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NAD+ increase AND Nicotinamide

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https://www.readbyqxmd.com/read/28724806/nicotinamide-mononucleotide-requires-sirt3-to-improve-cardiac-function-and-bioenergetics-in-a-friedreich-s-ataxia-cardiomyopathy-model
#1
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/28714034/inhibition-of-nampt-decreases-cell-growth-and-enhances-susceptibility-to-oxidative-stress
#2
Renhua Xu, Zhenwei Yuan, Lijuan Yang, Lele Li, Dan Li, Changjun Lv
Nicotinamide adenine dinucleotide (NAD) is an essential molecule for living organisms and plays a vital role in aging and age-associated diseases. In eukaryotic cells, cellular NAD is mainly generated by the scavenge pathway in which nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the formation of nicotinamide mononucleotide. Inhibition of NAMPT is a therapeutic strategy for cancer treatment. To explore the effects of NAMPT inhibition on cellular processes, cells were treated with 10 nM FK866, an NAMPT inhibitor, resulting in a decrease in the cellular NAD level, a lower growth rate, and enhanced susceptivity to oxidative stress as compared to the untreated cells...
July 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28714019/salidroside-protects-pc12-cells-from-a%C3%AE-1%C3%A2-40%C3%A2-induced-cytotoxicity-by-regulating-the-nicotinamide-phosphoribosyltransferase-signaling-pathway
#3
Xujiao Huang, Sanli Xing, Chuan Chen, Zhihua Yu, Jiulin Chen
Alzheimer's disease (AD) is the most common type of senile dementia, which often develops in elderly or presenile individuals. As one of the pathological features of AD, amyloid β‑protein (Aβ) causes energy dysmetabolism, thereby inducing cellular damage and apoptosis. Salidroside is the main active component of the traditional Chinese medicine Rhodiola. Previous studies have demonstrated that salidroside exerts a regulatory role in energy metabolism. However, the role and the mechanism of action of salidroside in AD remain unclear...
July 5, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28707004/host-sirtuin-1-regulates-mycobacterial-immunopathogenesis-and-represents-a-therapeutic-target-against-tuberculosis
#4
Catherine Y Cheng, Nuria M Gutierrez, Mardiana B Marzuki, Xiaohua Lu, Taylor W Foreman, Bhairav Paleja, Bernett Lee, Akhila Balachander, Jinmiao Chen, Liana Tsenova, Natalia Kurepina, Karen W W Teng, Kim West, Smriti Mehra, Francesca Zolezzi, Michael Poidinger, Barry Kreiswirth, Deepak Kaushal, Hardy Kornfeld, Evan W Newell, Amit Singhal
Mycobacterium tuberculosis (Mtb) executes a plethora of immune-evasive mechanisms, which contribute to its pathogenesis, limited efficacy of current therapy, and the emergence of drug-resistant strains. This has led to resurgence in attempts to develop new therapeutic strategies/targets against tuberculosis (TB). We show that Mtb down-regulates sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, in monocytes/macrophages, TB animal models, and TB patients with active disease...
March 2017: Science Immunology
https://www.readbyqxmd.com/read/28705804/loss-of-nitric-oxide-mediated-inhibition-of-purine-neurotransmitter-release-in-the-colon-in-the-absence-of-interstitial-cells-of-cajal
#5
Leonie Durnin, Andrea Lees, Sheerien Manzoor, Kent C Sasse, Kenton M Sanders, Violeta N Mutafova-Yambolieva
Regulation of colonic motility depends upon the integrity of enteric inhibitory neurotransmission mediated by nitric oxide (NO), purine neurotransmitters, and neuropeptides. Intramuscular interstitial cells of Cajal (ICC-IM) and platelet-derived growth factor receptor α-positive (PDGFRα(+)) cells are involved in generating responses to NO and purine neurotransmitters, respectively. Previous studies have suggested a decreased nitrergic and increased purinergic neurotransmission in Kit(W)/Kit(W-v) (W/W(v) ) mice that display lesions in ICC-IM along the gastrointestinal tract...
