Nicotinamide riboside Induced Energy Stress and Metabolic Reprogramming in BEAS-2B Cells

Nicotinamide riboside
(NR), a NAD+ precursor, has received
attention due to several health benefits it has induced in experimental
models. Studies in cultured cells, animals, and humans consistently
show increased NAD+ availability after NR supplementation,
which is considered the only mode of NR action that leads to health
benefits. In the present study, we show that a persistently low NR
concentration (1 μM) in the growth medium of BEAS-2B human cells,
grown in a monolayer, induces energy stress, which precedes a cellular
NAD+ increase after 192 h. NR concentrations greater than
1 μM under the specified conditions were cytotoxic in the 2D
cell culture model, while all concentrations tested in the 3D cell
culture model (BEAS-2B cell spheroids exposed to 1, 5, 10, and 50
μM NR) induced apoptosis. Shotgun proteomics revealed that NR
modulated the abundance of proteins, agreeing with the observed effects
on cellular energy metabolism and cell growth or survival. Energy
stress may activate pathways that lead to health benefits such as
cancer prevention. Accordingly, the premalignant 1198 cell line was
more sensitive to NR cytotoxicity than the phenotypically normal parent
BEAS-2B cell line. The role of a mild energy stress induced by low
concentrations of NR in its beneficial effects deserves further investigation.
On the other hand, strategies to increase the bioavailability of NR
require attention to toxic effects that may arise.