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https://www.readbyqxmd.com/read/28741793/telomerase-enzyme-deficiency-promotes-metabolic-dysfunction-in-murine-hepatocytes-upon-dietary-stress
#1
Raquel M Alves-Paiva, Sachiko Kajigaya, Xingmin Feng, Jichun Chen, Marie Desierto, Susan Wong, Danielle M Townsley, Flávia S Donaires, Adeline Bertola, Bin Gao, Neal S Young, Rodrigo T Calado
Short telomeres and genetic telomerase defects are risk factors for some human liver diseases, ranging from non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) to cirrhosis. In murine models, telomere dysfunction has been shown to metabolically compromise hematopoietic cells, liver, and heart via the activation of the p53-PGC axis METHODS: Tert- and Terc-deficient mice were challenged with liquid high fat diet (HFD). Liver metabolic contents were analyzed by CE-TOFMS and liver fat content was confirmed by confocal and electronic microscopy RESULTS: Tert-deficient but not Terc-deficient mice develop hepatocyte injury and frank steatosis when challenged with liquid HFD...
July 25, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28740668/socioeconomic-impact-of-asthma-chronic-obstructive-pulmonary-disease-and-asthma-copd-overlap-syndrome
#2
Jinhee Kim, Young Sam Kim, Kyungjoo Kim, Yeon-Mok Oh, Kwang Ha Yoo, Chin Kook Rhee, Jin Hwa Lee
BACKGROUND: Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is defined as having both features of asthma and COPD, which are airway hyper-responsiveness and incompletely reversible airway obstruction. However, socioeconomic impact of ACOS have not been well appreciated. METHODS: Adults with available wheezing history and acceptable spirometry were selected from the fourth Korean National Health and Nutrition Examination Survey (KNHANES IV) in 2007-2009...
June 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28739840/mitochondrial-sirtuins-in-cardiometabolic-diseases
#3
REVIEW
Xiaoqiang Tang, Xiao-Feng Chen, Hou-Zao Chen, De-Pei Liu
Mitochondria are heterogeneous and essentially contribute to cellular functions and tissue homeostasis. Mitochondrial dysfunction compromises overall cell functioning, tissue damage, and diseases. The advances in mitochondrion biology increase our understanding of mitochondrial dynamics, bioenergetics, and redox homeostasis, and subsequently, their functions in tissue homeostasis and diseases, including cardiometabolic diseases (CMDs). The functions of mitochondria mainly rely on the enzymes in their matrix...
August 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28739597/a-large-deletion-in-the-nsdhl-gene-in-labrador-retrievers-with-a-congenital-cornification-disorder
#4
Anina Bauer, Michela De Lucia, Vidhya Jagannathan, Giorgia Mezzalira, Margaret L Casal, Monika M Welle, Tosso Leeb
In heterozygous females affected by an X-linked skin disorder, lesions often appear in a characteristic pattern, the so-called Blaschko's lines. We investigated a female Labrador Retriever and her crossbred daughter, which both showed similar clinical lesions that followed Blaschko's lines. The two male littermates of the affected daughter had died at birth suggesting a monogenic X-chromosomal semi-dominant mode of inheritance. Whole genome sequencing of the affected daughter and subsequent automated variant filtering with respect to 188 non-affected control dogs of different breeds revealed 332 heterozygous variants on the X-chromosome private to the affected dog...
July 24, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28736552/asiatic-acid-exhibits-anti-inflammatory-and-antioxidant-activities-against-lipopolysaccharide-and-d-galactosamine-induced-fulminant-hepatic-failure
#5
Hongming Lv, Zhimin Qi, Sisi Wang, Haihua Feng, Xuming Deng, Xinxin Ci
Inflammation and oxidative stress are essential for the pathogenesis of fulminant hepatic failure (FHF). Asiatic acid (AA), which is a pentacyclic triterpene that widely occurs in various vegetables and fruits, has been reported to possess antioxidant and anti-inflammatory properties. In this study, we investigated the protective effects of AA against lipopolysaccharide (LPS) and d-galactosamine (GalN)-induced FHF and the underlying molecular mechanisms. Our findings suggested that AA treatment effectively protected against LPS/d-GalN-induced FHF by lessening the lethality; decreasing the alanine transaminase and aspartate aminotransferase levels, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α production, malondialdehyde formation, myeloperoxidase level and reactive oxygen species generation (i...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28736426/modulation-of-mitochondrial-membrane-potential-and-ros-generation-by-nicotinamide-in-a-manner-independent-of-sirt1-and-mitophagy
#6
Seon Beom Song, So-Young Jang, Hyun Tae Kang, Bie Wei, Un-Woo Jeoun, Gye Soon Yoon, Eun Seong Hwang
Nicotinamide (NAM) plays essential roles in physiology through facilitating NAD+ redox homeostasis. Importantly, at high doses, it protects cells under oxidative stresses, and has shown therapeutic effectiveness in a variety of disease conditions. In our previous studies, NAM lowered reactive oxygen species (ROS) levels and extended cellular life span in primary human cells. In the treated cells, levels of NAD+/NADH and SIRT1 activity increased, while mitochondrial content decreased through autophagy activation...