July 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28685427/imaging-redox-state-in-mouse-muscles-of-different-ages
#6
Lily Moon, David W Frederick, Joseph A Baur, Lin Z Li
Aging is the greatest risk factor for many diseases. Intracellular concentrations of nicotinamide adenine dinucleotide (NAD(+)) and the NAD(+)-coupled redox state have been proposed to moderate many aging-related processes, yet the specific mechanisms remain unclear. The concentration of NAD(+) falls with age in skeletal muscle, yet there is no consensus on whether aging will increase or decrease the redox potential of NAD(+)/NADH. Oxidized flavin groups (Fp) (e.g. FAD, i.e., flavin adenine dinucleotide, contained in flavoproteins) and NADH are intrinsic fluorescent indicators of oxidation and reduction status of tissue, respectively...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28677728/overexpression-of-sirt1-prevents-hypoxia%C3%A2-induced-apoptosis-in-osteoblast-cells
#7
Lu Zhou, Sung Il Wang, Young Jae Moon, Kyoung Min Kim, Kwang Bok Lee, Byung-Hyun Park, Kyu Yun Jang, Jung Ryul Kim
Hypoxic‑ischemic injury of the bone results in osteonecrosis. Nicotinamide adenosine dinucleotide (NAD)‑dependent deacetylase sirtuin‑1 (SIRT1), a type of NAD‑dependent deacetylase, is involved in multiple biological functions, particularly in anti‑apoptosis. However, the effects of SIRT1 in osteoblasts remain unclear and whether SIRT1 protects osteoblasts in hypoxic conditions remains to be elucidated. In the present study, the role of SIRT1 in the osteoblast cells under hypoxia and the underlying mechanism of the anti‑apoptotic activity of SIRT1 were investigated...
July 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28671679/2-deoxyadenosine-5-diphosphoribose-is-an-endogenous-trpm2-superagonist
#8
Ralf Fliegert, Andreas Bauche, Adriana-Michelle Wolf Pérez, Joanna M Watt, Monika D Rozewitz, Riekje Winzer, Mareike Janus, Feng Gu, Annette Rosche, Angelika Harneit, Marianne Flato, Christelle Moreau, Tanja Kirchberger, Valerie Wolters, Barry V L Potter, Andreas H Guse
Transient receptor potential melastatin 2 (TRPM2) is a ligand-gated Ca(2+)-permeable nonselective cation channel. Whereas physiological stimuli, such as chemotactic agents, evoke controlled Ca(2+) signals via TRPM2, pathophysiological stimuli such as reactive oxygen species and genotoxic stress result in prolonged TRPM2-mediated Ca(2+) entry and, consequently, apoptosis. To date, adenosine 5'-diphosphoribose (ADPR) has been assumed to be the main agonist for TRPM2. Here we show that 2'-deoxy-ADPR was a significantly better TRPM2 agonist, inducing 10...
June 26, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28668830/increased-nicotinamide-phosphoribosyltransferase-and-cystathionine-%C3%AE-synthase-in-renal-oncocytomas-renal-urothelial-carcinoma-and-renal-clear-cell-carcinoma
#9
Rodney E Shackelford, Jehan Abdulsattar, Eric X Wei, James Cotelingam, Domenico Coppola, Guillermo A Herrera
BACKGROUND: Renal oncocytomas (ROs), and clear cell (RCC) and urothelial carcinomas (UC), are common renal neoplasms. Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step of NAD(+) synthesis and its expression is increased in several tumors. Nampt concomitantly regulates hydrogen sulfide (H2S)-synthesizing enzyme levels, including cystathionine-β-synthase (CBS). MATERIALS AND METHODS: We used tissue microarrays to examine Nampt and the H2S-synthesizing enzyme CBS protein levels in benign kidney, RCC, UC and ROs...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28659716/aspects-of-tryptophan-and-nicotinamide-adenine-dinucleotide-in-immunity-a-new-twist-in-an-old-tale
#10
REVIEW
Hector Rodriguez Cetina Biefer, Anju Vasudevan, Abdallah Elkhal
Increasing evidence underscores the interesting ability of tryptophan to regulate immune responses. However, the exact mechanisms of tryptophan's immune regulation remain to be determined. Tryptophan catabolism via the kynurenine pathway is known to play an important role in tryptophan's involvement in immune responses. Interestingly, quinolinic acid, which is a neurotoxic catabolite of the kynurenine pathway, is the major pathway for the de novo synthesis of nicotinamide adenine dinucleotide (NAD+). Recent studies have shown that NAD+, a natural coenzyme found in all living cells, regulates immune responses and creates homeostasis via a novel signaling pathway...
