Standard

Purine nucleoside phosphorylase controls nicotinamide riboside metabolism in mammalian cells. / Kropotov, Andrey ; Kulikova, Veronika; Solovjeva, Ljudmila; Yakimov1, Alexander; Nerinovski, Kirill; Svetlova, Maria; Sudnitsyna, Julia; Plusnina, Alena; Antipova, Maria; Khodorkovskiy, Mikhail; Migaud, Marie E. ; Gambaryan, Stepan; Ziegler, Mathias; Nikiforov, Andrey.

в: Journal of Biological Chemistry, Том 298, № 12, 102615, 01.12.2022.

Результаты исследований: Научные публикации в периодических изданияхстатьяРецензирование

Harvard

Kropotov, A, Kulikova, V, Solovjeva, L, Yakimov1, A, Nerinovski, K, Svetlova, M, Sudnitsyna, J, Plusnina, A, Antipova, M, Khodorkovskiy, M, Migaud, ME, Gambaryan, S, Ziegler, M & Nikiforov, A 2022, 'Purine nucleoside phosphorylase controls nicotinamide riboside metabolism in mammalian cells', Journal of Biological Chemistry, Том. 298, № 12, 102615. https://doi.org/10.1016/j.jbc.2022.102615

APA

Kropotov, A., Kulikova, V., Solovjeva, L., Yakimov1, A., Nerinovski, K., Svetlova, M., Sudnitsyna, J., Plusnina, A., Antipova, M., Khodorkovskiy, M., Migaud, M. E., Gambaryan, S., Ziegler, M., & Nikiforov, A. (2022). Purine nucleoside phosphorylase controls nicotinamide riboside metabolism in mammalian cells. Journal of Biological Chemistry, 298(12), [102615]. https://doi.org/10.1016/j.jbc.2022.102615

Vancouver

Kropotov A, Kulikova V, Solovjeva L, Yakimov1 A, Nerinovski K, Svetlova M и пр. Purine nucleoside phosphorylase controls nicotinamide riboside metabolism in mammalian cells. Journal of Biological Chemistry. 2022 Дек. 1;298(12). 102615. https://doi.org/10.1016/j.jbc.2022.102615

Author

Kropotov, Andrey ; Kulikova, Veronika ; Solovjeva, Ljudmila ; Yakimov1, Alexander ; Nerinovski, Kirill ; Svetlova, Maria ; Sudnitsyna, Julia ; Plusnina, Alena ; Antipova, Maria ; Khodorkovskiy, Mikhail ; Migaud, Marie E. ; Gambaryan, Stepan ; Ziegler, Mathias ; Nikiforov, Andrey. / Purine nucleoside phosphorylase controls nicotinamide riboside metabolism in mammalian cells. в: Journal of Biological Chemistry. 2022 ; Том 298, № 12.

BibTeX

@article{efdce76e39dd487d81d22fddcf06df11,
title = "Purine nucleoside phosphorylase controls nicotinamide riboside metabolism in mammalian cells",
abstract = "Nicotinamide riboside (NR) is an effective precursor of nicotinamide adenine dinucleotide (NAD) in human and animal cells. NR supplementation can increase the level of NAD in various tissues and thereby improve physiological functions that are weakened or lost in experimental models of aging or various human pathologies. However, there are also reports questioning the efficacy of NR supplementation. Indeed, the mechanisms of its utilization by cells are not fully understood. Herein, we investigated the role of purine nucleoside phosphorylase (PNP) in NR metabolism in mammalian cells. Using both PNP overexpression and genetic knockout, we show that after being imported into cells by members of the equilibrative nucleoside transporter family, NR is predominantly metabolized by PNP, resulting in nicotinamide (Nam) accumulation. Intracellular cleavage of NR to Nam is prevented by the potent PNP inhibitor Immucillin H in various types of mammalian cells. In turn, suppression of PNP activity potentiates NAD synthesis from NR. Combining pharmacological inhibition of PNP with NR supplementation in mice, we demonstrate that the cleavage of the riboside to Nam is strongly diminished, maintaining high levels of NR in blood, kidney and liver. Moreover, we show that PNP inhibition stimulates Nam mononucleotide and NAD+ synthesis from NR in vivo, in particular, in the kidney. Thus, we establish PNP as a major regulator of NR metabolism in mammals and provide evidence that the health benefits of NR supplementation could be greatly enhanced by concomitant downregulation of PNP activity.",
keywords = "NAD biosynthesis, human, metabolism, mouse, nicotinamide adenine dinucleotide (NAD), nicotinamide riboside, purine nucleoside phosphorylase",
author = "Andrey Kropotov and Veronika Kulikova and Ljudmila Solovjeva and Alexander Yakimov1 and Kirill Nerinovski and Maria Svetlova and Julia Sudnitsyna and Alena Plusnina and Maria Antipova and Mikhail Khodorkovskiy and Migaud, {Marie E.} and Stepan Gambaryan and Mathias Ziegler and Andrey Nikiforov",
note = "Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = dec,
day = "1",
doi = "10.1016/j.jbc.2022.102615",
language = "English",
volume = "298",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "12",

