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https://www.readbyqxmd.com/read/28220827/anti-inflammatory-and-anti-excitoxic-effects-of-diethyl-oxopropanamide-an-ethyl-pyruvate-bioisoster-exert-robust-neuroprotective-effects-in-the-postischemic-brain
#1
Hye-Kyung Lee, Il-Doo Kim, Seung-Woo Kim, Hahnbie Lee, Ju-Young Park, Sung-Hwa Yoon, Ja-Kyeong Lee
Ethyl pyruvate (EP) is a simple aliphatic ester of pyruvic acid and has been shown to have robust neuroprotective effects via its anti-inflammatory, anti-oxidative, and anti-apoptotic functions. In an effort to develop novel EP derivatives with greater protective potencies than EP, we generated four EP isosteres, among them the neuroprotective potency of N,N-diethyl-2-oxopropanamide (DEOPA), in which the ethoxy group of EP was replaced with diethylamine, was far greater than that of EP. When DEOPA was administered intravenously (5 mg/kg) to rat middle cerebral artery occlusion (MCAO) model at 6 hrs post-surgery, it suppressed infarct formation, ameliorated neurological and sensory/motor deficits, and inhibited microglial activation and neutrophil infiltrations in the postischemic brain more effectively than EP...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220528/enzymatic-characterization-and-functional-implication-of-two-structurally-different-isocitrate-dehydrogenases-from-xylella-fastidiosa
#2
Peipei Lv, Wanggang Tang, Peng Wang, Zhengyu Cao, Guoping Zhu
Isocitrate dehydrogenase (IDH) is a key enzyme at the critical junction between the tricarboxylic acid cycle and the glyoxylate cycle. Most bacteria have only one IDH, while a few of bacteria contain two IDH isozymes. The coexistence of two different type IDHs in one organism was little known. Xylella fastidiosa is a nutritionally fastidious plant pathogen that contains two structurally different IDHs, an NAD(+) -dependent homodimeric IDH (diXfIDH) and an NADP(+) -dependent monomeric IDH (monoXfIDH). Kinetic characterization showed that diXfIDH displayed 206-fold preferences for NAD(+) over NADP(+) , while monoXfIDH showed 13800-fold preferences for NADP(+) over NAD(+) ...
February 21, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28219011/inhibition-of-the-aldehyde-dehydrogenase-1-2-family-by-psoralen-and-coumarin-derivatives
#3
Cameron D Buchman, Thomas D Hurley
Aldehyde dehydrogenase 2 (ALDH2), one of 19 ALDH superfamily members, catalyzes the NAD+-dependent oxidation of aldehydes to their respective carboxylic acids. In this study, we further characterized the inhibition of four psoralen and coumarin derivatives towards ALDH2 and compared them to the ALDH2 inhibitor daidzin for selectivity against five ALDH1/2 isoenzymes. Compound 2 (Ki=19 nM) binds within the aldehyde-binding site of the free enzyme species of ALDH2. Thirty-three structural analogs were examined to develop a stronger SAR profile...
February 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28217084/nad-attenuates-bilirubin-induced-hyperexcitation-in-the-ventral-cochlear-nucleus-by-inhibiting-excitatory-neurotransmission-and-neuronal-excitability
#4
Min Liang, Xin-Lu Yin, Lu-Yang Wang, Wei-Hai Yin, Ning-Ying Song, Hai-Bo Shi, Chun-Yan Li, Shan-Kai Yin
Nicotinamide adenine dinucleotide (NAD+) is an important molecule with extensive biological functions in various cellular processes, including protection against cell injuries. However, little is known regarding the roles of NAD+ in neuronal excitation and excitotoxicity associated with many neurodegenerative disorders and diseases. Using patch-clamp recordings, we studied its potential effects on principal neurons in the ventral cochlear nucleus (VCN), which is particularly vulnerable to bilirubin excitotoxicity...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28216341/mechanisms-of-protection-against-irreversible-oxidation-of-the-catalytic-cysteine-of-aldh-enzymes-possible-role-of-vicinal-cysteines
#5
Rosario A Muñoz-Clares, Lilian González-Segura, Dario S Murillo-Melo, Héctor Riveros-Rosas
The catalytic mechanism of the NAD(P)(+)-dependent aldehyde dehydrogenases (ALDHs) involves the nucleophilic attack of the essential cysteine (Cys302, mature HsALDH2 numbering) on the aldehyde substrate. Although oxidation of Cys302 will inactivate these enzymes, it is not yet well understood how this oxidation is prevented. In this work we explore possible mechanisms of protection by systematically analyzing the reported three-dimensional structures and amino acid sequences of the enzymes of the ALDH superfamily...
