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Nicotinamide adenine dinucleotide

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https://www.readbyqxmd.com/read/29656576/repurposing-carbamazepine-for-the-treatment-of-amyotrophic-lateral-sclerosis-in-sod1-g93a-mouse-model
#1
Jing-Jing Zhang, Qin-Ming Zhou, Sheng Chen, Wei-Dong Le
AIMS: To investigate the effect and mechanisms of carbamazepine (CBZ) on the onset and progression of amyotrophic lateral sclerosis (ALS) in SOD1-G93A mouse model. METHODS: Starting from 64 days of age, SOD1-G93A mice were orally administered with CBZ at 200 mg/kg once daily until death. The disease onset and life span of SOD1-G93A mice were recorded. Motor neurons (MNs) in anterior horn of spinal cord were quantified by Nissl staining and SMI-32 immunostaining...
April 14, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29655790/hdac11-deletion-reduces-fructose-induced-cardiac-dyslipidemia-apoptosis-and-inflammation-by-attenuating-oxidative-stress-injury
#2
Xiao-Di Fan, Lan-Lan Wan, Man Duan, Shan Lu
Diabetes mellitus (DM) is a risk factor for abnormal heart development, but the molecular mechanism remains obscure. Histone deacetylase 11 (HDAC11), the most recently identified histone deacetylase, is the sole member of class IV HDACs. However, its role in diabetic cardiac injury is still poorly understood. In the present study, we attempted to explore the effects of HDAC11 on fructose (Fru)-induced cardiac injury using the wild type (HDAC11+/+ ) and knockout (HDAC11-/- ) mice. The results indicated that HDAC11 was significantly expressed in human and mouse diabetic heart failure (DHF) hearts...
April 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29651790/novel-insights-for-inhibiting-mutant-heterodimer-idh1-wt-r132h-in-cancer-an-in-silico-approach
#3
Ezequiel Iván Juritz, Juan Pablo Bascur, Daniel Eduardo Almonacid, Fernando Danilo González-Nilo
BACKGROUND: Isocitrate dehydrogenase 1 (IDH1) is a dimeric enzyme responsible for supplying the cell's nicotinamide adenine dinucleotide phosphate (NADPH) reserves via dehydrogenation of isocitrate (ICT) and reduction of NADP+. Mutations in position R132 trigger cancer by enabling IDH1 to produce D-2-hydroxyglutarate (2-HG) and reduce inhibition by ICT. Mutant IDH1 can be found as a homodimer or a heterodimer. OBJECTIVE: We propose a novel strategy to inhibit IDH1 R132 variants as a means not to decrease the concentration of 2-HG but to provoke a cytotoxic effect, as the cell malignancy at this point no longer depends on 2-HG...
April 12, 2018: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/29644063/metabolic-adaptability-in-hexavalent-chromium-treated-renal-tissue-an-in-vivo-study
#4
Kanu Shil, Sudipta Pal
Background: Hexavalent chromium [Cr(VI)], an environmental pollutant that originates mostly from anthropogenic sources, is a serious threat to human health. After entering into cells, Cr(VI) is capable of producing excessive free radicals and causing tissue damage. The present study aims to reveal the toxic manifestation of Cr(VI) on the metabolic activity of renal tissue. Methods: Male Swiss albino mice were treated orally with potassium dichromate (K2 Cr2 O7 ) at a dose of 10 mg/kg body weight for a period of 30 days...
April 2018: Clinical Kidney Journal
https://www.readbyqxmd.com/read/29643724/resolvin-d1-promotes-corneal-epithelial-wound-healing-and-restoration-of-mechanical-sensation-in-diabetic-mice
#5
Zhenzhen Zhang, Xiaoli Hu, Xia Qi, Guohu Di, Yangyang Zhang, Qian Wang, Qingjun Zhou
Purpose: To investigate the effect and mechanism of proresolving lipid mediator resolvin D1 (RvD1) on the corneal epithelium and the restoration of mechanical sensation in diabetic mice. Methods: Type 1 diabetes was induced in mice with intraperitoneal streptozocin injections. The healthy and diabetic mice underwent removal of the central corneal epithelium, and then 100 ng/ml RvD1 or its formyl peptide receptor 2 (FPR2) antagonist WRW4 was used to treat the diabetic mice...
