scholarly journals Metabolism and biochemical properties of nicotinamide adenine dinucleotide (NAD) analogs, nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD)

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Keisuke Yaku ◽  
Keisuke Okabe ◽  
Maryam Gulshan ◽  
Kiyoshi Takatsu ◽  
Hiroshi Okamoto ◽  
...  
Keyword(s):  
Stress Responses ◽  
Nicotinamide Adenine Dinucleotide ◽  
Biochemical Properties ◽  
Nicotinamide Adenine ◽  
Repair Gene ◽  
Nad Metabolism ◽  
Nad Glycohydrolase ◽  
Dna Repair Gene

Abstract Nicotinamide adenine dinucleotide (NAD) is an important coenzyme that regulates various metabolic pathways, including glycolysis, β-oxidation, and oxidative phosphorylation. Additionally, NAD serves as a substrate for poly(ADP-ribose) polymerase (PARP), sirtuin, and NAD glycohydrolase, and it regulates DNA repair, gene expression, energy metabolism, and stress responses. Many studies have demonstrated that NAD metabolism is deeply involved in aging and aging-related diseases. Previously, we demonstrated that nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD), which are analogs of NAD, are significantly increased in Nmnat3-overexpressing mice. However, there is insufficient knowledge about NGD and NHD in vivo. In the present study, we aimed to investigate the metabolism and biochemical properties of these NAD analogs. We demonstrated that endogenous NGD and NHD were found in various murine tissues, and their synthesis and degradation partially rely on Nmnat3 and CD38. We have also shown that NGD and NHD serve as coenzymes for alcohol dehydrogenase (ADH) in vitro, although their affinity is much lower than that of NAD. On the other hand, NGD and NHD cannot be used as substrates for SIRT1, SIRT3, and PARP1. These results reveal the basic metabolism of NGD and NHD and also highlight their biological function as coenzymes.

scholarly journals RPH1 and GIS1 Are Damage-Responsive Repressors of PHR1

1999 ◽  
Vol 19 (11) ◽  
pp. 7630-7638 ◽  
Author(s):  
Yeun Kyu Jang ◽  
Ling Wang ◽  
Gwendolyn B. Sancar
Keyword(s):  
Dna Binding ◽  
Binding Site ◽  
Protein S ◽  
Repair Gene ◽  
Repair Capacity ◽  
Pyrimidine Dimers ◽  
Dna Repair Gene ◽  
Damage Response

ABSTRACT The Saccharomyces cerevisiae DNA repair genePHR1 encodes a photolyase that catalyzes the light-dependent repair of pyrimidine dimers. PHR1expression is induced at the level of transcription by a variety of DNA-damaging agents. The primary regulator of the PHR1damage response is a 39-bp sequence called URS PHR1 which is the binding site for a protein(s) that constitutes the damage-responsive repressor PRP. In this communication, we report the identification of two proteins, Rph1p and Gis1p, that regulate PHR1 expression through URS PHR1 . Both proteins contain two putative zinc fingers that are identical throughout the DNA binding region, and deletion of both RPH1 and GIS1 is required to fully derepress PHR1 in the absence of damage. Derepression of PHR1 increases the rate and extent of photoreactivation in vivo, demonstrating that the damage response of PHR1enhances cellular repair capacity. In vitro footprinting and binding competition studies indicate that the sequence AG4(C4T) within URS PHR1 is the binding site for Rph1p and Gis1p and suggests that at least one additional DNA binding component is present in the PRP complex.

Mice Deficient for the Ecto-Nicotinamide Adenine Dinucleotide Glycohydrolase CD38 Exhibit Altered Humoral Immune Responses

Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1324-1333 ◽  
Author(s):  
Debra A. Cockayne ◽  
Tony Muchamuel ◽  
J. Christopher Grimaldi ◽  
Hélène Muller-Steffner ◽  
Troy D. Randall ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Nicotinamide Adenine Dinucleotide ◽  
Antibody Responses ◽  
Nicotinamide Adenine ◽  
Humoral Immune ◽  
Nad Glycohydrolase ◽  
Humoral Immune Responses

Abstract CD38 is a membrane-associated ecto-nicotinamide adenine dinucleotide (NAD+) glycohydrolase that is expressed on multiple hematopoietic cells. The extracellular domain of CD38 can mediate the catalysis of NAD+ to cyclic adenosine diphosphoribose (cADPR), a Ca2+-mobilizing second messenger, adenosine diphosphoribose (ADPR), and nicotinamide. In addition to its enzymatic properties, murine CD38 has been shown to act as a B-cell coreceptor capable of modulating signals through the B-cell antigen receptor. To investigate the in vivo physiological function(s) of this novel class of ectoenzyme we generated mice carrying a null mutation in the CD38 gene. CD38−/− mice showed a complete loss of tissue-associated NAD+ glycohydrolase activity, showing that the classical NAD+ glycohydrolases and CD38 are likely identical. Although murine CD38 is expressed on hematopoietic stem cells as well as on committed progenitors, we show that CD38 is not required for hematopoiesis or lymphopoiesis. However, CD38−/− mice did exhibit marked deficiencies in antibody responses to T-cell–dependent protein antigens and augmented antibody responses to at least one T-cell–independent type 2 polysaccharide antigen. These data suggest that CD38 may play an important role in vivo in regulating humoral immune responses. © 1998 by The American Society of Hematology.

scholarly journals Extracellular Nicotinamide Adenine Dinucleotide Induces T Cell Apoptosis In Vivo and In Vitro