February 16, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28216063/the-nad-precursor-nicotinic-acid-improves-genomic-integrity-in-human-peripheral-blood-mononuclear-cells-after-x-irradiation
#6
Kathrin Weidele, Sascha Beneke, Alexander Bürkle
NAD(+) is an essential cofactor for enzymes catalyzing redox-reactions as well as an electron carrier in energy metabolism. Aside from this, NAD(+) consuming enzymes like poly(ADP-ribose) polymerases and sirtuins are important regulators involved in chromatin-restructuring processes during repair and epigenetics/transcriptional adaption. In order to replenish cellular NAD(+) levels after cleavage, synthesis starts from precursors such as nicotinamide, nicotinamide riboside or nicotinic acid to match the need for this essential molecule...
February 13, 2017: DNA Repair
https://www.readbyqxmd.com/read/28214984/dl-3-n-butylphthalide-nbp-provides-neuroprotection-in-the-mice-models-after-traumatic-brain-injury-via-nrf2-are-signaling-pathway
#7
Zhengwei Liu, Handong Wang, Xiaofeng Shi, Liwen Li, Mengliang Zhou, Hui Ding, Youqing Yang, Xiang Li, Ke Ding
The present study was aimed to evaluate the neuroprotective effects of NBP in the mice models of TBI, as well as the possible role of Nrf2-ARE pathways in the assumptive neuroprotection. In mice,a modified Marmarou's weight-drop model was employed to induce TBI. ICR mice were randomly assigned to four experimental groups: sham, TBI, TBI+vehicle(V) and TBI+NBP. NBP (100 mg/kg) was administered via an intraperitoneal (i.p.) injection at 1 h following TBI. The administration of NBP significantly ameliorated the effects of the brain injury, including neurological deficits, brain water content, and cortical neuronal apoptosis...
February 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28214861/sirt1-regulates-the-inflammatory-response-of-vascular-adventitial-fibroblasts-through-autophagy-and-related-signaling-pathway
#8
Wei-Rong Wang, Ting-Ting Li, Ting Jing, Yan-Xiang Li, Xiao-Feng Yang, Yan-Hao He, Wei Zhang, Rong Lin, Ji-Ye Zhang
BACKGROUND/AIMS: Autophagy is a lysosomal degradation pathway that is essential for cellular survival, differentiation, and homeostasis. Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, plays a pivotal role in modulation of autophagy. Recent studies found that autophagy was involved in the regulation of inflammatory response. In this study, we aimed to determine the effect of SIRT1 on autophagy and inflammation, and whether autophagy can regulate the inflammatory response in vascular adventitial fibroblasts (VAFs)...
February 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28211759/gamma-tocopherol-supplementation-ameliorated-hyper-inflammatory-response-during-the-early-cutaneous-wound-healing-in-alloxan-induced-diabetic-mice
#9
Jihyun Shin, Soo Jin Yang, Yunsook Lim
Delayed wound healing is one of the major diabetic complications. During wound healing process, the early inflammatory stage is important for better prognosis. One of antioxidant nutrient, gamma-tocopherol (GT) is considered to regulate inflammatory conditions. This study investigated the effect of GT supplementation on mechanism associated with inflammation, oxidative stress, and apoptosis during early cutaneous wound healing in diabetic mice. Diabetes was induced by alloxan injection in ICR mice. All mice were divided into three groups: non-diabetic control mice (CON), diabetic control mice (DMC), and diabetic mice supplemented with GT (GT)...
March 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28209901/vitamin-b3-modulates-mitochondrial-vulnerability-and-prevents-glaucoma-in-aged-mice
#10
Pete A Williams, Jeffrey M Harder, Nicole E Foxworth, Kelly E Cochran, Vivek M Philip, Vittorio Porciatti, Oliver Smithies, Simon W M John
Glaucomas are neurodegenerative diseases that cause vision loss, especially in the elderly. The mechanisms initiating glaucoma and driving neuronal vulnerability during normal aging are unknown. Studying glaucoma-prone mice, we show that mitochondrial abnormalities are an early driver of neuronal dysfunction, occurring before detectable degeneration. Retinal levels of nicotinamide adenine dinucleotide (NAD(+), a key molecule in energy and redox metabolism) decrease with age and render aging neurons vulnerable to disease-related insults...