2018: Molecular Vision
https://www.readbyqxmd.com/read/29642910/localization-and-phosphorylation-of-plasmodium-falciparum-nicotinamide-nicotinate-mononucleotide-adenylyltransferase-pfnmnat-in-intraerythrocytic-stages
#6
Carlos A Nieto, Lina M Sánchez, Diana M Sánchez, Gonzalo J Díaz, María H Ramírez
BACKGROUND: Nicotinamide adenine dinucleotide (NAD+) is an essential molecule in the energy metabolism of living beings, and it has various cellular functions. The main enzyme in the biosynthesis of this nucleotide is nicotinamide/nicotinate mononucleotide adenylyltransferase (NMNAT, EC 2.7.7.1/18) because it is the convergence point for all known biosynthetic pathways. NMNATs have divergences in both the number of isoforms detected and their distribution, depending on the organism. METHODS: In the laboratory of basic research in biochemistry (LIBBIQ: acronym in Spanish) the NMNATs of protozoan parasites (Leishmania braziliensis, Plasmodium falciparum, Trypanosoma cruzi, and Giardia duodenalis) have been studied, analysing their catalytic properties through the use of proteins...
April 11, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29642561/%C3%AE-nicotinamide-adenine-dinucleotide-%C3%AE-nad-inhibits-atp-dependent-il-1%C3%AE-release-from-human-monocytic-cells
#7
Sebastian Daniel Hiller, Sarah Heldmann, Katrin Richter, Innokentij Jurastow, Mira Küllmar, Andreas Hecker, Sigrid Wilker, Gabriele Fuchs-Moll, Ivan Manzini, Günther Schmalzing, Wolfgang Kummer, Winfried Padberg, J Michael McIntosh, Jelena Damm, Anna Zakrzewicz, Veronika Grau
While interleukin-1β (IL-1β) is a potent pro-inflammatory cytokine essential for host defense, high systemic levels cause life-threatening inflammatory syndromes. ATP, a stimulus of IL-1β maturation, is released from damaged cells along with β-nicotinamide adenine dinucleotide (β-NAD). Here, we tested the hypothesis that β-NAD controls ATP-signaling and, hence, IL-1β release. Lipopolysaccharide-primed monocytic U937 cells and primary human mononuclear leukocytes were stimulated with 2'(3')- O -(4-benzoyl-benzoyl)ATP trieethylammonium salt (BzATP), a P2X7 receptor agonist, in the presence or absence of β-NAD...
April 10, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29629557/structural-basis-for-recognition-of-l-lysine-l-ornithine-and-l-2-4-diamino-butyric-acid-by-lysine-cyclodeaminase
#8
Kyungjin Min, Hye-Jin Yoon, Atsushi Matsuura, Yong Hwan Kim, Hyung Ho Lee
L-pipecolic acid is a non-protein amino acid commonly found in plants, animals, and microorganisms. It is a well-known precursor to numerous microbial secondary metabolites and pharmaceuticals, including anticancer agents, immunosuppressants, and several antibiotics. Lysine cyclodeaminase (LCD) catalyzes β-deamination of L-lysine into L-pipecolic acid using β-nicotinamide adenine dinucleotide as a cofactor. Expression of a human homolog of LCD, μ-crystallin, is elevated in prostate cancer patients. To understand the structural features and catalytic mechanisms of LCD, we determined the crystal structures of Streptomyces pristinaespiralis LCD (SpLCD) in (i) a binary complex with NAD+, (ii) a ternary complex with NAD+ and L-pipecolic acid, (iii) a ternary complex with NAD+ and L-proline, and (iv) a ternary complex with NAD+ and L-2,4-diamino butyric acid...
