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AMPK AND NAD+

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https://www.readbyqxmd.com/read/27913299/the-inhibitory-effect-of-beta-lapachone-on-rankl-induced-osteoclastogenesis
#1
Dong Ryun Gu, Joon No Lee, Gi-Su Oh, Hyung Jin Kim, Min Seuk Kim, Seoung Hoon Lee
β-lapachone (β-L) is a substrate of reduced nicotinamide adenine dinucleotide (NADH): quinone oxidoreductase 1 (NQO1). NQO1 reduces quinones to hydroquinones using NADH as an electron donor and consequently increases the intracellular NAD+/NADH ratio. The activation of NQO1 by β-L has beneficial effects on several metabolic syndromes, such as obesity, hypertension, and renal injury. However, the effect of β-L on bone metabolism remains unclear. Here, we show that β-L might be a potent inhibitor of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27824080/lycium-barbarum-polysaccharide-attenuates-high-fat-diet-induced-hepatic-steatosis-by-up-regulating-sirt1-expression-and-deacetylase-activity
#2
Li Jia, Wang Li, Jianning Li, Yan Li, Hui Song, Yansong Luan, Hui Qi, Lirong Ma, Xiaohong Lu, Yi Yang
In this study, we aimed to investigate the protective effects and underlying mechanism of Lycium barbarum polysaccharide (LBP) on high-fat-induced nonalcoholic fatty liver disease (NAFLD). Recently, sirtuin 1 (SIRT1) has been shown to play an important role in the regulation of hepatocellular lipid metabolism. Here, we demonstrated that LBP up-regulates SIRT1 deacetylase activity and protein expression by enhancing the NAD(+)/NADH ratio. Subsequently, LBP promoted LKB1 deacetylation and AMPK phosphorylation via SIRT1-dependent signalling...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27793977/acute-stimulation-of-glucose-influx-upon-mitoenergetic-dysfunction-requires-lkb1-ampk-sirt2-and-mtor-raptor
#3
Dania C Liemburg-Apers, Jori A L Wagenaars, Jan A M Smeitink, Peter H G M Willems, Werner J H Koopman
Mitochondria play a central role in cellular energy production, and their dysfunction can trigger a compensatory increase in glycolytic flux to sustain cellular ATP levels. Here, we studied the mechanism of this homeostatic phenomenon in C2C12 myoblasts. Acute (30 min) mitoenergetic dysfunction induced by the mitochondrial inhibitors piericidin A and antimycin A stimulated Glut1-mediated glucose uptake without altering Glut1 (also known as SLC2A1) mRNA or plasma membrane levels. The serine/threonine liver kinase B1 (LKB1; also known as STK11) and AMP-activated protein kinase (AMPK) played a central role in this stimulation...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27760313/a-mathematical-model-of-the-liver-circadian-clock-linking-feeding-and-fasting-cycles-to-clock-function
#4
Aurore Woller, Hélène Duez, Bart Staels, Marc Lefranc
To maintain energy homeostasis despite variable energy supply and consumption along the diurnal cycle, the liver relies on a circadian clock synchronized to food timing. Perturbed feeding and fasting cycles have been associated with clock disruption and metabolic diseases; however, the mechanisms are unclear. To address this question, we have constructed a mathematical model of the mammalian circadian clock, incorporating the metabolic sensors SIRT1 and AMPK. The clock response to various temporal patterns of AMPK activation was simulated numerically, mimicking the effects of a normal diet, fasting, and a high-fat diet...