}

RIS

TY - JOUR

T1 - Purine nucleoside phosphorylase controls nicotinamide riboside metabolism in mammalian cells

AU - Kropotov, Andrey

AU - Kulikova, Veronika

AU - Solovjeva, Ljudmila

AU - Yakimov1, Alexander

AU - Nerinovski, Kirill

AU - Svetlova, Maria

AU - Sudnitsyna, Julia

AU - Plusnina, Alena

AU - Antipova, Maria

AU - Khodorkovskiy, Mikhail

AU - Migaud, Marie E.

AU - Gambaryan, Stepan

AU - Ziegler, Mathias

AU - Nikiforov, Andrey

N1 - Publisher Copyright: © 2022 The Authors

PY - 2022/12/1

Y1 - 2022/12/1

N2 - Nicotinamide riboside (NR) is an effective precursor of nicotinamide adenine dinucleotide (NAD) in human and animal cells. NR supplementation can increase the level of NAD in various tissues and thereby improve physiological functions that are weakened or lost in experimental models of aging or various human pathologies. However, there are also reports questioning the efficacy of NR supplementation. Indeed, the mechanisms of its utilization by cells are not fully understood. Herein, we investigated the role of purine nucleoside phosphorylase (PNP) in NR metabolism in mammalian cells. Using both PNP overexpression and genetic knockout, we show that after being imported into cells by members of the equilibrative nucleoside transporter family, NR is predominantly metabolized by PNP, resulting in nicotinamide (Nam) accumulation. Intracellular cleavage of NR to Nam is prevented by the potent PNP inhibitor Immucillin H in various types of mammalian cells. In turn, suppression of PNP activity potentiates NAD synthesis from NR. Combining pharmacological inhibition of PNP with NR supplementation in mice, we demonstrate that the cleavage of the riboside to Nam is strongly diminished, maintaining high levels of NR in blood, kidney and liver. Moreover, we show that PNP inhibition stimulates Nam mononucleotide and NAD+ synthesis from NR in vivo, in particular, in the kidney. Thus, we establish PNP as a major regulator of NR metabolism in mammals and provide evidence that the health benefits of NR supplementation could be greatly enhanced by concomitant downregulation of PNP activity.

AB - Nicotinamide riboside (NR) is an effective precursor of nicotinamide adenine dinucleotide (NAD) in human and animal cells. NR supplementation can increase the level of NAD in various tissues and thereby improve physiological functions that are weakened or lost in experimental models of aging or various human pathologies. However, there are also reports questioning the efficacy of NR supplementation. Indeed, the mechanisms of its utilization by cells are not fully understood. Herein, we investigated the role of purine nucleoside phosphorylase (PNP) in NR metabolism in mammalian cells. Using both PNP overexpression and genetic knockout, we show that after being imported into cells by members of the equilibrative nucleoside transporter family, NR is predominantly metabolized by PNP, resulting in nicotinamide (Nam) accumulation. Intracellular cleavage of NR to Nam is prevented by the potent PNP inhibitor Immucillin H in various types of mammalian cells. In turn, suppression of PNP activity potentiates NAD synthesis from NR. Combining pharmacological inhibition of PNP with NR supplementation in mice, we demonstrate that the cleavage of the riboside to Nam is strongly diminished, maintaining high levels of NR in blood, kidney and liver. Moreover, we show that PNP inhibition stimulates Nam mononucleotide and NAD+ synthesis from NR in vivo, in particular, in the kidney. Thus, we establish PNP as a major regulator of NR metabolism in mammals and provide evidence that the health benefits of NR supplementation could be greatly enhanced by concomitant downregulation of PNP activity.

KW - NAD biosynthesis

KW - human

KW - metabolism

KW - mouse

KW - nicotinamide adenine dinucleotide (NAD)

KW - nicotinamide riboside

KW - purine nucleoside phosphorylase

UR - https://linkinghub.elsevier.com/retrieve/pii/S0021925822010584

UR - https://www.mendeley.com/catalogue/8243261c-71c8-3b33-979d-b3c832a15af3/

UR - http://www.scopus.com/inward/record.url?scp=85141795200&partnerID=8YFLogxK

U2 - 10.1016/j.jbc.2022.102615

DO - 10.1016/j.jbc.2022.102615

M3 - Article

C2 - 36265580

VL - 298

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 12

M1 - 102615

ER -

ID: 99501151