February 17, 2017: Science
https://www.readbyqxmd.com/read/28208702/the-glutamate-dehydrogenase-pathway-and-its-roles-in-cell-and-tissue-biology-in-health-and-disease
#11
REVIEW
Andreas Plaitakis, Ester Kalef-Ezra, Dimitra Kotzamani, Ioannis Zaganas, Cleanthe Spanaki
Glutamate dehydrogenase (GDH) is a hexameric enzyme that catalyzes the reversible conversion of glutamate to α-ketoglutarate and ammonia while reducing NAD(P)⁺ to NAD(P)H. It is found in all living organisms serving both catabolic and anabolic reactions. In mammalian tissues, oxidative deamination of glutamate via GDH generates α-ketoglutarate, which is metabolized by the Krebs cycle, leading to the synthesis of ATP. In addition, the GDH pathway is linked to diverse cellular processes, including ammonia metabolism, acid-base equilibrium, redox homeostasis (via formation of fumarate), lipid biosynthesis (via oxidative generation of citrate), and lactate production...
February 8, 2017: Biology
https://www.readbyqxmd.com/read/28207859/differential-effects-of-silencing-crustacean-hyperglycemic-hormone-gene-expression-on-the-metabolic-profiles-of-the-muscle-and-hepatopancreas-in-the-crayfish-procambarus-clarkii
#12
Wenfeng Li, Kuo-Hsun Chiu, Yi-Chun Tien, Shih-Fu Tsai, Li-Jane Shih, Chien-Hsun Lee, Jean-Yves Toullec, Chi-Ying Lee
In order to functionally characterize the metabolic roles of crustacean hyperglycemic hormone (CHH), gene expression of CHH in the crayfish (Procambarus clarkii) was knocked down by in vivo injection of CHH double-stranded RNA (dsRNA), followed by metabolomic analysis of 2 CHH target tissues (the muscle and hepatopancreas) using nuclear magnetic resonance spectroscopy. Compared to the levels in untreated and saline-injected (SAI) animals, levels of CHH transcript, but not those of molt-inhibiting hormone (a CHH-family peptide), in the eyestalk ganglia of CHH dsRNA-injected (DSI) animals were significantly decreased at 24, 48, and 72 hour post injection (hpi), with concomitant changes in levels of CHH peptide in the sinus gland (a neurohemal organ) and hemolymph...
2017: PloS One
https://www.readbyqxmd.com/read/28203294/correlation-between-nad-p-h-quinone-oxidoreductase-1-c609t-polymorphism-and-increased-risk-of-esophageal-cancer-evidence-from-a-meta-analysis
#13
Jingfang Diao, Jie Bao, Jianxin Peng, Jiaqiang Mo, Qing Ye, Junming He
NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T gene polymorphisms have been reported to influence the risk for esophageal cancer (EC) in many studies. However, the results remain controversial and ambiguous. We performed a meta-analysis, which included 13 independent studies with a total of 2357 subjects, to examine the association between NQO1 C609T polymorphism and EC. The association was assessed by five different gene models. The overall analysis suggested that the variant allele and genotypes were significantly related to increased risk of EC (odds ratio [OR] T versus C = 1...
January 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28202712/ribeye-b-domain-binds-to-lipid-components-of-synaptic-vesicles-in-an-nad-h-dependent-redox-sensitive-manner
#14
Karin Schwarz, Frank Schmitz
Synaptic ribbons are needed for fast and continuous exocytosis in ribbon synapses. RIBEYE is a main protein component of synaptic ribbons and necessary to build the synaptic ribbon. RIBEYE consists of a unique A-domain and a carboxyterminal B-domain that binds NAD(H). Within the presynaptic terminal, the synaptic ribbons are in physical contact with large numbers of synaptic vesicles. How this physical contact between ribbons and vesicles is established at a molecular level is not well understood. In the present study, we demonstrate that the RIBEYE(B)-domain can directly interact with lipid components of synaptic vesicles using two different sedimentation assays with liposomes of defined chemical composition...