2017: International Journal of Tryptophan Research: IJTR
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
#11
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/28642875/rapid-elimination-of-blood-alcohol-using-erythrocytes-mathematical-modeling-and-in-vitro-study
#12
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/28629697/increase-in-furfural-tolerance-by-combinatorial-overexpression-of-nad-salvage-pathway-enzymes-in-engineered-isobutanol-producing-e-coli
#13
Hun-Suk Song, Jong-Min Jeon, Hyun-Joong Kim, Shashi Kant Bhatia, Ganesan Sathiyanarayanan, Junyoung Kim, Ju Won Hong, Yoon Gi Hong, Kwon Young Choi, Yun-Gon Kim, Wooseong Kim, Yung-Hun Yang
To reduce the furfural toxicity for biochemical production in E. coli, a new strategy was successfully applied by supplying NAD(P)H through the nicotine amide salvage pathway. To alleviate the toxicity, nicotinamide salvage pathway genes were overexpressed in recombinant, isobutanol-producing E. coli. Gene expression of pncB and nadE respectively showed increased tolerance to furfural among these pathways. The combined expression of pncB and nadE was the most effective in increasing the tolerance of the cells to toxic aldehydes...
June 1, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28622864/isolation-and-characterization-of-avibacterium-paragallinarum-with-different-nicotinamide-adenine-dinucleotide-requirements
#14
Ok-Mi Jeong, Min-Su Kang, Byung-Woo Jeon, Byung-Kook Choi, Yong-Kuk Kwon, So-Youn Yoon, Patrick J Blackall, Hee-Soo Lee, Suk-Chan Jung, Jae-Hong Kim
Twenty field isolates of Avibacterium paragallinarum were obtained from chickens in South Korea during 2011-2015. The isolates were identified by a HPG-2 PCR assay specific for A. paragallinarum and by biochemical tests. Growth requirements, Page serovars, carbohydrate fermentation patterns, and antimicrobial susceptibility were also examined. Most isolates (16/20) showed the typical requirement for nicotinamide adenine dinucleotide (NAD) and an enriched CO2 atmosphere for growth. One isolate needed increased levels of NAD and serum for good growth...
June 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28621682/melatonin-inhibits-sirt1-dependent-nampt-and-nfat5-signaling-in-chondrocytes-to-attenuate-osteoarthritis
#15
Jia Yi Guo, Feng Li, Yong Bing Wen, Hong Xun Cui, Ma Long Guo, Lin Zhang, Yun Fei Zhang, Yan Jin Guo, Yan Xing Guo
Osteoarthritis (OA) is a degenerative joint disease mainly characterized by cartilage degradation. Interleukin-1β (IL-1β) contributes to OA pathogenesis by enhancing oxidative stress and inflammation. Melatonin reportedly elicits potent protection against OA. However, the role of melatonin and underlying mechanism in IL-1β-stimulated chondrocytes remain largely unclear. In this study, we found that melatonin inhibited IL-1β-induced toxicity and sirtuin 1 (Sirt1) enhancement in human chondrocytes. Melatonin reduced the IL-1β-increased nicotinamide phosphoribosyltransferase (NAMPT) expression and the NAD+ level in chondrocytes in a Sirt1-dependent manner...
