Regulation of intracellular levels of NAD: A novel role for CD38

Aksoy, Pınar; White, Thomas A.; Thompson, Michael A.; Chini, Eduardo N.

doi:10.1016/j.bbrc.2006.05.042

Cited by 290 publications

(331 citation statements)

References 29 publications

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“…To determine the mechanism and signaling pathways accounting for the induction of NAD + /NADH levels and SIRT3 by RGS14 deficiency, we investigated the CD38 level in skeletal muscle, which is the primary NADase in mammals and regulates cellular levels of NAD (Aksoy, White, Thompson & Chini, 2006; Camacho‐Pereira et al., 2016; Young, Choleris, Lund & Kirkland, 2006). Decreased CD38 level in RGS14 KO (Figure 3b) was found ( n = 6–7/group), supporting the increased NAD + level in Figure 3a.…”

Section: Resultsmentioning

confidence: 99%

Enhanced longevity and metabolism by brown adipose tissue with disruption of the regulator of G protein signaling 14

et al. 2018

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SummaryDisruption of the regulator for G protein signaling 14 (RGS14) knockout (KO) in mice extends their lifespan and has multiple beneficial effects related to healthful aging, that is, protection from obesity, as reflected by reduced white adipose tissue, protection against cold exposure, and improved metabolism. The observed beneficial effects were mediated by improved mitochondrial function. But most importantly, the main mechanism responsible for the salutary properties of the RGS14 KO involved an increase in brown adipose tissue (BAT), which was confirmed by surgical BAT removal and transplantation to wild‐type (WT) mice, a surgical simulation of a molecular knockout. This technique reversed the phenotype of the RGS14 KO and WT, resulting in loss of the improved metabolism and protection against cold exposure in RGS14 KO and conferring this protection to the WT BAT recipients. Another mechanism mediating the salutary features in the RGS14 KO was increased SIRT3. This mechanism was confirmed in the RGS14 X SIRT3 double KO, which no longer demonstrated improved metabolism and protection against cold exposure. Loss of function of the Caenorhabditis elegans RGS‐14 homolog confirmed the evolutionary conservation of this mechanism. Thus, disruption of RGS14 is a model of healthful aging, as it not only enhances lifespan, but also protects against obesity and cold exposure and improves metabolism with a key mechanism of increased BAT, which, when removed, eliminates the features of healthful aging.

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Section: Resultsmentioning

confidence: 99%

Enhanced longevity and metabolism by brown adipose tissue with disruption of the regulator of G protein signaling 14

et al. 2018

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“…S3, the methodology used in this study was sensitive to small variations in NAD ϩ concentration. Furthermore, we have previously detected changes in NAD ϩ and NAD ϩ metabolites in several cells and tissues using the same method (10,11,14,31,(55)(56)(57). Taken together, these results demonstrate that AMPK can activate SIRT1 without detectable changes in cellular NAD ϩ levels.…”

Section: Resultsmentioning

confidence: 99%

Role of Deleted in Breast Cancer 1 (DBC1) Protein in SIRT1 Deacetylase Activation Induced by Protein Kinase A and AMP-activated Protein Kinase

Nin

Escande

Chini

et al. 2012

Journal of Biological Chemistry

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Background: DBC1 is a key regulator of SIRT1 activity, although it is unknown how the SIRT1-DBC1 interaction is regulated. Results: PKA and AMPK activate SIRT1 by disrupting the interaction between SIRT1 and DBC1. Conclusion: We provide mechanistic evidence on how the SIRT1-DBC1 complex is regulated. Significance: The SIRT1-DBC1 complex constitutes a target for the development of drugs to activate SIRT1.

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“…This observation, however, does not exclude its production. In both mouse and rat livers, cyclic-ADP-ribose is probably produced in very small amounts compared to ADP-ribose -only one molecule of cADP-ribose is generated intracellularly for every 100 molecules of NAD + that are hydrolyzed [15] . Furthermore, cADPribose probably does not permeate the cell membrane, so that it cannot be expected to appear in the outflowing perfusate.…”

Section: Discussionmentioning

confidence: 99%

Transformation and action of extracellular NAD+ in perfused rat and mouse livers

Broetto-Biazon

Bracht

et al. 2008

Acta Pharmacol Sin

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Aim: Transformation and possible metabolic effects of extracellular NAD + were investigated in the livers of mice (Mus musculus; Swiss strain) and rats (Rattus novergicus; Holtzman and Wistar strains). Methods: The livers were perfused in an open system using oxygen-saturated Krebs/Henseleit-bicarbonate buffer (pH 7.4) as the perfusion fluid. The transformation of NAD + was monitored using high-performance liquid chromatography. Results: In the mouse liver, the single-pass metabolism of 100 µmol/L NAD + was almost complete; ADP-ribose and nicotinamide were the main products in the outflowing perfusate. In the livers of both Holtzman and Wistar rats, the main transformation products were ADP-ribose, uric acid and nicotinamide; significant amounts of inosine and AMP were also identified. On a weight basis, the transformation of NAD + was more efficient in the mouse liver. In the rat liver, 100 µmol/L NAD + transiently inhibited gluconeogenesis and oxygen uptake. Inhibition was followed by a transient stimulation. Inhibition was more pronounced in the Wistar strain and stimulation was more pronounced in the Holtzman strain. In the mouse liver, no clear effects on gluconeogenesis and oxygen uptake were found even at 500 µmol/L NAD + . Conclusion:It can be concluded that the functions of extracellular NAD + are species-dependent and that observations in one species are strictly valid for that species. Interspecies extrapolations should thus be made very carefully. Actually, even variants of the same species can demonstrate considerably different responses.

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Regulation of intracellular levels of NAD: A novel role for CD38

Cited by 290 publications

References 29 publications

Enhanced longevity and metabolism by brown adipose tissue with disruption of the regulator of G protein signaling 14

Enhanced longevity and metabolism by brown adipose tissue with disruption of the regulator of G protein signaling 14

Role of Deleted in Breast Cancer 1 (DBC1) Protein in SIRT1 Deacetylase Activation Induced by Protein Kinase A and AMP-activated Protein Kinase

Transformation and action of extracellular NAD+ in perfused rat and mouse livers

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