Equilibrative Nucleoside Transporters Mediate the Import of Nicotinamide Riboside and Nicotinic Acid Riboside into Human Cells
| Autor: | Andrey Kropotov, Mathias Ziegler, Andrey Nikiforov, Alexander Yakimov, L. V. Solovjeva, Kirill Nerinovski, Mikhail Khodorkovskiy, Marie E. Migaud, Julia Sudnitsyna, Maria Svetlova, Veronika Kulikova |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Niacinamide
Aging Magnetic Resonance Spectroscopy NAD+ metabolism Pyridinium Compounds Nicotinamide adenine dinucleotide Article Catalysis Inorganic Chemistry lcsh:Chemistry chemistry.chemical_compound Cytosol Equilibrative Nucleoside Transport Proteins Humans Metabolomics Phosphorylation Physical and Theoretical Chemistry Molecular Biology lcsh:QH301-705.5 Nicotinamide Mononucleotide Spectroscopy concentrative nucleoside transporters nicotinamide riboside human cells Organic Chemistry HEK 293 cells Membrane Transport Proteins Equilibrative nucleoside transporter General Medicine Riboside NAD Recombinant Proteins Computer Science Applications Phosphotransferases (Alcohol Group Acceptor) HEK293 Cells Biochemistry chemistry lcsh:Biology (General) lcsh:QD1-999 nicotinic acid riboside equilibrative nucleoside transporters Nicotinamide riboside Ribonucleosides NAD+ kinase Nucleoside |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 1391, p 1391 (2021) International Journal of Molecular Sciences Volume 22 Issue 3 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Nicotinamide riboside (NR), a new form of vitamin B3, is an effective precursor of nicotinamide adenine dinucleotide (NAD+) in human and animal cells. The introduction of NR into the body effectively increases the level of intracellular NAD+ and thereby restores physiological functions that are weakened or lost in experimental models of aging and various pathologies. Despite the active use of NR in applied biomedicine, the mechanism of its transport into mammalian cells is currently not understood. In this study, we used overexpression of proteins in HEK293 cells, and metabolite detection by NMR, to show that extracellular NR can be imported into cells by members of the equilibrative nucleoside transporter (ENT) family ENT1, ENT2, and ENT4. After being imported into cells, NR is readily metabolized resulting in Nam generation. Moreover, the same ENT-dependent mechanism can be used to import the deamidated form of NR, nicotinic acid riboside (NAR). However, NAR uptake into HEK293 cells required the stimulation of its active utilization in the cytosol such as phosphorylation by NR kinase. On the other hand, we did not detect any NR uptake mediated by the concentrative nucleoside transporters (CNT) CNT1, CNT2, or CNT3, while overexpression of CNT3, but not CNT1 or CNT2, moderately stimulated NAR utilization by HEK293 cells. |
| Databáze: | OpenAIRE |
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