July 31, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28736243/from-insulin-synthesis-to-secretion-alternative-splicing-of-type-2-ryanodine-receptor-gene-is-essential-for-insulin-secretion-in-pancreatic-%C3%AE-cells
#7
Hiroshi Okamoto, Shin Takasawa, Yasuhiko Yamamoto
Increases in the intracellular Ca(2+) concentration in pancreatic islets, resulting from the its mobilization from the intracellular source through the ryanodine receptor, are essential for insulin secretion by glucose. Cyclic ADP-ribose, a potent Ca(2+) mobilizing second messenger synthesized from NAD(+) by CD38, regulates the opening of ryanodine receptor. A novel ryanodine receptor mRNA (the islet-type ryanodine receptor) was found to be generated from the type 2 ryanodine receptor gene by the alternative splicing of exons 4 and 75...
July 20, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28733523/preclinical-efficacy-of-the-novel-competitive-nampt-inhibitor-stf-118804-in-pancreatic-cancer
#8
Jair Machado Espindola-Netto, Claudia C S Chini, Mariana Tarragó, Enfeng Wang, Shamit Dutta, Krishnendu Pal, Debabrata Mukhopadhyay, Mauro Sola-Penna, Eduardo N Chini
NAD salvage is one of the pathways used to generate NAD in mammals. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in this pathway, uses nicotinamide (NAM) to generate nicotinamide mononucleotide (NMN). NMN is one of the main precursors of NAD synthesis in cells. Our previous study showed the importance of NAMPT in maintaining NAD levels in pancreatic ductal adenocarcinoma cells (PDAC), and that the NAMPT inhibitor FK866 decreased pancreatic cancer growth. We now tested the effect of STF-118804, a new highly specific NAMPT inhibitor, in models of pancreatic ductal adenocarcinoma...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733231/tussilagonone-induced-nrf2-pathway-activation-protects-hepg2-cells-from-oxidative-injury
#9
Kyung-Mi Lee, Tae Yeon Kwon, Unwoo Kang, Eun Kyoung Seo, Ji Ho Yun, Chu Won Nho, Yeong Shik Kim
Tussilagonone is a compound derived from the medicinal plant Tussilago farfara L., which is used as a traditional medicine for respiratory diseases, including asthma and pneumonia. Recent reports suggest that tussilagonone exhibits anti-inflammatory effects; however, the scope of protective functions has not been elucidated yet. In this study, we demonstrate that tussilagonone enhances cellular detoxification by increasing quinone reductase activity in Hepa1c1c7 cells. In addition, tussilagonone decreased tert-butyl hydroperoxide(t-BHP)-induced ROS production and cell death, suggesting that it also acts as a potent antioxidant...
July 18, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28732729/crystal-structures-of-an-atypical-aldehyde-dehydrogenase-having-bidirectional-oxidizing-and-reducing-activities
#10
Kyoungho Jung, Seung-Hye Hong, Ho-Phuong-Thuy Ngo, Thien-Hoang Ho, Yeh-Jin Ahn, Deok-Kun Oh, Lin-Woo Kang
Aldehyde dehydrogenases (ALDHs) are NAD(P)(+)-dependent oxidoreductases that catalyze the oxidation of a variety of aldehydes to their acid forms. In this study, we determined the crystal structures of ALDH from Bacillus cereus (BcALDH), alone, and in complex with NAD(+) and NADP(+). This enzyme can oxidize all-trans-retinal to all-trans-retinoic acid using either NAD(+) or NADP(+) with equal efficiency, and atypically, as a minor activity, can reduce all-trans-retinal to all-trans-retinol using NADPH. BcALDH accommodated the additional 2'-phosphate of NADP(+) by expanding the cofactor-binding pocket and upshifting the AMP moiety in NADP(+)...
July 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28731346/kinetics-of-light-induced-intramolecular-energy-transfer-in-different-conformational-states-of-nadh
#11
Zsuzsanna Heiner, Thomas Roland, Jérémie Léonard, Stefan Haacke, Géza I Groma
When bound to a protein, the coenzyme NAD+/NADH typically exists in an extended conformation, while in aqueous solutions it can be characterized by an equilibrium of folded and unfolded structures. It was recognized long ago that in the folded conformation light absorption at the adenine ring initiates an effective energy transfer (ET) towards the nicotinamide group, but the mechanism of this process is still unexplored. Here we apply ultrafast transient absorption measurements on NADH combined with compartmental model analysis for following the kinetics of the ET...
