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Delphine Ohayon, Alessia De Chiara, Nicolas Chapuis, Céline Candalh, Julie Mocek, Jean-Antoine Ribeil, Lamya Haddaoui, Norbert Ifrah, Olivier Hermine, Frédéric Bouillaud, Philippe Frachet, Didier Bouscary, Véronique Witko-Sarsat
Cytosolic proliferating cell nuclear antigen (PCNA), a scaffolding protein involved in DNA replication, has been described as a key element in survival of mature neutrophil granulocytes, which are non-proliferating cells. Herein, we demonstrated an active export of PCNA involved in cell survival and chemotherapy resistance. Notably, daunorubicin-resistant HL-60 cells (HL-60R) have a prominent cytosolic PCNA localization due to increased nuclear export compared to daunorubicin-sensitive HL-60 cells (HL-60S)...
October 19, 2016: Scientific Reports
Jan Hansen, Silvie Timmers, Esther Moonen-Kornips, Helene Duez, Bart Staels, Matthijs K C Hesselink, Patrick Schrauwen
Cell and animal studies have demonstrated that circadian rhythm is governed by autonomous rhythmicity of clock genes. Although disturbances in circadian rhythm have been implicated in metabolic disease development, it remains unknown whether muscle circadian rhythm is altered in human models of type 2 diabetes. Here we used human primary myotubes (HPM) to investigate if rhythmicity of clock- and metabolic gene expression is altered in donors with obesity or type 2 diabetes compared to metabolically healthy donors...
October 19, 2016: Scientific Reports
Ivyna Bong Pau Ni, Ng Ching Ching, Shaik Kamal Fakiruddin, Lim Moon Nian, Zubaidah Zakaria
Multiple myeloma (MM) is a malignancy of B lymphocytes or plasma cells. Our array-based comparative genomic hybridization findings revealed chromosomal gains at 7q22.3 and 1q42.3, where nicotinamide (NAM) phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) genes are localized, respectively. This led us to further study the functions of these genes in myeloma cells. NAMPT is a key enzyme involved in nicotinamide adenine dinucleotide salvage pathway, and it is frequently overexpressed in human cancers...
October 18, 2016: Bosnian Journal of Basic Medical Sciences
Hirokazu Muraoka, Kazuhiro Hasegawa, Shu Wakino
OBJECTIVE: Nicotinamide phosphoribosyltransferase (Nampt) cooperates with a longevity gene, Sirt1, to exert the potentiation of stress resistance. We have reported that the high expression level of Nampt in PTs contributes to the sufficient supply of NMN to glomeruli. We also showed that downregulation of Nampt and NMN in PT in DN leads to glomerular damages (Nature Medicine 2013). However, the regulation mechanisms of Nampt expression remain unknown. DESIGN AND METHOD: We investigated how Nampt expression is consistently retained at high levels in PTs under normal conditions and how Nampt levels are decreased in DN...
September 2016: Journal of Hypertension
Charlotte Ridler
No abstract text is available yet for this article.
October 14, 2016: Nature Reviews. Endocrinology
Reiko Sanokawa-Akakura, Shin Akakura, Siamak Tabibzadeh
Recent evidence suggests that hydrogen sulfide (H2S) has cytoprotective and anti-aging effects. However, the mechanisms for such properties are not fully understood. Here, we show that the expression of the main H2S producing enzyme, CBS, and production of H2S are coordinately diminished in replicative senescent adult human dermal fibroblasts. The reduced production of H2S falls within the same time-frame that the hallmarks of replicative senescence appear including accumulation of SA-β-Gal, enhanced expression of p16, p21, and RRM2B while the expression of RRM2, hTERT, SIRT1, NAMPT, and NAD/NADH ratio all fall...
2016: PloS One
Aleksander J Owczarek, Magdalena Olszanecka-Glinianowicz, Piotr Kocełak, Maria Bożentowicz-Wikarek, Aniceta Brzozowska, Małgorzata Mossakowska, Monika Puzianowska-Kuźnicka, Tomasz Grodzicki, Andrzej Więcek, Jerzy Chudek
BACKGROUND: The available literature suggests that circulating visfatin/Nicotinamide Phosphoribosyltransferase (NAMPT) level variability in humans is related to obesity, insulin resistance, inflammation, and lipid profile. The aim of the study was to assess the relationship between circulating visfatin/NAMPT, obesity, insulin resistance, inflammation, and lipid profile in a large population-based, elderly cohort, applying structural equation modeling. MATERIALS AND METHODS: The analysis included 2983 elderly participants of the PolSenior study with assessed total blood count, fasting concentrations of lipids, glucose, insulin, hs-CRP, interleukin-6, and visfatin/NAMPT (by ELISA), and calculated HOMA-IR...