February 15, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28202508/chemosensitivity-of-idh1-mutant-gliomas-due-to-an-impairment-in-parp1-mediated-dna-repair
#15
Yanxin Lu, Jakub Kwintkiewicz, Yang Liu, Katherine Tech, Lauren N Frady, Yu-Ting Su, Wendy Bautista, Seog In Moon, Jeffrey MacDonald, Matthew G Edwend, Mark R Gilbert, Chunzhang Yang, Jing Wu
Mutations in isocitrate dehydrogenase (IDH) are the most prevalent genetic abnormalities in lower grade gliomas. The presence of these mutations in glioma is prognostic for better clinical outcomes with longer patient survival. In the present study, we found that defects in oxidative metabolism and 2-HG production confer chemosensitization in IDH1-mutated glioma cells. In addition, temozolomide (TMZ) treatment induced greater DNA damage and apoptotic changes in mutant glioma cells. The PARP1-associated DNA repair pathway was extensively compromised in mutant cells due to decreased NAD+ availability...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28202489/nicotinamide-phosphoribosyltransferase-promotes-pulmonary-vascular-remodeling-and-is-a-therapeutic-target-in-pulmonary-arterial-hypertension
#16
Jiwang Chen, Justin R Sysol, Sunit Singla, Shuangping Zhao, Aya Yamamura, Daniela Valdez-Jasso, Taimur Abbasi, Krystyna M Shioura, Sakshi Sahni, Vamsi Reddy, Arvind Sridhar, Hui Gao, Jaime Torres, Sara M Camp, Haiyang Tang, Shui Quing Ye, Suzy Comhair, Raed Dweik, Paul Hassoun, Jason X-J Yuan, Joe G N Garcia, Roberto F Machado
Background -Pulmonary arterial hypertension (PAH) is a severe and progressive disease, a hallmark of which is pulmonary vascular remodeling. Nicotinamide phosphoribosyltransferase (NAMPT), is a cytozyme which regulates intracellular NAD levels and cellular redox state, regulates histone deacetylases, promotes cell proliferation and inhibits apoptosis. We hypothesized that NAMPT promotes pulmonary vascular remodeling, and that inhibition of NAMPT could attenuate pulmonary hypertension. Methods -Plasma and mRNA and protein levels of NAMPT were measured in the lungs and isolated pulmonary artery endothelial cells (PAECs) from PAH patients, as well as in lungs of rodent models of pulmonary hypertension (PH)...
February 15, 2017: Circulation
https://www.readbyqxmd.com/read/28199340/crystal-structure-and-structure-based-mutagenesis-of-actin-specific-adp-ribosylating-toxin-cpile-a-as-novel-enterotoxin
#17
Waraphan Toniti, Toru Yoshida, Toshiharu Tsurumura, Daisuke Irikura, Chie Monma, Yoichi Kamata, Hideaki Tsuge
Unusual outbreaks of food poisoning in Japan were reported in which Clostridium perfringens was strongly suspected to be the cause based on epidemiological information and fingerprinting of isolates. The isolated strains lack the typical C. perfringens enterotoxin (CPE) but secrete a new enterotoxin consisting of two components: C. perfringens iota-like enterotoxin-a (CPILE-a), which acts as an enzymatic ADP-ribosyltransferase, and CPILE-b, a membrane binding component. Here we present the crystal structures of apo-CPILE-a, NAD+-CPILE-a and NADH-CPILE-a...
2017: PloS One
https://www.readbyqxmd.com/read/28198851/interrogation-of-metabolic-and-oxygen-states-of-tumors-with-fiber-based-luminescence-lifetime-spectroscopy
#18
Maria Lukina, Anna Orlova, Marina Shirmanova, Daniil Shirokov, Anton Pavlikov, Antje Neubauer, Hauke Studier, Wolfgang Becker, Elena Zagaynova, Toshitada Yoshihara, Seiji Tobita, Vladislav Shcheslavskiy
The study of metabolic and oxygen states of cells in a tumor in vivo is crucial for understanding of the mechanisms responsible for tumor development and provides background for the relevant tumor's treatment. Here, we show that a specially designed implantable fiber-optic probe provides a promising tool for optical interrogation of metabolic and oxygen states of a tumor in vivo. In our experiments, the excitation light from a ps diode laser source is delivered to the sample through an exchangeable tip via a multimode fiber, and the emission light is transferred to the detector by another multimode fiber...
February 15, 2017: Optics Letters
https://www.readbyqxmd.com/read/28198668/comparative-analysis-of-corynebacterium-glutamicum-genomes-a-new-perspective-for-the-industrial-production-of-amino-acids
#19
Junjie Yang, Sheng Yang
BACKGROUND: Corynebacterium glutamicum is a non-pathogenic bacterium widely used in industrial amino acid production and metabolic engineering research. Although the genome sequences of some C. glutamicum strains are available, comprehensive comparative genome analyses of these species have not been done. Six wild type C. glutamicum strains were sequenced using next-generation sequencing technology in our study. Together with 20 previously reported strains, we present a comprehensive comparative analysis of C...
January 25, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28197299/sirtuins-expression-and-their-role-in-retinal-diseases
#20
REVIEW
Sankarathi Balaiya, Khaled K Abu-Amero, Altaf A Kondkar, Kakarla V Chalam
Sirtuins have received considerable attention since the discovery that silent information regulator 2 (Sir2) extends the lifespan of yeast. Sir2, a nicotinamide adenine dinucleotide- (NAD-) dependent histone deacetylase, serves as both a transcriptional effector and energy sensor. Oxidative stress and apoptosis are implicated in the pathogenesis of neurodegenerative eye diseases. Sirtuins confer protection against oxidative stress and retinal degeneration. In mammals, the sirtuin (SIRT) family consists of seven proteins (SIRT1-SIRT7)...
2017: Oxidative Medicine and Cellular Longevity
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