October 18, 2016: Cell Reports
https://www.readbyqxmd.com/read/27737527/lonchocarpine-increases-nrf2-are-mediated-antioxidant-enzyme-expression-by-modulating-ampk-and-mapk-signaling-in-brain-astrocytes
#5
Yeon-Hui Jeong, Jin-Sun Park, Dong-Hyun Kim, Hee-Sun Kim
Lonchocarpine is a phenylpropanoid compound isolated from Abrus precatorius that has anti-bacterial, anti-inflammatory, antiproliferative, and antiepileptic activities. In the present study, we investigated the antioxidant effects of lonchocarpine in brain glial cells and analyzed its molecular mechanisms. We found that lonchocarpine suppressed reactive oxygen species (ROS) production and cell death in hydrogen peroxide-treated primary astrocytes. In addition, lonchocarpine increased the expression of antioxidant enzymes, such as heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), and manganese superoxide dismutase (MnSOD), which are all under the control of Nrf2/antioxidant response element (ARE) signaling...
November 1, 2016: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/27711204/metabolic-response-to-nad-depletion-across-cell-lines-is-highly-variable
#6
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
https://www.readbyqxmd.com/read/27613156/mesenchymal-stem-cells-conditioned-media-ameliorates-diabetic-endothelial%C3%A2-dysfunction%C3%A2-by-improving-mitochondrial-bioenergetics-via-the-sirt1-ampk-pgc-1%C3%AE-pathway
#7
Yujia Yuan, Meimei Shi, Lan Li, Jingping Liu, Bo Chen, Younan Chen, Xingxing An, Shuyun Liu, Ruixi Luo, Dan Long, Wengeng Zhang, Philip Newsholme, Jingqiu Cheng, Yanrong Lu
Vasculopathy is a major complication of diabetes. Impaired mitochondrial bioenergetics and biogenesis due to oxidative stress is a critical causal factor for diabetic endothelial dysfunction. Sirt1, a NAD(+)-dependent enzyme, is known to play an important protective role through deacetylation of many substrates involved in oxidative phosphorylation and reactive oxygen species (ROS) generation. Conditioned medium from mesenchymal stem cells (MSCs-CM) has emerged as a promising cell-free therapy due to the trophic actions of MSCs secreted molecules...
September 9, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27554679/carbon-monoxide-potentiation-of-l-type-ca2-channel-activity-increases-hif-1%C3%AE-independent-vegf-expression-via-an-ampk%C3%AE-sirt1-mediated-pgc-1%C3%AE-err%C3%AE-axis
#8
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
https://www.readbyqxmd.com/read/27519885/sirt6-overexpression-improves-various-aspects-of-mouse-healthspan
#9
Asael Roichman, Yariv Kanfi, Renana Glazz, Shoshana Naiman, Uri Amit, Natalie Landa, Simon Tinman, Ilan Stein, Eli Pikarsky, Jonathan Leor, Haim Y Cohen
The extension in human lifespan in the last century results in a significant increase in incidence of age related diseases. It is therefore crucial to identify key factors that control elderly healthspan. Similar to dietary restriction, mice overexpressing the NAD(+) dependent protein deacylase SIRT6 (MOSES) live longer and have reduced IGF-1 levels. However, it is as yet unknown whether SIRT6 also affects various healthspan parameters. Here, a range of age related phenotypes was evaluated in MOSES mice. In comparison to their wild-type (WT) littermates, old MOSES mice showed amelioration of a variety of age-related disorders, including: improved glucose tolerance, younger hormonal profile, reduced age-related adipose inflammation and increased physical activity...
August 12, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/27500459/treatment-with-nad-inhibited-experimental-autoimmune-encephalomyelitis-by-activating-ampk-sirt1-signaling-pathway-and-modulating-th1-th17-immune-responses-in-mice
#10
Jueqiong Wang, Congying Zhao, Peng Kong, Huanhuan Sun, Zhe Sun, Guanyun Bian, Yafei Sun, Li Guo
Nicotinamide adenine dinucleotide (NAD(+)) plays vital roles in mitochondrial functions, cellular energy metabolism and calcium homeostasis. In this study, we investigated the effect of NAD(+) administration for the treatment of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. EAE, a classical animal model of multiple sclerosis (MS), was induced by subcutaneous injection of myelin oligodendrocyteglycoprotein (MOG). The mice were treated with 250mg/kg (body weight) NAD(+) in PBS administered intraperitoneally once daily...