October 7, 2016: Scandinavian Journal of Clinical and Laboratory Investigation
Yang Xiao, Mandy Kwong, Anneleen Daemen, Marcia Belvin, Xiaorong Liang, Georgia Hatzivassiliou, Thomas O'Brien
Nicotinamide adenine dinucleotide (NAD) is a cofactor involved in a wide range of cellular metabolic processes and is a key metabolite required for tumor growth. NAMPT, nicotinamide phosphoribosyltransferase, which converts nicotinamide (NAM) to nicotinamide mononucleotide (NMN), the immediate precursor of NAD, is an attractive therapeutic target as inhibition of NAMPT reduces cellular NAD levels and inhibits tumor growth in vivo. However, there is limited understanding of the metabolic response to NAD depletion across cancer cell lines and whether all cell lines respond in a uniform manner...
2016: PloS One
Anna-Karin Elf, Peter Bernhardt, Tobias Hofving, Yvonne Arvidsson, Eva Forssell-Aronsson, Bo Wängberg, Ola Nilsson, Viktor Johanson
: Neuroendocrine tumors (NETs) can be treated by peptide receptor radionuclide therapy using radiolabeled somatostatin analogs. However, the efficacy of such treatment is low and needs to be optimized. AIMS: To evaluate the potential radiosensitizing effects of NAMPT inhibition on (177)Lu-DOTATATE treatment in a NET model. METHODS: Nude mice xenografted with the human NET cell line GOT1 were treated with semi-efficient doses of (177)Lu-DOTATATE (7,5 MBq, i...
September 29, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Bin Xiang, Lichi Han, Xinyue Wang, Ling Tang, Kailiang Li, Xiuxiu Li, Xibo Zhao, Miaomiao Xia, Xixi Zhou, Fuyin Zhang, Ke Jian Liu
PURPOSE: Radiation therapy for head and neck cancer commonly leads to radiation sialadenitis. Emerging evidence has indicated that phenylephrine pretreatment reduces radiosensitivity in the salivary gland; however, the underlying cytoprotective mechanism remains unclear. Nicotinamide phosphoribosyltransferase (NAMPT) is not only a key enzyme for the nicotinamide adenine dinucleotide salvage pathway, but also a cytokine participating in cell survival, metabolism, and longevity, with a broad effect on cellular functions in physiology and pathology...
November 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Jonathan B Lin, Shunsuke Kubota, Norimitsu Ban, Mitsukuni Yoshida, Andrea Santeford, Abdoulaye Sene, Rei Nakamura, Nicole Zapata, Miyuki Kubota, Kazuo Tsubota, Jun Yoshino, Shin-Ichiro Imai, Rajendra S Apte
Photoreceptor death is the endpoint of many blinding diseases. Identifying unifying pathogenic mechanisms in these diseases may offer global approaches for facilitating photoreceptor survival. We found that rod or cone photoreceptor-specific deletion of nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in the major NAD(+) biosynthetic pathway beginning with nicotinamide, caused retinal degeneration. In both cases, we could rescue vision with nicotinamide mononucleotide (NMN). Significantly, retinal NAD(+) deficiency was an early feature of multiple mouse models of retinal dysfunction, including light-induced degeneration, streptozotocin-induced diabetic retinopathy, and age-associated dysfunction...
September 27, 2016: Cell Reports
Jose A Santiago, Alyssa M Littlefield, Judith A Potashkin
Emerging research indicates that depression could be one of the earliest prodromal symptoms or risk factors associated with the pathogenesis of Parkinson's disease (PD), the second most common neurodegenerative disorder worldwide, but the mechanisms underlying the association between both diseases remains unknown. Understanding the molecular networks linking these diseases could facilitate the discovery of novel diagnostic and therapeutics. Transcriptomic meta-analysis and network analysis of blood microarrays from untreated patients with PD and depression identified genes enriched in pathways related to the immune system, metabolism of lipids, glucose, fatty acids, nicotinamide, lysosome, insulin signaling and type 1 diabetes...
September 29, 2016: Scientific Reports
Hirokazu Muraoka, Kazuhiro Hasegawa, Shu Wakino
OBJECTIVE: Nicotinamide phosphoribosyltransferase (Nampt) cooperates with a longevity gene, Sirt1, to exert the potentiation of stress resistance. We have reported that the high expression level of Nampt in PTs contributes to the sufficient supply of NMN to glomeruli. We also showed that downregulation of Nampt and NMN in PT in DN leads to glomerular damages (Nature Medicine 2013). However, the regulation mechanisms of Nampt expression remain unknown. DESIGN AND METHOD: We investigated how Nampt expression is consistently retained at high levels in PTs under normal conditions and how Nampt levels are decreased in DN...
September 2016: Journal of Hypertension
Hui-Ying Liu, Qing-Ran Li, Xue-Fang Cheng, Guang-Ji Wang, Hai-Ping Hao
Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the first rate-limiting step in converting nicotinamide to NAD(+), essential for a number of enzymes and regulatory proteins involved in a variety of cellular processes, including deacetylation enzyme SIRT1 which modulates several tumor suppressors such as p53 and FOXO. Herein we report that NQO1 substrates Tanshione IIA (TSA) and β-lapachone (β-lap) induced a rapid depletion of NAD(+) pool but adaptively a significant upregulation of NAMPT. NAMPT inhibition by FK866 at a nontoxic dose significantly enhanced NQO1-targeting agent-induced apoptotic cell death...
