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      NAD +, Sirtuins and PARPs: enhancing oocyte developmental competence

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          Abstract

          Oocyte quality is the limiting factor in female fertility. It is well known that maternal nutrition plays a role in reproductive function, and manipulating nutrition to improve fertility in livestock has been common practice in the past, particularly with respect to negative energy balance in cattle. A deficiency in nicotinamide adenine dinucleotide (NAD +) production has been associated with increased incidences of miscarriage and congenital defects in humans and mice, while elevating NAD + through dietary supplements in aged subjects improved oocyte quality and embryo development. NAD + is consumed by Sirtuins and poly-ADP-ribose polymerases (PARPs) within the cell and thus need constant replenishment in order to maintain various cellular functions. Sirtuins and PARPs play important roles in oocyte maturation and embryo development, and their activation may prove beneficial to in vitro embryo production and livestock breeding programs. This review examines the roles of NAD +, Sirtuins and PARPs in aspects of fertility, providing insights into the potential use of NAD +-elevating treatments in livestock breeding and embryo production programs.

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          Sir2 mediates longevity in the fly through a pathway related to calorie restriction.

          Blanka Rogina, Stephen L. Helfand (2004)
          Calorie restriction can extend life span in a variety of species including mammals, flies, nematodes, and yeast. Despite the importance of this nearly universal effect, little is understood about the molecular mechanisms that mediate the life-span-extending effect of calorie restriction in metazoans. Sir2 is known to be involved in life span determination and calorie restriction in yeast mother cells. In nematodes increased Sir2 can extend life span, but a direct link to calorie restriction has not been demonstrated. We now report that Sir2 is directly involved in the calorie-restriction life-span-extending pathway in Drosophila. We demonstrate that an increase in Drosophila Sir2 (dSir2) extends life span, whereas a decrease in dSir2 blocks the life-span-extending effect of calorie reduction or rpd3 mutations. These data lead us to propose a genetic pathway by which calorie restriction extends life span and provides a framework for genetic and pharmacological studies of life span extension in metazoans.
          Article 0 comments Cited 313 times – based on 0 reviews     Review now
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            The redox state of free nicotinamide-adenine dinucleotide in the cytoplasm and mitochondria of rat liver.

            D Williamson, P. Lund, H KREBS (1967)
            1. The concentrations of the oxidized and reduced substrates of the lactate-, beta-hydroxybutyrate- and glutamate-dehydrogenase systems were measured in rat livers freeze-clamped as soon as possible after death. The substrates of these dehydrogenases are likely to be in equilibrium with free NAD(+) and NADH, and the ratio of the free dinucleotides can be calculated from the measured concentrations of the substrates and the equilibrium constants (Holzer, Schultz & Lynen, 1956; Bücher & Klingenberg, 1958). The lactate-dehydrogenase system reflects the [NAD(+)]/[NADH] ratio in the cytoplasm, the beta-hydroxybutyrate dehydrogenase that in the mitochondrial cristae and the glutamate dehydrogenase that in the mitochondrial matrix. 2. The equilibrium constants of lactate dehydrogenase (EC 1.1.1.27), beta-hydroxybutyrate dehydrogenase (EC 1.1.1.30) and malate dehydrogenase (EC 1.1.1.37) were redetermined for near-physiological conditions (38 degrees ; I0.25). 3. The mean [NAD(+)]/[NADH] ratio of rat-liver cytoplasm was calculated as 725 (pH7.0) in well-fed rats, 528 in starved rats and 208 in alloxan-diabetic rats. 4. The [NAD(+)]/[NADH] ratio for the mitochondrial matrix and cristae gave virtually identical values in the same metabolic state. This indicates that beta-hydroxybutyrate dehydrogenase and glutamate dehydrogenase share a common pool of dinucleotide. 5. The mean [NAD(+)]/[NADH] ratio within the liver mitochondria of well-fed rats was about 8. It fell to about 5 in starvation and rose to about 10 in alloxan-diabetes. 6. The [NAD(+)]/[NADH] ratios of cytoplasm and mitochondria are thus greatly different and do not necessarily move in parallel when the metabolic state of the liver changes. 7. The ratios found for the free dinucleotides differ greatly from those recorded for the total dinucleotides because much more NADH than NAD(+) is protein-bound. 8. The bearing of these findings on various problems, including the following, is discussed: the number of NAD(+)-NADH pools in liver cells; the applicability of the method to tissues other than liver; the transhydrogenase activity of glutamate dehydrogenase; the physiological significance of the difference of the redox states of mitochondria and cytoplasm; aspects of the regulation of the redox state of cell compartments; the steady-state concentration of mitochondrial oxaloacetate; the relations between the redox state of cell compartments and ketosis.
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              Family-wide analysis of poly(ADP-ribose) polymerase activity.

              Sejal Vyas, Ivan Matic, Lilen Uchima … (2014)
              The poly(adenosine diphosphate (ADP)-ribose) polymerase (PARP) protein family generates ADP-ribose (ADPr) modifications onto target proteins using NAD(+) as substrate. Based on the composition of three NAD(+) coordinating amino acids, the H-Y-E motif, each PARP is predicted to generate either poly(ADPr) (PAR) or mono(ADPr) (MAR). However, the reaction product of each PARP has not been clearly defined, and is an important priority since PAR and MAR function via distinct mechanisms. Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. We identify automodification sites on seven PARPs, and demonstrate that MAR and PAR generating PARPs modify similar amino acids, suggesting that the sequence and structural constraints limiting PARPs to MAR synthesis do not limit their ability to modify canonical amino-acid targets. In addition, we identify cysteine as a novel amino-acid target for ADP-ribosylation on PARPs.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Reprod Dev
                Journal ID (iso-abbrev): J Reprod Dev
                Journal ID (publisher-id): JRD
                Title: The Journal of Reproduction and Development
                Publisher: The Society for Reproduction and Development
                ISSN (Print): 0916-8818
                ISSN (Electronic): 1348-4400
                Publication date (Electronic): 27 September 2022
                Publication date (Print): December 2022
                Volume: 68
                Issue: 6
                Pages: 345-354
                Affiliations
                [1) ]Sydney School of Veterinary Science, Faculty of Science, The University of Sydney, NSW, 2570, Australia
                [2) ]Priority Research Centre for Reproductive Science, University of Newcastle, Callaghan, NSW, 2308, Australia
                Author notes
                Correspondence: C-L Pollard (e-mail: charley.pollard@ 123456sydney.edu.au )
                Article
                Publisher ID: 2022-052
                DOI: 10.1262/jrd.2022-052
                PMC ID: 9792654
                PubMed ID: 36171094
                SO-VID: e361e583-6fbb-4c4b-9eb0-b7918294d3e2
                Copyright © ©2022 Society for Reproduction and Development
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/)

                History
                Date received : 14 April 2022
                Date accepted : 29 April 2022
                Categories
                Subject: Review

                Keywords: fertility,nicotinamide adenine dinucleotide (nad+),oocyte quality,poly-adp-ribose polymerases (parps),sirtuins
                Data availability:
                Keywords: fertility, nicotinamide adenine dinucleotide (nad+), oocyte quality, poly-adp-ribose polymerases (parps), sirtuins

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