integrity to stay intact, there are higher levels of Nrf2 in this layer. However, the innermost layers of skin are made up of stem cells. These stem cells must multiply in order to create new layers of skin. If the stem cells come in contact with UVB rays that cause extensive damage, those stem cells will die in order to prevent the damage from being passed to the offspring. If UVB radiation hits the skin, however, the level of protection in the inner layer is not sufficient and the cells die before too much damage can accumulate. When your skin ages from sun damage, it is not just the epidermis that may have damage but multiple layers of your skin.
A previous study showed that broccoli-sprout extracts can protect the skin from UVB toxicity. The extract contains sulforaphane, a substance which activates Nrf2. The scientists at ETH Zurich were able to link the two together to create a strategy to limit skin damage caused by UVB radiation.
“This mechanism is interesting as it could be used for pharmacologic intervention,” says Matthias Schäfer, one of the participating scientists. However, there are many factors to further research before Nrf2 stimulators can be commercially introduced for sun protection. Scientists must figure out how strongly and how often Nrf2 can be activated and what side effects this activation has. Although observations in lab mice revealed that the skin becomes flaky upon increased activation of Nrf2, this breakthrough suggests that the development Nrf2 activators could constitute an important strategy in the protection against UV damage.
