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Nicotinamide

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https://www.readbyqxmd.com/read/28650465/mcu-dependent-mitochondrial-ca-2-inhibits-nad-sirt3-sod2-pathway-to-promote-ros-production-and-metastasis-of-hcc-cells
#1
T Ren, H Zhang, J Wang, J Zhu, M Jin, Y Wu, X Guo, L Ji, Q Huang, H Zhang, H Yang, J Xing
Mitochondrial Ca(2+) signaling, which is strongly dependent on the mitochondrial Ca(2+) uniporter (MCU) complex, has a series of key roles in physiopathological processes, including energy metabolism, reactive oxygen species (ROS) production and cell apoptosis. However, a mechanistic understanding of how the mitochondrial Ca(2+) signaling is remodeled and its functional roles remains greatly limited in cancers, especially in hepatocellular carcinoma. Here we demonstrated that the MCU complex was dysregulated in hepatocellular carcinoma (HCC) cells and significantly correlated with metastasis and poor prognosis of HCC patients...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28649560/escaping-death-mitochondrial-redox-homeostasis-in-cancer-cells
#2
REVIEW
Francesco Ciccarese, Vincenzo Ciminale
Reactive oxygen species (ROS) are important signaling molecules that act through the oxidation of nucleic acids, proteins, and lipids. Several hallmarks of cancer, including uncontrolled proliferation, angiogenesis, and genomic instability, are promoted by the increased ROS levels commonly found in tumor cells. To counteract excessive ROS accumulation, oxidative stress, and death, cancer cells tightly regulate ROS levels by enhancing scavenging enzymes, which are dependent on the reducing cofactor nicotinamide adenine dinucleotide phosphate (NADPH)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28649105/-aging-and-homeostasis-age-associated-diseases-and-clinical-application-of-nmn-nicotinamide-mononucleotide
#3
Junichiro Irie, Hiroshi Itoh
Sirtuins are NAD(+)-dependent deacetylase and have drawn much attention as important regulators of aging and longevity. Because NAD(+) decline during the aging process, the approach to regulating aging using NAD(+) precursor such as nicotinamide mononucleotide (NMN) to replenish cellular NAD(+) through the activation of sirtuins have been investigated. In various animal models, NMN has been shown to mitigate age-associated physiological changes in liver, adipose tissue, muscle, pancreas, kidney, retina, and central nerve system...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28648609/critical-role-of-water-molecules-in-proton-translocation-by-the-membrane-bound-transhydrogenase
#4
Pius S Padayatti, Josephine H Leung, Paween Mahinthichaichan, Emad Tajkhorshid, Andrii Ishchenko, Vadim Cherezov, S Michael Soltis, J Baz Jackson, C David Stout, Robert B Gennis, Qinghai Zhang
The nicotinamide nucleotide transhydrogenase (TH) is an integral membrane enzyme that uses the proton-motive force to drive hydride transfer from NADH to NADP(+) in bacteria and eukaryotes. Here we solved a 2.2-Å crystal structure of the TH transmembrane domain (Thermus thermophilus) at pH 6.5. This structure exhibits conformational changes of helix positions from a previous structure solved at pH 8.5, and reveals internal water molecules interacting with residues implicated in proton translocation. Together with molecular dynamics simulations, we show that transient water flows across a narrow pore and a hydrophobic "dry" region in the middle of the membrane channel, with key residues His42(α2) (chain A) being protonated and Thr214(β) (chain B) displaying a conformational change, respectively, to gate the channel access to both cytoplasmic and periplasmic chambers...
June 13, 2017: Structure
https://www.readbyqxmd.com/read/28647364/crystal-structures-of-the-isochorismatase-domains-from-vibrio-anguillarum
#5
Jiansen Du, Tian Deng, Qingjun Ma
Antibiotic resistance is becoming a global threat and overuse of antibiotics in aquaculture disease control worsens the situation. To reduce the risk of drug resistance developed in aquaculture, safer biocontrol programs are needed. Antivirulence therapy, with less chance for developing drug resistance, is a promising approach. To facilitate antivirulence inhibitor design against Vibrio anguillarum, a serious aquaculture pathogen, we present crystal structures for isochorismatase domains of AngB and VabB, which are required to synthesize siderophore, a critical virulence factor...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28647274/sonic-hedgehog-pathway-suppression-and-reactivation-accelerates-differentiation-of-rat-adipose-derived-mesenchymal-stromal-cells-toward-insulin-producing-cells
#6
Dian Dayer, Mahmoud Hashemi Tabar, Eskandar Moghimipour, Mohammad Reza Tabandeh, Ata A Ghadiri, Elham Allah Bakhshi, Mahmoud Orazizadeh, Mohammad Ali Ghafari
BACKGROUND AIMS: Sonic hedgehog (Shh) is an intercellular signaling molecule that regulates pancreas development in mammals. Manipulation of Shh signaling pathway can be used as reliable approach to improve the generation of functional insulin-producing cells (IPCs) from mesenchymal stromal cells (MSCs). METHODS: In the present study, a novel differentiation protocol was used to produce IPCs from adipose tissue-derived MSCs (ATDMSCs) based on sequential inhibition and reactivation of Shh pathway...
June 21, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28644864/overexpression-and-characterization-of-two-types-of-nitrile-hydratases-from-rhodococcus-rhodochrous-j1
#7
Yao Lan, Xiaohuan Zhang, Zhongmei Liu, Li Zhou, Ruihua Shen, Xianping Zhong, Wenjing Cui, Zhemin Zhou
Nitrile hydratase (NHase) from Rhodococcus rhodochrous J1 is widely used for industrial production of acrylamide and nicotinamide. However, the two types of NHases (L-NHase and H-NHase) from R. rhodochrous J1 were only slightly expressed in E. coli by routine methods, which limits the comprehensive and systematic characterization of the enzyme properties. We successfully expressed the two types of recombinant NHases in E. coli by codon-optimization, engineering of Ribosome Binding Site (RBS) and spacer sequences...
2017: PloS One
https://www.readbyqxmd.com/read/28642875/rapid-elimination-of-blood-alcohol-using-erythrocytes-mathematical-modeling-and-in-vitro-study
#8
Yuliya G Alexandrovich, Elena A Kosenko, Elena I Sinauridze, Sergey I Obydennyi, Igor I Kireev, Fazoil I Ataullakhanov, Yuriy G Kaminsky
Erythrocytes (RBCs) loaded with alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALD) can metabolize plasma ethanol and acetaldehyde but with low efficiency. We investigated the rate-limiting factors in ethanol oxidation by these enzymes loaded into RBCs. Mathematical modeling and in vitro experiments on human RBCs loaded simultaneously with ADH and ALD (by hypoosmotic dialysis) were performed. The simulation showed that the rate of nicotinamide-adenine dinucleotide (NAD(+)) generation in RBC glycolysis, but not the activities of the loaded enzymes, is the rate-limiting step in external ethanol oxidation...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28642128/immunomodulation-of-parkinson-s-disease-using-mucuna-pruriens-mp
#9
REVIEW
Sachchida Nand Rai, Hareram Birla, Walia Zahra, Saumitra Sen Singh, Surya Pratap Singh
Immune control is associated with nigrostriatal neuroprotection for Parkinson's disease (PD); though its direct cause and effect relationships have not yet been realized and modulating the immune system for therapeutic gain has been openly discussed. While the pathobiology of PD remains in study, neuroinflammation is thought to speed nigrostriatal degeneration. The neuroinflammatory cascade associated with PD begins with aggregation of misfolded or post-translationally modified α-synuclein (α-syn). Such aggregation results in neuronal cell death and the presence of chronically activated glia (microglia and astroglia), leading to the production of proinflammatory cytokines like tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, and enzymes such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and cyclooxygenase-2 (COX-2)...
June 19, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28640982/mechanisms-of-sphingosine-1-phosphate-mediated-vasoconstriction-of-rat-afferent-arterioles
#10
Zhengrong Guan, Fuchenchu Wang, Xiangqin Cui, Edward W Inscho
AIM: Sphingosine-1-phosphate (S1P) influences resistance vessel function and is implicated in renal pathological processes. Previous studies revealed that S1P evoked potent vasoconstriction of the preglomerular microvasculature, but the underlying mechanisms remain incompletely defined. We postulated that S1P-mediated preglomerular microvascular vasoconstriction involves activation of voltage-dependent L-type calcium channels (L-VDCC) and the rho/rho kinase pathway. METHODS: Afferent arteriolar reactivity was assessed in vitro using the blood-perfused rat juxtamedullary nephron preparation and diameter was measured during exposure to physiological and pharmacological agents...
June 22, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28640881/t3ss-effector-vopl-inhibits-the-host-ros-response-promoting-the-intracellular-survival-of-vibrio-parahaemolyticus
#11
Marcela de Souza Santos, Dor Salomon, Kim Orth
The production of antimicrobial reactive oxygen species by the nicotinamide dinucleotide phosphate (NADPH) oxidase complex is an important mechanism for control of invading pathogens. Herein, we show that the gastrointestinal pathogen Vibrio parahaemolyticus counteracts reactive oxygen species (ROS) production using the Type III Secretion System 2 (T3SS2) effector VopL. In the absence of VopL, intracellular V. parahaemolyticus undergoes ROS-dependent filamentation, with concurrent limited growth. During infection, VopL assembles actin into non-functional filaments resulting in a dysfunctional actin cytoskeleton that can no longer mediate the assembly of the NADPH oxidase at the cell membrane, thereby limiting ROS production...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28640600/horse-liver-alcohol-dehydrogenase-zinc-coordination-and-catalysis
#12
Bryce V Plapp, Baskar Raj Savarimuthu, Daniel J Ferraro, Jon K Rubach, Eric N Brown, Subramanian Ramaswamy
: During catalysis by liver alcohol dehydrogenase (ADH), a water bound to the catalytic zinc is replaced by the oxygen of the substrates. The mechanism may involve a pentacoordinated zinc or a double displacement reaction with participation by a nearby glutamate residue, as suggested by studies of human ADH3, yeast ADH1 and some other tetrameric ADHs. Zinc coordination and participation of water in the enzyme mechanism were investigated by X-ray crystallography. Apoenzyme and its complex with adenosine 5'-diphosphoribose have an open protein conformation with the catalytic zinc in one position, tetracoordinated by Cys-46, His-67, Cys-174 and a water molecule...
June 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/28639913/novel-roles-of-folic-acid-as-redox-regulator-modulation-of-reactive-oxygen-species-sinker-protein-expression-and-maintenance-of-mitochondrial-redox-homeostasis-on-hepatocellular-carcinoma
#13
Kun-Goung Lai, Chi-Fen Chen, Chun-Te Ho, Jun-Jen Liu, Tsan-Zon Liu, Chi-Liang Chern
We provide herein several lines of evidence to substantiate that folic acid (or folate) is a micronutrient capable of functioning as a novel redox regulator on hepatocellular carcinoma. First, we uncovered that folate deficiency could profoundly downregulate two prominent anti-apoptotic effectors including survivin and glucose-regulated protein-78. Silencing of either survivin or glucose-regulated protein-78 via small interfering RNA interfering technique established that both effectors could serve as reactive oxygen species sinker proteins...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28639258/tandem-in-situ-monitoring-for-quantitative-assessment-of-mechanochemical-reactions-involving-structurally-unknown-phases
#14
Stipe Lukin, Tomislav Stolar, Martina Tireli, Maria Blanco, Darko Babić, Tomislav Friščić, Krunoslav Užarević, Ivan Halasz
Despite recent advances in real-time and in situ monitoring techniques, a thorough mechanistic understanding of mechanochemical milling reactions is often hindered by the inability of their quantitative evaluation. Here, a tandem approach combining in situ powder X-ray diffraction and Raman spectroscopy enabled quantitative assessment and kinetic analysis of mechanochemical reaction, even when involving new phases of unknown crystal structures, and short-lived intermediates. We also introduce in situ Raman monitoring as a standalone laboratory technique for quantitative assessment of mechanochemical reactions...
June 22, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28637419/pharmacological-inhibitors-of-nad-biosynthesis-as-potential-anticancer-agents
#15
Stephanie Lucas, Claire Soave, Gazal Nabil, Zainab Ahmed, Guohua Chen, Hossny El-Banna, Q Ping Dou, Jian Wang
BACKGROUND: Alteration of cellular metabolism is a hallmark of cancer, which underlies exciting opportunities to develop effective, anti-cancer therapeutics by targeting through inhibition of cancer metabolism. Nicotinamide adenine dinucleotide (NAD+), an essential coenzyme of energy metabolism and a signaling molecule linking cellular energy status to a spectrum of molecular regulation, has been shown to be in high demand in a variety of cancer cells. Depletion of NAD+ by inhibition of its key biosynthetic enzymes has become an attractive strategy to target cancer...