July 21, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28728845/crystal-structure-of-cis-dihydrodiol-naphthalene-dehydrogenase-nahb-from-pseudomonas-sp-mc1-insights-into-the-early-binding-process-of-the-substrate
#12
Ae Kyung Park, Hyun Kim, Il-Sup Kim, Soo Jung Roh, Seung Chul Shin, Jun Hyuck Lee, Hyun Park, Han-Woo Kim
The bacterial strain Pseudomonas sp. MC1 harbors an 81-kb metabolic plasmid, which encodes enzymes involved in the conversion of naphthalene to salicylate. Of these, the enzyme NahB (cis-dihydrodiol naphthalene dehydrogenase), which catalyzes the second reaction of this pathway, binds to various substrates such as cis-1,2-dihydro-1,2-dihydroxy-naphthalene (1,2-DDN), cis-2,3-dihydro-2,3-dihydroxybiphenyl (2,3-DDB), and 3,4-dihydro-3,4-dihydroxy-2,2',5,5'-tetrachlorobiphenyl (3,4-DD-2,2',5-5-TCB). However, the mechanism underlying its broad substrate specificity is unclear owing to the lack of structural information...
July 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28724915/quinolinate-phosphoribosyltransferase-is-an-antiviral-host-factor-against-hepatitis-c-virus-infection
#13
Zhilong Wang, Yanhang Gao, Chao Zhang, Haiming Hu, Dongwei Guo, Yi Xu, Qiuping Xu, Weihong Zhang, Sisi Deng, Pingyun Lv, Yan Yang, Yanhua Ding, Qingquan Li, Changjiang Weng, Xinwen Chen, Sitang Gong, Hairong Chen, Junqi Niu, Hong Tang
HCV infection can decrease NAD(+)/NADH ratio, which could convert lipid metabolism to favor HCV replication. In hepatocytes, quinolinate phosphoribosyl transferase (QPRT) catabolizes quinolinic acid (QA) to nicotinic acid mononucleotide (NAMN) for de novo NAD synthesis. However, whether and how HCV modulates QPRT hence the lipogenesis is unknown. In this work, we found QPRT was reduced significantly in livers of patients or humanized C/O(Tg) mice with persistent HCV infection. Mechanistic studies indicated that HCV NS3/4A promoted proteasomal degradation of QPRT through Smurf2, an E3 ubiquitin-protein ligase, in Huh7...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724806/nicotinamide-mononucleotide-requires-sirt3-to-improve-cardiac-function-and-bioenergetics-in-a-friedreich-s-ataxia-cardiomyopathy-model
#14
Angelical S Martin, Dennis M Abraham, Kathleen A Hershberger, Dhaval P Bhatt, Lan Mao, Huaxia Cui, Juan Liu, Xiaojing Liu, Michael J Muehlbauer, Paul A Grimsrud, Jason W Locasale, R Mark Payne, Matthew D Hirschey
Increasing NAD+ levels by supplementing with the precursor nicotinamide mononucleotide (NMN) improves cardiac function in multiple mouse models of disease. While NMN influences several aspects of mitochondrial metabolism, the molecular mechanisms by which increased NAD+ enhances cardiac function are poorly understood. A putative mechanism of NAD+ therapeutic action exists via activation of the mitochondrial NAD+-dependent protein deacetylase sirtuin 3 (SIRT3). We assessed the therapeutic efficacy of NMN and the role of SIRT3 in the Friedreich's ataxia cardiomyopathy mouse model (FXN-KO)...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28724407/characterization-of-the-cytochrome-p450-monooxygenase-genes-p450ome-from-the-carotenogenic-yeast-xanthophyllomyces-dendrorhous
#15
Pamela Córdova, Ana-María Gonzalez, David R Nelson, María-Soledad Gutiérrez, Marcelo Baeza, Víctor Cifuentes, Jennifer Alcaíno
BACKGROUND: The cytochromes P450 (P450s) are a large superfamily of heme-containing monooxygenases involved in the oxidative metabolism of an enormous diversity of substrates. These enzymes require electrons for their activity, and the electrons are supplied by NAD(P)H through a P450 electron donor system, which is generally a cytochrome P450 reductase (CPR). The yeast Xanthophyllomyces dendrorhous has evolved an exclusive P450-CPR system that specializes in the synthesis of astaxanthin, a carotenoid with commercial potential...
