Ultraviolet radiation increases skin damage by generating Reactive Oxygen Species (ROS) and Reactive Carbonyl Species (RCS). The Broad Institute Gene Pattern found GHK to increase the activity of the SRRR2C human gene 8.2-fold. It produces a small, proline-rich, anti-oxidant protein that protects outer skin cells from oxidative damage from Reactive Oxygen Species (ROS). When the ROS level is low, the protein remains in the outer cell membrane but when the ROS level is high, the protein clusters around the cell's DNA to protect it.
Vermeij WP, Florea BI, Isenia S, Alia A, Brouwer J, Backendorf C. PROTEOMIC IDENTIFICATION OF IN VIVO INTERACTORS REVEALS NOVEL FUNCTION OF SKIN CORNIFICATION PROTEINS, J Proteome Res. 2012 Apr 23.
Protection against injurious external insults and loss of vital fluids is essential for life and is in all organisms, from bacteria to plants and humans, provided by some form of barrier.
Members of the small-proline-rich (SPRR) protein family are major components of the cornified cell envelope (CE), a structure responsible for the barrier properties of our skin.
These proteins are efficient reactive oxygen species (ROS) quenchers involved not only in the establishment of the skin's barrier function but also in cell migration and wound healing.
Here, a proteomic analysis of in-vivo SPRR-interacting proteins confirmed their function in CE-formation and ROS-quenching and also revealed a novel unexpected role in DNA-binding.
Direct in-vitro and in-vivo evidence proved that the DNA-binding capacity of SPRRs is regulated by the oxidation state of the proteins.
At low ROS levels, nuclear SPRR is able to bind DNA and prevent ROS-induced DNA damage. When ROS levels increase SPRR proteins multimerize and form an effective antioxidant barrier at the cell periphery, possibly to prevent the production or infiltration of ROS.
At even higher ROS exposure DNA-binding is restituted. A molecular model explaining how the intracellular oxidation state of SPRRs likely influences their selective protective function is provided.
Vermeij WP, Alia A, Backendorf C. ROS quenching potential of the epidermal cornified cell envelope. J Invest Dermatol. 2011 Jul;131(7):1435-41.
The cornified cell envelope (CE) is a specialized structure assembled beneath the plasma membrane of keratinocytes in the outermost layers of the epidermis.
It is essential for the physical and permeability properties of the barrier function of the skin. Our skin is continuously exposed to atmospheric oxygen and threatened by reactive oxygen species (ROS).
Here, we identify the CE as a first line of antioxidant defense and show that the small proline-rich (SPRR) family of CE precursor proteins have a major role in ROS detoxification.
Cysteine residues within these proteins are responsible for ROS quenching, resulting in inter- and intramolecular S-S bond formation, both in isolated proteins and purified CEs. The related keratinocyte proline-rich protein is also oxidized on several cysteine residues within the CE.
Differences in antioxidant potential between various SPRR family members are likely determined by structural differences rather than by the amount of cysteine residues per protein.
Loricrin, a major component of the CE with a higher cysteine content than SPRRs, is a weak ROS quencher and oxidized on a single cysteine residue within the CE. It is inferred that SPRR proteins provide the outermost layer of our skin with a highly adaptive and protective antioxidant shield.