Browsing by Subject "NAD+"

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    Reduced nicotinamide mononucleotide is a new and potent NAD+ precursor in mammalian cells and mice
    (Wiley, 2021-03-16) Zapata- Pérez, Rubén; Tammaro, Alessandra; Schomakers, Bauke V.; Scantlebery, Angelique M. L.; Denis, Simone; Elfrink, Hyung L.; Giroud- Gerbetant, Judith; Cantó, Carles; López Leonardo, Carmen; McIntyre, Rebecca L.; Weeghel, Michel van; Sánchez Ferrer, Álvaro; Houtkooper, Riekelt H.; Química Orgánica; Bioquímica y Biología Molecular A; Facultad de Química; Facultad de Veterinaria
    Nicotinamide adenine dinucleotide (NAD+) homeostasis is constantly compromised due to degradation by NAD+-dependent enzymes. NAD+ replenishment by supplementation with the NAD+ precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) can alleviate this imbalance. However, NMN and NR are limited by their mild effect on the cellular NAD+ pool and the need of high doses. Here, we report a synthesis method of a reduced form of NMN (NMNH), and identify this molecule as a new NAD+ precursor for the first time. We show that NMNH increases NAD+ levels to a much higher extent and faster than NMN or NR, and that it is metabolized through a different, NRK and NAMPT-independent, pathway. We also demonstrate that NMNH reduces damage and accelerates repair in renal tubular epithelial cells upon hypoxia/reoxygenation injury. Finally, we find that NMNH administration in mice causes a rapid and sustained NAD+ surge in whole blood, which is accompanied by increased NAD+ levels in liver, kidney, muscle, brain, brown adipose tissue, and heart, but not in white adipose tissue. Together, our data highlight NMNH as a new NAD+ precursor with therapeutic potential for acute kidney injury, confirm the existence of a novel pathway for the recycling of reduced NAD+ precursors and establish NMNH as a member of the new family of reduced NAD+ precursors.