2001 ◽  
Vol 167 (9) ◽  
pp. 4942-4947 ◽  
Author(s):  
Zhang-Xu Liu ◽  
Olga Azhipa ◽  
Shigefumi Okamoto ◽  
Sugantha Govindarajan ◽  
Gunther Dennert
Keyword(s):  
T Cell ◽  
Nicotinamide Adenine Dinucleotide ◽  
Cell Apoptosis ◽  
Nicotinamide Adenine ◽  
T Cell Apoptosis

Mice Deficient for the Ecto-Nicotinamide Adenine Dinucleotide Glycohydrolase CD38 Exhibit Altered Humoral Immune Responses

Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1324-1333 ◽  
Author(s):  
Debra A. Cockayne ◽  
Tony Muchamuel ◽  
J. Christopher Grimaldi ◽  
Hélène Muller-Steffner ◽  
Troy D. Randall ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Nicotinamide Adenine Dinucleotide ◽  
Antibody Responses ◽  
Nicotinamide Adenine ◽  
Humoral Immune ◽  
Nad Glycohydrolase ◽  
Humoral Immune Responses

CD38 is a membrane-associated ecto-nicotinamide adenine dinucleotide (NAD+) glycohydrolase that is expressed on multiple hematopoietic cells. The extracellular domain of CD38 can mediate the catalysis of NAD+ to cyclic adenosine diphosphoribose (cADPR), a Ca2+-mobilizing second messenger, adenosine diphosphoribose (ADPR), and nicotinamide. In addition to its enzymatic properties, murine CD38 has been shown to act as a B-cell coreceptor capable of modulating signals through the B-cell antigen receptor. To investigate the in vivo physiological function(s) of this novel class of ectoenzyme we generated mice carrying a null mutation in the CD38 gene. CD38−/− mice showed a complete loss of tissue-associated NAD+ glycohydrolase activity, showing that the classical NAD+ glycohydrolases and CD38 are likely identical. Although murine CD38 is expressed on hematopoietic stem cells as well as on committed progenitors, we show that CD38 is not required for hematopoiesis or lymphopoiesis. However, CD38−/− mice did exhibit marked deficiencies in antibody responses to T-cell–dependent protein antigens and augmented antibody responses to at least one T-cell–independent type 2 polysaccharide antigen. These data suggest that CD38 may play an important role in vivo in regulating humoral immune responses. © 1998 by The American Society of Hematology.

The Role of NAD+ in Rejuvenating Human Body

2020 ◽  
Vol 2 (12) ◽  
pp. 5-20
Author(s):  
Shyamasri Biswas ◽  
Keyword(s):  
Stress Responses ◽  
Accelerated Aging ◽  
Research Direction ◽  
Future Research ◽  
Repair Gene ◽  
Nad Metabolism ◽  
Secondary Messenger ◽  
Age Related ◽  
Dna Repair Gene ◽  
Nad Depletion

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme and considered an essential cofactor in cellular bioenergetics and adaptive stress responses. It is present in all living cells and governs fundamental biological processes including energy production, DNA repair, gene expression, calcium-dependent secondary messenger signaling and also in immune-regulatory roles. NAD+ depletion has been a subject of intense research due to the reason that it is associated with hallmarks of aging and age-related diseases, such as metabolic disorders, cancer and neurodegenerative diseases. Recent studies have suggested that physiological and pharmacological interventions that elevate cellular NAD+ levels may slow or even reverse the aspects of aging and also delay the progression of age-related diseases. In this min-review, we have described the roles of NAD+ in relationships to aging and major age-related diseases. The emphasis is on the contribution of NAD+ depletion to aging along with strategies to modulate NAD+ metabolism through physiological and pharmacological pathways. Recent human clinical studies on NAD+ boosting are summarized. We have specifically addressed how boosting NAD+ levels could potentially play an important role as a promising therapeutic strategy to counter aging-associated pathologies and accelerated aging. Finally, a brief perspective on the future research direction is presented.

scholarly journals SEQUENCE AND TRANSCRIPTS OF THE BACTERIOPHAGE T4 DNA REPAIR GENE uvsY

Genetics ◽  
1986 ◽  
Vol 114 (4) ◽  
pp. 1061-1079
Author(s):  
Michael E Gruidl ◽  
Gisela Mosig
Keyword(s):  
Bacteriophage T4 ◽  
Open Reading Frames ◽  
Repair Gene ◽  
Protein Marker ◽  
Reading Frame ◽  
Phage T4 ◽  
Dna Repair Gene ◽  
A Minor

ABSTRACT We have cloned, sequenced and analyzed transcription of the phage T4 uvsY gene. This gene is transcribed from a single gp MotA-dependent middle promoter to give a major transcript of approximately 930 nucleotides and a minor transcript of approximately 620 nucleotides. All in vivo and in vitro uvsY transcripts show anomalous migration in agarose gels. The uvsY transcript contains an open reading frame coding for an 137 amino acid [15.8 kilodaltons (kD)] UvsY protein and two unidentified open reading frames, ORF UvsY.-1 (9.0 kD) and ORF UvsY.-2 (6.0 kD). Our DNA sequence differs in only three places from that published by Takahashi et al.However, one of these changes alters the predicted carboxy terminus of the UvsY protein. Marker rescue experiments map gene 25 to the region upstream of uvsY. Gene 25 is likely, although not certain, to correspond to an ORF that is found upstream from uvsY and is translated in the same direction.

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