A skin pigmentation mechanism that can darken the color of human skin as a natural defense against ultraviolet (UV)-associated cancers has been discovered by scientists. Mediating the biological process is an enzyme, NNT, which plays a key role in the production of melanin (a pigment that protects the skin from harmful UV rays) and whose inhibition through a topical drug or ointment could potentially reduce the risk of skin cancers. The study was published online in Cell.
"Skin pigmentation and its regulation are critically important because pigments confer major protection against UV-related cancers of the skin, which are the most common malignancies found in humans," says senior and co-corresponding author. "Darker-pigmented individuals are better protected from cancer-causing UV radiation by the light-scattering and antioxidant properties of melanin, while people with the fairest and lightest skin are at highest risk of developing skin cancers."
Through their laboratory work with skin from humans and animal models, the researchers mimicked the natural protection that exists in people with dark pigments. In the process, they gained a fuller understanding of the biochemical mechanism involved along with their drivers, and how they might be influenced by a topical agent independent of UV radiation, sun exposure, or genetics.
"We had assumed that the enzymes that make melanin by oxidizing the amino acid tyrosine in the melanosome (the synthesis and storage compartment of the cell) are largely regulated by gene expression," explains the author. They were surprised to learn, however, that the amount of melanin being produced is in large part regulated by a much different chemical mechanism, one that can ultimately be traced to an enzyme in the mitochondria, the inner chamber of the cell, with the ability to alter skin pigmentation.
That enzyme is nicotinamide nucleotide transhydrogenase, or NNT. Researchers found that topical application of small molecule inhibitors of NNT resulted in skin darkening in human skin, and that mice with decreased NNT function displayed increased fur pigmentation. To test their discovery, they challenged the skin with UV radiation and found that the skin with darker pigments was indeed protected from DNA damage inflicted by ultraviolet rays.
"We're excited by the discovery of a distinct pigmentation mechanism because it could pave the way, after additional studies and safety assessments, for a new approach to skin darkening and protection by targeting NNT," says the lead author and co-corresponding author of the study. "The overarching goal, of course, is to improve skin cancer prevention strategies and to offer effective new treatment options to the millions of people suffering from pigmentary disorders."
https://www.cell.com/cell/fulltext/S0092-8674(21)00757-1
A redox-dependent skin pigmentation mechanism identified!
- 1,586 views
- Added
Edited
Latest News
Chromatin and RNA interacti…
By newseditor
Posted 18 May
Why patients with ARID1A mu…
By newseditor
Posted 18 May
Smuggling small molecule mo…
By newseditor
Posted 18 May
Men with gene mutations are…
By newseditor
Posted 17 May
B cell oxidative phosphoryl…
By newseditor
Posted 17 May
Other Top Stories
An immune cell enzyme in the defense against tuberculosis
Read more
Protocadherin-1is an hantavirus receptor
Read more
Sugar and microbiome in mother's milk influences neonatal rotavirus…
Read more
How antibiotics help spread resistance
Read more
A new mechanism to increase Trypanosoma parasite virulence
Read more
Protocols
Breast cancer-on-chip for p…
By newseditor
Posted 16 May
Methods for making and obse…
By newseditor
Posted 15 May
Mime-seq 2.0: a method to s…
By newseditor
Posted 13 May
Improved detection of DNA r…
By newseditor
Posted 09 May
Single-cell adhesive profil…
By newseditor
Posted 07 May
Publications
Immunotherapy for colorecta…
By newseditor
Posted 18 May
Single-cell multiplex chrom…
By newseditor
Posted 18 May
Autophagy preferentially de…
By newseditor
Posted 18 May
Poison Ivy, Poison Oak, and…
By newseditor
Posted 18 May
GLP-1-directed NMDA recepto…
By newseditor
Posted 18 May
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar