Roles of Nicotinamide Adenine Dinucleotide (NAD+) in Biological Systems

Poltronieri, Palmiro; Čerekovic, Nataša

doi:10.3390/challe9010003

Cited by 10 publications

(8 citation statements)

References 95 publications

(131 reference statements)

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“…Finally, ADP-ribosyl protein lyase, macrodomain-containing proteins, terminal ADP-ribose protein glycohydrolase 1 (TARG 1) and ARH3 can remove the proximal ADP-ribose residue from the acceptor protein [11][12][13][14] (Figure 1). There are monoADP-ribosylation reaction and polyADP-ribosylation reaction, and they are collectively termed "ADP-ribosylation reaction", catalyzed by enzymes widely found in animals, plants and bacteria using NAD + [15]. However, this article is intended to emphasize the importance of measuring the actual amount of PAR found in vivo and to discuss the methods and the resulting PAR levels in vivo.…”

Section: What Is Polyadp-ribosylation?mentioning

confidence: 99%

“…In 2013, Martello et al reported PAR levels using a modern technique of stable isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) system ( Table 1). They synthesized 13 C, 15 N-labeled PAR from 13 C, 15 N-labeled NAD + and added to the sample as tracer for estimating the recovery of PAR during purification. They reported PAR levels as 0.03 pmol/10 6 PBMC and 0.05-0.1 pmol/10 6 HeLa cells.…”

Section: Measurement Of the Amount Of Par In Vivo (Ie In Cells Or mentioning

confidence: 99%

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In Vivo Level of Poly(ADP-ribose)

et al. 2018

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PolyADP-ribosylation is a post-translational modification that plays key roles in cellular physiological functions and DNA damage responses. PolyADP-ribosylation is finely and dynamically regulated by various enzymes and factors involved in the synthesis and degradation of poly(ADP-ribose) (PAR). To better understand the function of polyADP-ribosylation, it is necessary to quantify and monitor the change of the in vivo level of PAR, the product of polyADP-ribosylation, which is rapidly turning over and kept in quite low level in cells or in organs. Recent developments of potent inhibitors of polyADP-ribosylation is expected to kill BRCA1/2-mutated breast cancer cells and ovarian cancer cells (synthetic lethality). To know the efficacy of these inhibitors in vivo, it is necessary to develop highly sensitive and reproducible methods to know PAR levels within cells or organs. However there have been several difficulties in measuring the physiologically low level of PAR without artefacts. Our experiments recently clarified that the method of sample preparation is very important in addition to the sensitivity and specificity. From reviewing the literature, including ours, we would like to emphasize the importance of the procedures of sample preparation for the assay, in addition to the sensitivity by comparing the reported PAR levels in vivo.

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Section: What Is Polyadp-ribosylation?mentioning

confidence: 99%

Section: Measurement Of the Amount Of Par In Vivo (Ie In Cells Or mentioning

confidence: 99%

In Vivo Level of Poly(ADP-ribose)

et al. 2018

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“…NAD + is a substrate used by enzymes involved in post-translational modifications; in particular, this editorial will focus on ADP ribosylation reactions, producing mono ADP ribose (MAR) and poly ADP ribose (PAR) moieties bound to proteins and nucleic acids [1][2][3]. The intracellular concentration of NAD, its degradation to nicotinamide and its rapid, temporary unavailability (especially into localized energy compartments) are of fundamental importance to cell health or death.…”

Section: Introductionmentioning

confidence: 99%

“…In the effort to have availability of NAD+ for metabolic processes, different subcellular pools of NAD+ are regulated, and free NAD+ levels control signaling by PARPs and redox metabolism [10]. The review provides a clue on the way cells are able to overcome stressful conditions in health and disease, when provided with a surplus of NAD+ [3].…”

Section: Introductionmentioning

confidence: 99%

Emerging Concepts on the Role of ADP-Ribosylation

Poltronieri

2020

Challenges

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NAD + has emerged as a crucial element in both bioenergetic and signaling pathways, since it acts as a key regulator of cellular and organism homeostasis. NAD + is a coenzyme in redox reactions, a donor of adenosine diphosphate-ribose (ADPr) moieties in ADP-ribosylation reactions, and a substrate for sirtuins, a group of histone deacetylase enzymes that use NAD + to remove acetyl groups from proteins. NAD + is also a precursor of cyclic ADP-ribose, a second messenger in the release and signaling of Ca ++ , and of diadenosine tetraphosphate (Ap4A) and oligoadenylates (oligo2 -5 A)-two immune response-activating compounds. In the biological systems considered in this review, NAD + is mostly consumed in ADP-ribose (ADPr) transfer reactions. In this review, the roles of these chemical products are discussed in biological systems, such as in animals, plants, fungi and bacteria. In the review, ADP-ribosylating enzymes are introduced, as well as the importance to restore the NAD + pools in these systems. Finally, a special attention is presently focused on viral macrodomains, aimed to develop inhibitors to improve the immune response to viruses.

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“…Most commonly NAD functions as a redox carrier essential for growth and development. In addition, NAD functions as a signaling molecule during plant stress, inducing defenses in response to plant pathogens 3,4 . In the presence of oxidative stress NAD is readily depleted by consuming enzymes such as PARP and sirtuins to produce NAM 5,6 .…”

Section: Introductionmentioning

confidence: 99%

Nicotinamide Inhibits Aphid Fecundity and Impacts Survival

Sattar

Martinez

Ruiz

et al. 2019

Sci Rep

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Nicotinamide (NAM) alters behavior in C. elegans and Drosophila, serving as an agonist of TRPV channels affecting sensory neurons and mimicking the mode of action of insecticides used to control phloem-feeding insects. The impact of NAM on green peach aphid (Myzus persicae) behaviors was assessed in artificial diet assays and foliar applications to Arabidopsis plants. Aphids feeding on artificial diets supplemented with NAM impaired stylet movement causing feeding interruptions and ultimately starvation and death. Aphid feeding behaviors were negatively impacted on NAM sprayed plants at concentrations as low as 2.5 mM leading to increased mortality. In choice assays with NAM sprayed leaves aphids showed clear preference for untreated control leaves. NAM is an intermediate in the NAD salvage pathway that should accumulate in nicotinamidase (nic) mutants. LC-MS analysis showed NAM accumulates 60-fold in nic-1-1 Arabidopsis mutants as compared with Col-0. Aphid reproductive potential was significantly decreased on nic-1-1 mutant plants, resulting in a smaller colony size and arrested population development. The results support the hypothesis that dietary NAM causes behavioral changes in aphids, including altered feeding, reduced reproduction, and increased mortality. NAM is thought to bind to TRPV channels causing overstimulation of sensory neurons in the aphid feeding apparatus.

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Roles of Nicotinamide Adenine Dinucleotide (NAD+) in Biological Systems

Cited by 10 publications

References 95 publications

In Vivo Level of Poly(ADP-ribose)

In Vivo Level of Poly(ADP-ribose)

Emerging Concepts on the Role of ADP-Ribosylation

Nicotinamide Inhibits Aphid Fecundity and Impacts Survival

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