Study Finds Protecting Skin Cells from UV Damage Depends on NMN Synthesis

Study Finds Protecting Skin Cells from UV Damage Depends on NMN Synthesis

Our cells depend on nicotinamide adenine dinucleotide (NAD+) to function and survive. Drops in NAD+ levels caused by aging are linked to diseases like metabolic disorders, cancer, and neurodegenerative conditions. Similar to aging, harmful UV rays from the sun can also trigger NAD+ depletion. Understanding how these NAD+ depleting phenomena work and can be prevented or reversed has become a hot topic in research. 

Tsuji-Naito and colleagues from the DHC Corporation Laboratories in Japan published a study in the Journal of Photochemistry and Photobiology showing that UV damage activates NAD+ synthesis and NAD+ consuming enzymes in a balancing act that determines survival or dysfunction for human skin cells. They show that, in a tug of war, UV radiation activates nicotinamide phosphoribosyltransferase (NAMPT) to produce the NAD+ precursor nicotinamide mononucleotide (NMN) and also activates the NAD+ consuming enzyme poly ADP-ribose polymerase (PARP). If NAD+ synthesis falters during this balancing act, PARP will severely deplete NAD+ levels, which can trigger skin cell proliferation arrest and dysfunction. Interestingly, blocking NAMPT’s NAD+ production lets PARP drain NAD+, but supplementing with the NAD+ precursors NMN (100 µM) or nicotinamide riboside (NR; 50 µM) restores the cells’ abilities to recover from UV damage.

 

NAMPT Generates NAD+ to Promote Cell Energy Production and Viability

Since NAMPT generates NAD+’s precursor NMN, Tsuji-Naito and colleagues wanted to test whether this NMN-producing enzyme restores UV-induced NAD+ depletion. They applied the NAMPT inhibitor FK866 to UV-irradiated cells and found that it led to severe NAD+ deficiencies. Moreover, getting rid of NAMPT activity eliminates the recovery of NAD+ levels after UV damage, indicating that NAMPT plays a crucial role in maintaining NAD+ levels to counteract PARP.

Tsuji-Naito and colleagues then tested the effects of UV rays on NAMPT activity, finding that irradiation of skin cells drove NAMPT enzyme function up to almost three times its original activity eight hours after UV damage. The stimulation of NAMPT activity affected cell health by promoting energy production in the face of UV damage. However, blocking NAMPT function during UV radiation diminished cell viability by about 35%, indicating that NAMPT acts to maintain cell health and survival after UV damage.

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