July 19, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28722682/activation-of-the-nrf2-are-signaling-pathway-by-probucol-contributes-to-inhibiting-inflammation-and-neuronal-apoptosis-after-spinal-cord-injury
#16
Zipeng Zhou, Chang Liu, Shurui Chen, Haosen Zhao, Kang Zhou, Wei Wang, Yajiang Yuan, Zhuo Li, Yue Guo, Zhaoliang Shen, Xifan Mei
The nuclear erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway plays an essential role in the cellular antioxidant and anti-inflammatory responses. Spinal cord injury (SCI) results in a massive release of inflammatory factors and free radicals, which seriously compromise nerve recovery and axon regeneration. In this study, we examined the efficacy of probucol on anti-inflammatory responses and functional recovery after SCI by activating the Nrf2/ARE signaling pathway. We also investigated the mechanism by which inflammation is inhibited in this process...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722654/a-lectin-receptor-kinase-as-a-potential-sensor-for-extracellular-nicotinamide-adenine-dinucleotide-in-arabidopsis-thaliana
#17
Chenggang Wang, Mingqi Zhou, Xudong Zhang, Jin Yao, Yanping Zhang, Zhonglin Mou
Nicotinamide adenine dinucleotide (NAD(+)) participates in intracellular and extracellular signaling events unrelated to metabolism. In animals, purinergic receptors are required for extracellular NAD(+) (eNAD(+)) to evoke biological responses, indicating that eNAD(+) may be sensed by cell-surface receptors. However, the identity of eNAD(+)-binding receptors still remains elusive. Here, we identify a lectin receptor kinase (LecRK), LecRK-I.8, as a potential eNAD(+) receptor in Arabidopsis. The extracellular lectin domain of LecRK-I...
July 19, 2017: ELife
https://www.readbyqxmd.com/read/28721437/erk1-is-dispensable-for-mouse-pancreatic-beta-cell-function-but-is-necessary-for-glucose-induced-full-activation-of-msk1-and-creb
#18
Michele Leduc, Joy Richard, Safia Costes, Dany Muller, Annie Varrault, Vincent Compan, Julia Mathieu, Jean-François Tanti, Gilles Pagès, Jacques Pouyssegur, Gyslaine Bertrand, Stéphane Dalle, Magalie A Ravier
AIMS/HYPOTHESIS: Insufficient insulin secretion from pancreatic beta cells, which is associated with a decrease in beta cell mass, is a characteristic of type 2 diabetes. Extracellular signal-related kinase 1 and 2 (ERK1/2) inhibition in beta cells has been reported to affect insulin secretion, gene transcription and survival, although whether ERK1 and ERK2 play distinct roles is unknown. The aim of this study was to assess the individual roles of ERK1 and ERK2 in beta cells using ERK1 (also known as Mapk3)-knockout mice (Erk1 (-/-) mice) and pharmacological approaches...
July 18, 2017: Diabetologia
https://www.readbyqxmd.com/read/28720729/inhibition-of-inflammasome-dependent-interleukin-1%C3%AE-production-by-streptococcal-nad-glycohydrolase-evidence-for-extracellular-activity
#19
Dóra Hancz, Elsa Westerlund, Benedicte Bastiat-Sempe, Onkar Sharma, Christine Valfridsson, Lena Meyer, John F Love, Maghnus O'Seaghdha, Michael R Wessels, Jenny J Persson
Group A Streptococcus (GAS) is a common human pathogen and the etiologic agent of a large number of diseases ranging from mild, self-limiting infections to invasive life-threatening conditions. Two prominent virulence factors of this bacterium are the genetically and functionally linked pore-forming toxin streptolysin O (SLO) and its cotoxin NAD(+)-glycohydrolase (NADase). Overexpression of these toxins has been linked to increased bacterial virulence and is correlated with invasive GAS disease. NADase can be translocated into host cells by a SLO-dependent mechanism, and cytosolic NADase has been assigned multiple properties such as protection of intracellularly located GAS bacteria and induction of host cell death through energy depletion...
July 18, 2017: MBio
https://www.readbyqxmd.com/read/28719017/contrasting-sirtuin-and-parp-activity-of-selected-2-4-6-trisubstituted-benzimidazoles
#20
Keng Yoon Yeong, Soo Choon Tan, Chun-Wai Mai, Chee-Onn Leong, Felicia Fei-Lei Chung, Yean Kee Lee, Chin Fei Chee, Noorsaadah Abdul Rahman
Both sirtuin and poly(ADP-ribose)polymerase (PARP) family of enzymes utilize NAD+ as co-substrate. Inhibitors of sirtuins and PARPs are important tools in drug discovery as they are reported to be linked to multiple diseases such as cancer. New potent sirtuin inhibitors (2,4,6-trisubstituted benzimidazole) were discovered from reported PARP inhibitor scaffold. Interestingly, the synthesized compounds have contrasting sirtuin and PARP-1 inhibitory activity. We showed that modification on benzimidazoles may alter their selectivity towards sirtuin or PARP-1 enzymes...
July 18, 2017: Chemical Biology & Drug Design
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