April 5, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29626150/rac1-modulates-endothelial-function-and-platelet-aggregation-in-diabetes-mellitus
#9
Gabriele Giacomo Schiattarella, Albino Carrizzo, Federica Ilardi, Antonio Damato, Mariateresa Ambrosio, Michele Madonna, Valentina Trimarco, Marina Marino, Elena De Angelis, Silvio Settembrini, Cinzia Perrino, Bruno Trimarco, Giovanni Esposito, Carmine Vecchione
BACKGROUND: Vascular complications and abnormal platelet function contribute to morbidity and mortality in diabetes mellitus. We hypothesized that the Rho-related GTPase protein, Rac1, can influence both endothelial and platelet function and might represent a potential novel therapeutic target in diabetes mellitus. METHODS AND RESULTS: We used both in vitro and ex vivo approaches to test the effects of pharmacological inhibition of Rac1 during hyperglycemic condition...
April 6, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29623912/cerebral-ischemia-and-neuroregeneration
#10
REVIEW
Reggie H C Lee, Michelle H H Lee, Celeste Y C Wu, Alexandre Couto E Silva, Harlee E Possoit, Tsung-Han Hsieh, Alireza Minagar, Hung Wen Lin
Cerebral ischemia is one of the leading causes of morbidity and mortality worldwide. Although stroke (a form of cerebral ischemia)-related costs are expected to reach 240.67 billion dollars by 2030, options for treatment against cerebral ischemia/stroke are limited. All therapies except anti-thrombolytics (i.e., tissue plasminogen activator) and hypothermia have failed to reduce neuronal injury, neurological deficits, and mortality rates following cerebral ischemia, which suggests that development of novel therapies against stroke/cerebral ischemia are urgently needed...
March 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29619018/-s-adenosyl-l-homocysteine-hydrolase-inhibition-by-a-synthetic-nicotinamide-cofactor-biomimetic
#11
Lyn L Kailing, Daniela Bertinetti, Caroline E Paul, Tomasz Manszewski, Mariusz Jaskolski, Friedrich W Herberg, Ioannis V Pavlidis
S -adenosyl-L-homocysteine (SAH) hydrolases (SAHases) are involved in the regulation of methylation reactions in many organisms and are thus crucial for numerous cellular functions. Consequently, their dysregulation is associated with severe health problems. The SAHase-catalyzed reaction is reversible and both directions depend on the redox activity of nicotinamide adenine dinucleotide (NAD+ ) as a cofactor. Therefore, nicotinamide cofactor biomimetics (NCB) are a promising tool to modulate SAHase activity...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29614635/oxidative-stress-in-sickle-cell-disease-more-than-a-damp-squib
#12
Eduard J van Beers, Richard van Wijk
Sickle cell disease (SCD) is a monogenetic disorder marked by hemolytic anemia and vaso-occlusive complications. The hallmark of SCD is the intracellular polymerization of sickle hemoglobin (HbS) after deoxygenation, and the subsequent characteristic shape change (sickling) of red cells. Vaso-occlusion occurs after endothelial activation, expression of adhesion molecules and subsequent adhesion of leucocytes and sickle erythrocytes to the vascular wall. Here we review how oxidative stress from various sources influences this process...
2018: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/29609419/add-on-therapy-with-the-%C3%AE-blockers-tamsulosin-and-naftopidil-improves-voiding-function-by-enhancing-neuronal-activity-in-prostatic-hyperplasia-rats
#13
Il-Gyu Ko, Lakkyong Hwang, Jun-Jang Jin, Sang-Hoon Kim, Jin Hee Han, Jung Won Jeon, Sung Tae Cho
PURPOSE: Benign prostatic hyperplasia (BPH) impacts quality of life in men by causing lower urinary tract symptoms. α1-Adrenoceptor (α1-AR) blockers improve lower urinary tract symptoms. We investigated the efficacy of add-on therapy with α1-AR blockers on BPH rats. METHODS: Rats in the drug-treated groups were orally administered each drug once a day for 30 days after orchiectomy. To induce BPH, rats were castrated and testosterone (20 mg/kg) was injected subcutaneously once per day for 30 days...
March 2018: International Neurourology Journal
https://www.readbyqxmd.com/read/29609022/nadph-dependent-and-independent-disulfide-reductase-systems
#14
REVIEW
Colin G Miller, Arne Holmgren, Elias S J Arnér, Edward E Schmidt
Over the past seven decades, research on autotrophic and heterotrophic model organisms has defined how the flow of electrons ("reducing power") from high-energy inorganic sources, through biological systems, to low-energy inorganic products like water, powers all of Life's processes. Universally, an initial major biological recipient of these electrons is nicotinamide adenine dinucleotide-phosphate, which thereby transits from an oxidized state (NADP+ ) to a reduced state (NADPH). A portion of this reducing power is then distributed via the cellular NADPH-dependent disulfide reductase systems as sequential reductions of disulfide bonds...
March 30, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29607689/curcumin-and-resveratrol-rescue-cortical-hippocampal-system-from-chronic-fluoride-induced-neurodegeneration-and-enhance-memory-retrieval
#15
Chhavi Sharma, Pooja Suhalka, Maheep Bhatnagar
OBJECTIVE: The aim of this study were: (1) To evaluate neuroprotective effect of Resveratrol and Curcumin on NADPH-d (Nicotinamide adenine dinucleotide phosphate diaphorase) activity in neuronal cell in sub regions of mice brain (2) To evaluate the effects on antioxidant status, and (3) To evaluate the protective effects of phytochemicals on learning and memory following fluoride exposure. METHOD: Young Mice (one month old, B.W. 30±5mg) were provided to 120 ppm sodium fluoride dissolved in drinking water...
April 2, 2018: International Journal of Neuroscience
https://www.readbyqxmd.com/read/29604362/lacking-ketohexokinase-a-exacerbates-renal-injury-in-streptozotocin-induced-diabetic-mice
#16
Tomohito Doke, Takuji Ishimoto, Takahiro Hayasaki, Satsuki Ikeda, Masako Hasebe, Akiyoshi Hirayama, Tomoyoshi Soga, Noritoshi Kato, Tomoki Kosugi, Naotake Tsuboi, Miguel A Lanaspa, Richard J Johnson, Kenji Kadomatsu, Shoichi Maruyama
OBJECTIVE: Ketohexokinase (KHK), a primary enzyme in fructose metabolism, has two isoforms, namely, KHK-A and KHK-C. Previously, we reported that renal injury was reduced in streptozotocin-induced diabetic mice which lacked both isoforms. Although both isoforms express in kidney, it has not been elucidated whether each isoform plays distinct roles in the development of diabetic kidney disease (DKD). The aim of the study is to elucidate the role of KHK-A for DKD progression. MATERIALS AND METHODS: Diabetes was induced by five consecutive daily intraperitoneal injections of streptozotocin (50 mg/kg) in C57BL/6 J wild-type mice, mice lacking KHK-A alone (KHK-A KO), and mice lacking both KHK-A and KHK-C (KHK-A/C KO)...
