Reduced nicotinamide mononucleotide is a new and potent NAD + precursor in mammalian cells and mice.

Autor: Zapata-Pérez R; Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Tammaro A; Pathology Department, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Schomakers BV; Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Core Facility Metabolomics, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Scantlebery AML; Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Denis S; Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Elfrink HL; Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Core Facility Metabolomics, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Giroud-Gerbetant J; Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland., Cantó C; Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland., López-Leonardo C; Department of Organic Chemistry, University of Murcia, Murcia, Spain., McIntyre RL; Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., van Weeghel M; Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Core Facility Metabolomics, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Sánchez-Ferrer Á; Department of Biochemistry and Molecular Biology-A, University of Murcia, Murcia, Spain., Houtkooper RH; Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2021 Apr; Vol. 35 (4), pp. e21456.
DOI: 10.1096/fj.202001826R
Abstrakt: 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.
(© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
Externí odkaz: