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Nicotinamide‐adenine dinucleotide (NAD) is involved in redox homeostasis and acts as a substrate for NADases, including poly(ADP‐ribose) polymerases (PARPs) that add poly(ADP‐ribose) polymers to proteins and DNA, and sirtuins that deacetylate proteins. Nicotinamide, a by‐product of NADases increases circadian period in both plants and animals. In mammals, the effect of nicotinamide on circadian period might be mediated by the PARPs and sirtuins because they directly bind to core circadian oscillator genes. We have investigated whether PARPs and sirtuins contribute to the regulation of the circadian oscillator in Arabidopsis. We found no evidence that PARPs and sirtuins regulate the circadian oscillator of Arabidopsis or are involved in the response to nicotinamide. RNA‐seq analysis indicated that PARPs regulate the expression of only a few genes, including FLOWERING LOCUS C. However, we found profound effects of reduced sirtuin 1 expression on gene expression during the day but not at night, and an embryo lethal phenotype in knockouts. Our results demonstrate that PARPs and sirtuins are not associated with NAD regulation of the circadian oscillator and that sirtuin 1 is associated with daytime regulation of gene expression. Nicotinamide can lengthen circadian period in mammals. We find that in Arabidopsis PARPs and sirtuins are not associated with nicotiniamide regulation of the circadian oscillator but sirtuin 1 is associated with daytime regulation of gene expression. This demonstrates a major difference in the regulation of the circadian oscillator by nicotinamide in plants and animals and identifies a major role for sirtuin 1 in affecting gene expression. [ABSTRACT FROM AUTHOR]

Narrow band (311 nm) UVB phototherapy is established treatment for psoriasis. DNA is a target for UVB via formation of cyclobutane pyrimidine dimers, which trigger loss of dendritic cells and macrophages, and inhibit CD4+ and CD8+ T cells. UV causes the formation of thymine dimers, which activate nuclear enzyme poly(ADP-ribose) polymerase. The fact that poly(ADP-ribose) polymerase utilizes nicotinamide-adenine dinucleotide (NAD) explains NAD decreases after UV irradiation. NADH regulates transcriptional repressor carboxyl-terminal binding protein, whereas NAD(+) is a co-substrate in deacylation reactions, engaged in genomic silencing. Hyperproliferation of psoriatic keratinocytes requires NADH during oxidative phosphorylation. In one study the NADH fluorescence (reflecting NADH amount) was reduced in psoriatic lesions. NAD(+) used topically was as effective as 0.1% anthralin. Spectrophotometry enables real-time measurements of NADH fluorescence in vivo in the epidermis and points out a new direction for application of biophysics in medicine.

Methotrexate inhibits tetrahydrofolic acid production and influences mitochondrial oxygen uptake and activity of several enzymes in the respiratory chain reactions, which utilize nicotinamide adenine dinucleotide-linked (NAD-linked) substrates. Hyperproliferation of keratinocytes in psoriasis requires oxidative phosphorylation, in which the reduced form of nicotinamide adenine dinucleotide (NADH) is an electron donor. One hypothesis links increased cellular metabolism to the increased NADH/NAD+ ratio; as expected, the topical application of NAD+ (oxidized form of nicotinamide-adenine dinucleotide) resulted in a clinical improvement of psoriatic lesions in one study. Nevertheless, another report revealed reduced fluorescence of NADH in psoriatic plaques. The biological activity of NADH is not limited only to serving as the electron donor. It was also found to regulate gene transcription. [ABSTRACT FROM AUTHOR]

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Nicotinamide adenine dinucleotide (NAD) serves as an essential redox co-factor and mediator of multiple biological processes. Besides its well-established role in electron transfer reactions, NAD serves as a substrate for other biotransformations, which, at the molecular level, can be classified as protein post-translational modifications (protein deacylation, mono-, and polyADP-ribosylation) and formation of signaling molecules (e.g., cyclic ADP ribose). These biochemical reactions control many crucial biological processes, such as cellular signaling and recognition, DNA repair and epigenetic modifications, stress response, immune response, aging and senescence, and many others. However, the links between the biological effects and underlying molecular processes are often poorly understood. Moreover, NAD has recently been found to tag the 5′-ends of some cellular RNAs, but the function of these NAD-capped RNAs remains largely unrevealed. Synthetic NAD analogs are invaluable molecular tools to detect, monitor, structurally investigate, and modulate activity of NAD-related enzymes and biological processes in order to aid their deeper understanding. Here, we review the recent advances in the design and development of NAD analogs as probes for various cellular NAD-related enzymes, enzymatic inhibitors with anticancer or antimicrobial therapeutic potential, and other NAD-related chemical biology tools. We focus on research papers published within the last 10 years.

A review of optical, chemical, and biological sensors to detect metabolic activity at the single-cell level is presented in the context of the development of lab-on-a-chip research instrumentation. The sensors reviewed include optical sensors, at both research and commercial levels, that can optically detect intracellular metabolites including adenosine triphosphate, nicotinamide-adenine dinucleotide, reduced flavin adenine dinucleotide, and other metabolites, including oxygen, carbon dioxide, and glucose. Methods to optically detect pH changes which are a general indicator of activity in extracellular space are also briefly reviewed. Performance metrics such as sensitivity, sensor size, drift, time response, and sensing range are included when available. Highly suitable optical sensor technologies for monitoring cellular metabolic activity include luminescent (fluorescent, phosphorescent, and chemiluminescent) and colorimetric optical probes. Different approaches to extracting luminescent and colorimetric information are reviewed, including benchtop techniques, fiber-optic approaches, and the use of probes encapsulated by biologically localized embedding. A brief discussion of alternate optical sensor technologies, such as surface plasmon resonance and infrared absorption spectroscopy, is also presented. [ABSTRACT FROM PUBLISHER]

This pilot study was part of a larger study aimed at characterizing the pharmacokinetic profile of intravenous nicotinamide adenine dinucleotide (NAD+) and measured cognitive performance following IV NAD+ in healthy male subjects. We hypothesized that IV NAD+ would improve cognitive performance scores as compared to baseline performance. Randomized, controlled study. Private mental health treatment center located in Springfield, LA. Fifteen healthy male participants (4 Saline/11 IV NAD+) between the ages of 30-55 met inclusion criteria. Participants received 5 consecutive days of IV NAD+ (750 mg/day) or saline infusions Researchers used the MicroCog™ Assessment of Cognitive Function to measure cognitive abilities on three levels: (Level 1) Attention, reaction time, memory, reasoning and spatial processing; (Level 2) Information processing speed and accuracy; and (Level 3) Global cognitive functioning and global cognitive proficiency. Participants completed baseline assessment (DAY 0) and repeated the task after the end of the IV infusion protocol (DAY 6). No differences between SAL and NAD+ groups were noted on DAY 0 in any of the 8 subtests evaluated. However, groups showed differences in the magnitude of improvement over days compared to their respective baselines. The NAD+ group reached significance on 6/8 tests, while the SAL group showed significant improvement on 2/8 tests. The findings when compared to respective baseline performance scores indicated a greater magnitude of change over and above "practice effects". These results combined with case reports in Parkinson's disease patients suggest that implementation of a standardized cognitive assessment is a practical and effective way to establish efficacy of IV NAD+ treatment for clinical conditions involving cognitive impairment Dr. R. Mestayer is a director of NAD+ Research Inc., and medical director of the Springfield Wellness Center that uses IV NAD+ as a clinical therapy. Dr. Broom-Gibson received consulting fees from NAD+ Research Inc. [ABSTRACT FROM AUTHOR]

Nicotinamide adenine dinucleotide (NAD) serves as an essential redox co-factor and mediator of multiple biological processes. Besides its well-established role in electron transfer reactions, NAD serves as a substrate for other biotransformations, which, at the molecular level, can be classified as protein post-translational modifications (protein deacylation, mono-, and polyADP-ribosylation) and formation of signaling molecules (e.g., cyclic ADP ribose). These biochemical reactions control many crucial biological processes, such as cellular signaling and recognition, DNA repair and epigenetic modifications, stress response, immune response, aging and senescence, and many others. However, the links between the biological effects and underlying molecular processes are often poorly understood. Moreover, NAD has recently been found to tag the 5′-ends of some cellular RNAs, but the function of these NAD-capped RNAs remains largely unrevealed. Synthetic NAD analogs are invaluable molecular tools to detect, monitor, structurally investigate, and modulate activity of NAD-related enzymes and biological processes in order to aid their deeper understanding. Here, we review the recent advances in the design and development of NAD analogs as probes for various cellular NAD-related enzymes, enzymatic inhibitors with anticancer or antimicrobial therapeutic potential, and other NAD-related chemical biology tools. We focus on research papers published within the last 10 years. [ABSTRACT FROM AUTHOR]

The complete mitochondrial genome of the African Penguin (Spheniscus demersus) was sequenced. The molecule was sequenced via next generation sequencing and primer walking. The size of the genome is 17,346 bp in length. Comparison with the mitochondrial DNA of two other penguin genomes that have so far been reported was conducted namely; Little blue penguin (Eudyptula minor) and the Rockhopper penguin (Eudyptes chrysocome). This analysis made it possible to identify common penguin mitochondrial DNA characteristics. The S. demersus mtDNA genome is very similar, both in composition and length to both the E. chrysocome and E. minor genomes. The gene content of the African penguin mitochondrial genome is typical of vertebrates and all three penguin species have the standard gene order originally identified in the chicken. The control region for S. demersus is located between tRNA-Glu and tRNA-Phe and all three species of penguins contain two sets of similar repeats with varying copy numbers towards the 3' end of the control region, accounting for the size variance. This is the first report of the complete nucleotide sequence for the mitochondrial genome of the African penguin, S. demersus. These results can be subsequently used to provide information for penguin phylogenetic studies and insights into the evolution of genomes., (© 2013 Elsevier B.V. All rights reserved.)

This study evaluated the protective effects of Aplysin against ethanol-induced hepatic injury in rats and analyzed the associated mechanisms. Rats were administered orally with ethanol 8-12 ml/kg bw excluding the rats in the control group at 1h after rats were administered by gavage doses of Aplysin (50, 100, and 150 mg/kg bw) every day. After 6 weeks, rats were sacrificed, and liver injury was evaluated by biochemical and pathological examination. Hepatocyte apoptosis was analyzed by annexin V-FITC/PI staining. Ethanol metabolic enzymes, oxidative stress, mitochondrial function, and Bcl-2, Bax, cytochrome c and cleaved caspase-3 expressions were evaluated by western blot analysis. These results demonstrated that Aplysin exhibited a significant hepatoprotective effect. In the ethanol-treated group, cytochrome P4502E1 and alcohol dehydrogenase were increased significantly in liver tissue. Moreover, Aplysin not only significantly reversed the ratio of NAD(+)/NADH and mitochondrial glutathione depletion, but also reversed the decreased activity of mitochondrial respiratory chain complexes I, III and IV. Overexpression of cytoplasmic cytochrome c and caspase-3 activation was suppressed by Aplysin. These results suggest that Aplysin alleviates hepatocyte apoptosis by modulating the ethanol-metabolizing pathway, attenuating oxidative stress, ameliorating mitochondrial function, inhibiting mitochondrial damage-mediated apoptosis, which ultimately prevent and repair alcoholic liver injury., (Copyright © 2013 Elsevier Ltd. All rights reserved.)