March 28, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29602494/motor-coordination-and-synaptic-plasticity-deficits-are-associated-with-increased-cerebellar-activity-of-nadph-oxidase-camkii-and-pkc-at-preplaque-stage-in-the-tgcrnd8-mouse-model-of-alzheimer-s-disease
#17
Roberto Russo, Fabio Cattaneo, Pellegrino Lippiello, Claudia Cristiano, Fabio Zurlo, Martina Castaldo, Carlo Irace, Tiziana Borsello, Rita Santamaria, Rosario Ammendola, Antonio Calignano, Maria Concetta Miniaci
Numerous studies indicate that the cerebellum undergoes structural and functional neurodegenerative changes in Alzheimer's disease. The purpose of this study was to examine the extent of cerebellar alterations at early, preplaque stage of the pathology in TgCRND8 mice through behavioral, electrophysiological, and molecular analysis. Balance beam test and foot-printing analysis revealed significant motor coordination and balance deficits in 2-month-old TgCRND8 mice compared to their littermates. Patch-clamp recordings performed on cerebellar slices of transgenic mice showed synaptic plasticity deficit and loss of noradrenergic modulation at parallel fiber-Purkinje cell synapse suggesting an early dysfunction of the cerebellar circuitry due to amyloid precursor protein overexpression...
March 5, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29599478/chronic-nicotinamide-riboside-supplementation-is-well-tolerated-and-elevates-nad-in-healthy-middle-aged-and-older-adults
#18
Christopher R Martens, Blair A Denman, Melissa R Mazzo, Michael L Armstrong, Nichole Reisdorph, Matthew B McQueen, Michel Chonchol, Douglas R Seals
Nicotinamide adenine dinucleotide (NAD+ ) has emerged as a critical co-substrate for enzymes involved in the beneficial effects of regular calorie restriction on healthspan. As such, the use of NAD+ precursors to augment NAD+ bioavailability has been proposed as a strategy for improving cardiovascular and other physiological functions with aging in humans. Here we provide the evidence in a 2 × 6-week randomized, double-blind, placebo-controlled, crossover clinical trial that chronic supplementation with the NAD+ precursor vitamin, nicotinamide riboside (NR), is well tolerated and effectively stimulates NAD+ metabolism in healthy middle-aged and older adults...
March 29, 2018: Nature Communications
https://www.readbyqxmd.com/read/29596860/endothelial-dysfunction-endothelial-nitric-oxide-bioavailability-tetrahydrobiopterin-and-5-methyltetrahydrofolate-in-cardiovascular-disease-where-are-we-with-therapy
#19
REVIEW
Matthew F Yuyun, Leong L Ng, G André Ng
Homeostasis around vascular endothelium is a function of the equilibrium between the bioavailability of nitric oxide (NO) and oxidizing reactive oxygen species (ROS). Within the vascular endothelium, NO enhances vasodilatation, reduces platelet aggression and adhesion (anti-thrombotic), prevents smooth muscle proliferation, inhibits adhesion of leukocytes and expression of pro-inflammatory cytokines genes (anti-inflammatory), and counters the oxidation of low density lipoprotein (LDL) cholesterol. A shift in the equilibrium that favours NO deficiency and ROS formation leads to endothelial dysfunction and cardiovascular disease...
March 26, 2018: Microvascular Research
https://www.readbyqxmd.com/read/29596303/phasor-based-endogenous-nad-p-h-fluorescence-lifetime-imaging-unravels-specific-enzymatic-activity-of-neutrophil-granulocytes-preceding-netosis
#20
Ruth Leben, Lennard Ostendorf, Sofie van Koppen, Asylkhan Rakhymzhan, Anja E Hauser, Helena Radbruch, Raluca A Niesner
Time-correlated single-photon counting combined with multi-photon laser scanning microscopy has proven to be a versatile tool to perform fluorescence lifetime imaging in biological samples and, thus, shed light on cellular functions, both in vitro and in vivo. Here, by means of phasor-analyzed endogenous NAD(P)H (nicotinamide adenine dinucleotide (phosphate)) fluorescence lifetime imaging, we visualize the shift in the cellular metabolism of healthy human neutrophil granulocytes during phagocytosis of Staphylococcus aureus pHrodo™ beads...
March 29, 2018: International Journal of Molecular Sciences
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