June 19, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/28634829/potential-inhibitory-effect-of-indolizine-derivatives-on-the-two-enzymes-nicotinamide-phosphoribosyltransferase-and-beta-lactamase-a-molecular-dynamics-study
#16
Beata Szefler, Przemysław Czeleń
Nicotinamide phosphoribosyl-transferases (NAMPT) are enzymes that play a role in targeting cancer metabolism, while beta lactamases are involved in bacterial resistance to beta-lactam antibiotics. Many protein inhibitors exhibit such property which is often correlated with their cellular potency. In order to understand such a phenomenon, the present article conducts an analysis of the dynamic behavior of complexes formed by the inhibitors, that is indolizine derivatives, with the studied enzymes. Both docking and molecular dynamics led to identification of their interactions and showed the mechanism of inhibition of the two studied enzymes...
July 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28633997/nicotinamide-inhibits-the-growth-of-p-falciparum-and-enhances-the-antimalarial-effect-of-artemisinin-chloroquine-and-pyrimethamine
#17
Sergey O Tcherniuk, Olga Chesnokova, Irina V Oleinikov, Andrew V Oleinikov
Nicotinamide (vitamin B3) - is a water soluble amide derivative of nicotinic acid, which has been used at high doses for a variety of therapeutic applications. However, its antimalarial effect has not been intensively explored. In this work we analysed the effect of nicotinamide alone and in combination with artemisinin, chloroquine andpyrimethamine on the growth of blood stages of P. falciparum. Our results demonstrate that nicotinamide effectively inhibits the growth of blood stage parasites with IC50 of 6...
June 19, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28632450/combinations-of-activin-a-or-nicotinamide-with-the-pancreatic-transcription-factor-pdx1-support-differentiation-of-human-amnion-epithelial-cells-toward-a-pancreatic-lineage
#18
Shruti Balaji, Yu Zhou, Emmanuel C Opara, Shay Soker
The differentiation of multipotent stem cells toward a pancreatic lineage provides us with an alternative cell-based therapeutic approach to type 1 diabetes and enables us to study pancreas development. The current study aims to study the effect of growth factors such as activin A or nicotinamide, alone and in combinations with the transcription factor, PDX1 (pancreatic and duodenal homeobox-1), on human amnion epithelial cells (hAECs) toward a pancreatic lineage. Ectopic expression of Pdx1 followed by treatment of hAECs with nicotinamide for 4 days resulted in strong induction of pancreatic endoderm and pancreatic progenitor genes, including NKX6...
June 20, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28631861/renewable-molecular-flasks-with-nadh-models-combination-of-light-driven-proton-reduction-and-biomimetic-hydrogenation-of-benzoxazinones
#19
Liang Zhao, Jianwei Wei, Junhua Lu, Cheng He, Chunying Duan
Using small molecules with defined pockets to catalyze chemical transformations resulted in attractive catalytic syntheses that echo the remarkable properties of enzymes. By modulating the active site of a nicotinamide adenine dinucleotide (NADH) model in a redox-active molecular flask, we combined biomimetic hydrogenation with in situ regeneration of the active site in a one-pot transformation using light as a clean energy source. This molecular flask facilitates the encapsulation of benzoxazinones for biomimetic hydrogenation of the substrates within the inner space of the flask using the active sites of the NADH models...
June 20, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28631256/vulnerability-to-a-metabolic-challenge-following-perinatal-asphyxia-evaluated-by-organotypic-cultures-neonatal-nicotinamide-treatment
#20
R Perez-Lobos, C Lespay-Rebolledo, A Tapia-Bustos, E Palacios, V Vío, D Bustamante, P Morales, M Herrera-Marschitz
The hypothesis of enhanced vulnerability following perinatal asphyxia was investigated with a protocol combining in vivo and in vitro experiments. Asphyxia-exposed (AS) (by 21 min water immersion of foetuses containing uterine horns) and caesarean-delivered control (CS) rat neonates were used at P2-3 for preparing triple organotypic cultures (substantia nigra, neostriatum and neocortex). At DIV 18, cultures were exposed to different concentrations of H2O2 (0.25-45 mM), added to the culture medium for 18 h...
June 19, 2017: Neurotoxicity Research
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