June 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28604662/upregulation-of-mitochondrial-nad-levels-impairs-the-clonogenicity-of-ssea1-glioblastoma-tumor-initiating-cells
#16
Myung Jin Son, Jae-Sung Ryu, Jae Yun Kim, Youjeong Kwon, Kyung-Sook Chung, Seon Ju Mun, Yee Sook Cho
Emerging evidence has emphasized the importance of cancer therapies targeting an abnormal metabolic state of tumor-initiating cells (TICs) in which they retain stem cell-like phenotypes and nicotinamide adenine dinucleotide (NAD(+)) metabolism. However, the functional role of NAD(+) metabolism in regulating the characteristics of TICs is not known. In this study, we provide evidence that the mitochondrial NAD(+) levels affect the characteristics of glioma-driven SSEA1(+) TICs, including clonogenic growth potential...
June 9, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28592850/nad-augmentation-ameliorates-acute-pancreatitis-through-regulation-of-inflammasome-signalling
#17
AiHua Shen, Hyung-Jin Kim, Gi-Su Oh, Su-Bin Lee, Seung Hoon Lee, Arpana Pandit, Dipendra Khadka, Seong-Kyu Choe, Sung Chul Kwak, Sei-Hoon Yang, Eun-Young Cho, Hyun-Seok Kim, Hail Kim, Raekil Park, Tae Hwan Kwak, Hong-Seob So
Acute pancreatitis (AP) is a complicated disease without specific drug therapy. The cofactor nicotinamide adenine dinucleotide (NAD(+)) is an important regulator of cellular metabolism and homeostasis. However, it remains unclear whether modulation of NAD(+) levels has an impact on caerulein-induced AP. Therefore, in this study, we investigated the effect of increased cellular NAD(+) levels on caerulein-induced AP. We demonstrated for the first time that the activities and expression of SIRT1 were suppressed by reduction of intracellular NAD(+) levels and the p53-microRNA-34a pathway in caerulein-induced AP...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28591759/ppar%C3%AE-coactivator-1%C3%AE-nicotinamide-adenine-dinucleotide-and-renal-stress-resistance
#18
Ali Poyan Mehr, Samir M Parikh
With one of the highest mitochondrial densities in the body, the kidneys consume approximately 10% of total oxygen while constituting 0.5% of body mass. Renal respiration is linear to solute extraction, linking oxidative metabolism directly to tubular function. This fundamental role of mitochondria in renal health may become an "Achilles heel" under duress. Acute kidney injury (AKI) related to each major class of stressor - inflammation, ischemia, and toxins - exhibits early and prominent mitochondrial injury...
June 8, 2017: Nephron
https://www.readbyqxmd.com/read/28548540/nicotinamide-adenine-dinucleotide-metabolism-and-neurodegeneration
#19
Mariana Pehar, Benjamin A Harlan, Kelby M Killoy, Marcelo R Vargas
SIGNIFICANCE: Nicotinamide adenine dinucleotide (NAD(+)) participates in redox reactions and NAD(+)-dependent signaling processes, which involve the cleavage of NAD(+) coupled to posttranslational modifications of proteins or the production of second messengers. Either as a primary cause or as a secondary component of the pathogenic process, mitochondrial dysfunction and oxidative stress are prominent features of several neurodegenerative diseases. Activation of NAD(+)-dependent signaling pathways has a major effect in the capacity of the cell to modulate mitochondrial function and counteract the deleterious effects of increased oxidative stress...
June 27, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28546856/epigenetic-regulation-of-runx2-transcription-and-osteoblast-differentiation-by-nicotinamide-phosphoribosyltransferase
#20
Min Ling, Peixin Huang, Shamima Islam, Daniel P Heruth, Xuanan Li, Li Qin Zhang, Ding-You Li, Zhaohui Hu, Shui Qing Ye
BACKGROUND: Bone degenerative disorders like osteoporosis may be initiated by age-related shifts in anabolic and catabolic responses that control bone homeostasis. Although there are studies suggesting that metabolic changes occur with stem cell differentiation, the molecular mechanisms governing energy metabolism and epigenetic modification are not understood fully. Here we reported the key role of nicotinamide phosphoribosyltransferase (Nampt), which is the rate-limiting enzyme in the salvage pathway of NAD biosynthesis from nicotinamide, in the osteogenic differentiation of bone marrow stromal cells...
2017: Cell & Bioscience
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