August 2016: Chinese Journal of Natural Medicines
Clara Herrera-Arozamena, Olaia Martí-Marí, Martín Estrada, Mario de la Fuente Revenga, María Isabel Rodríguez-Franco
The central nervous system of adult mammals has long been considered as a complex static structure unable to undergo any regenerative process to refurbish its dead nodes. This dogma was challenged by Altman in the 1960s and neuron self-renewal has been demonstrated ever since in many species, including humans. Aging, neurodegenerative, and some mental diseases are associated with an exponential decrease in brain neurogenesis. Therefore, the controlled pharmacological stimulation of the endogenous neural stem cells (NSCs) niches might counteract the neuronal loss in Alzheimer's disease (AD) and other pathologies, opening an exciting new therapeutic avenue...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Xiaowan Wang, Hailong Li, Shinghua Ding
We previously demonstrated that Pre-B-cell colony-enhancing factor (PBEF), also known as nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD(+) biosynthesis pathway, plays a brain and neuronal protective role in ischemic stroke. In this study, we further investigated the mechanism of its neuroprotective effect after ischemia in the primary cultured mouse cortical neurons. Using apoptotic cell death assay, fluorescent imaging, molecular biology, mitochondrial biogenesis measurements and Western blotting analysis, our results show that the overexpression of PBEF in neurons can significantly promote neuronal survival, reduce the translocation of apoptosis inducing factor (AIF) from mitochondria to nuclei and inhibit the activation of capase-3 after glutamate-induced excitotoxicity...
2016: Scientific Reports
Guang-Feng Ming, Kai Wu, Kai Hu, Yao Chen, Jian Xiao
The importance of endothelial progenitor cells (EPCs) in cardiovascular diseases has been demonstrated by numerous studies. Previous studies have shown that Nicotinamide phosphoribosyltransferase (NAMPT) plays a role in EPC development by regulating Sirtuin 1 (SIRT1), but the specific mechanism has not yet been elucidated. After stimulating EPCs with NAMPT, expression of SIRT1 and SIRT1 antisense long non-coding RNA (AS lncRNA) was upregulated. Upon transfection of an SIRT1 AS lncRNA overexpression vector into EPCs, SIRT1 expression was upregulated...
September 23, 2016: Biochemical and Biophysical Research Communications
S Riammer, A Garten, M Schaab, S Grunewald, W Kiess, J Kratzsch, U Paasch
High amounts of nicotinamide phosphoribosyltransferase (NAMPT) were found in human seminal plasma. This enzyme influences energy metabolism and apoptosis and is essential for the regulation of cellular nicotinamide adenine dinucleotide (NAD)(+) levels in somatic cells. NAD(+) is required as a co-substrate for dehydrogenases, which are potentially important for spermatogenesis. The functional significance of intra- and extracellular NAMPT in human reproduction, however, has not been defined yet. The objectives of the study were therefore to determine NAMPT protein expression in human spermatozoa and testes, the secretion of NAMPT by spermatozoa depending on their maturation stage and the impact of NAMPT enzymatic function on sperm viability, motility, fertilisation capacity and induction of apoptosis...
August 27, 2016: Andrology
Yoon Kyung Choi, Ji-Hee Kim, Dong-Keon Lee, Kwang-Soon Lee, Moo-Ho Won, Dooil Jeoung, Hansoo Lee, Kwon-Soo Ha, Young-Guen Kwon, Young-Myeong Kim
AIMS: The heme oxygenase-1 (HO-1)/carbon monoxide (CO) pathway induced in astrocytes after ischemic brain injury promotes vascular endothelial growth factor (VEGF) expression to maintain and repair neurovascular function. Although HO-1-derived CO has been shown to induce hypoxia-inducible factor-1α (HIF-1α)-dependent VEGF expression, the underlying mechanism independent of HIF-1α remains to be elucidated. RESULTS: HO-1 and VEGF were co-expressed in astrocytes of ischemic mouse brain tissues...
August 23, 2016: Antioxidants & Redox Signaling
Larisa Diana Mocan Hognogi, Luminita Vida Simiti
As it had been already stated by latest research, inflammation is a condition which sits at the very base of atherogenesis, which is the major consequence of the metabolic syndrome. It was stated that adipose tissue impacts all organs by the synthesis of adipokines. Visfatin/NAMPT is a biomarker that was recently discovered in mice (2005). In the beginning it was believed to have insulin-like properties, but afterwards research has found important links between Visfatin and inflammation, endothelial dysfunction and atherosclerosis in coronary artery disease...
2016: Clujul Medical (1957)
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