October 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27456392/activation-of-the-ampk-sirt1-pathway-by-a-leucine-metformin-combination-increases-insulin-sensitivity-in-skeletal-muscle-and-stimulates-glucose-and-lipid-metabolism-and-increases-life-span-in-caenorhabditis-elegans
#11
Jheelam Banerjee, Antje Bruckbauer, Michael B Zemel
BACKGROUND: We have previously shown leucine (Leu) to activate Sirt1 by lowering its KM for NAD(+), thereby amplifying the effects of other sirtuin activators and improving insulin sensitivity. Metformin (Met) converges on this pathway both indirectly (via AMPK) and by direct activation of Sirt1, and we recently found Leu to synergize with Met to improve insulin sensitivity and glycemic control while achieving ~80% dose-reduction in diet-induced obese mice. Accordingly, we sought here to define the mechanism of this interaction...
November 2016: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/27451147/slc25a22-promotes-proliferation-and-survival-of-colorectal-cancer-cells-with-kras-mutations-and-xenograft-tumor-progression-in-mice-via-intracellular-synthesis-of-aspartate
#12
Chi Chun Wong, Yun Qian, Xiaona Li, Jiaying Xu, Wei Kang, Joanna H Tong, Ka-Fai To, Ye Jin, Weilin Li, Huarong Chen, Minnie Yy Go, Jian-Lin Wu, Ka Wing Cheng, Simon Sm Ng, Joseph Jy Sung, Zongwei Cai, Jun Yu
BACKGROUND & AIMS: Many colorectal cancer (CRC) cells contain mutations in KRAS. Analyses of colorectal cancer cells with mutations in APC or CTNNB1 and KRAS identified SLC25A22, which encodes mitochondrial glutamate transporter, as a synthetic lethal gene. We investigated the functions of SLC25A22 in colorectal cancer cells with mutations in KRAS. METHODS: We measured levels of SLC25A22 mRNA and protein in paired tumor and nontumor colon tissues collected from 130 patients in Hong Kong and 17 patients in China, and compared protein levels with patient survival times...
July 20, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27417135/effects-of-the-nrf2-protein-modulator-salvianolic-acid-a-alone-or-combined-with-metformin-on-diabetes-associated-macrovascular-and-renal-injury
#13
Ping Wu, Yu Yan, Lin-Lin Ma, Bi-Yu Hou, Yang-Yang He, Li Zhang, Zi-Ran Niu, Jun-Ke Song, Xiao-Cong Pang, Xiu-Ying Yang, Guan-Hua Du
Nuclear factor E2-related factor 2 (Nrf2) is considered a promising target against diabetic complications such as cardiovascular diseases and diabetic nephropathy. Herein, we investigated the effects of a potential Nrf2 modulator, salvianolic acid A (SAA), which is a natural polyphenol, on diabetes-associated macrovascular and renal injuries in streptozotocin-induced diabetic mice. Given that lowering glucose is the first objective of diabetic patients, we also examined the effects of SAA combined with metformin (MET) on both complications...
October 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27393564/independent-amp-and-nad-signaling-regulates-c2c12-differentiation-and-metabolic-adaptation
#14
Chia George Hsu, Thomas J Burkholder
The balance of ATP production and consumption is reflected in adenosine monophosphate (AMP) and nicotinamide adenine dinucleotide (NAD) content and has been associated with phenotypic plasticity in striated muscle. Some studies have suggested that AMPK-dependent plasticity may be an indirect consequence of increased NAD synthesis and SIRT1 activity. The primary goal of this study was to assess the interaction of AMP- and NAD-dependent signaling in adaptation of C2C12 myotubes. Changes in myotube developmental and metabolic gene expression were compared following incubation with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and nicotinamide mononucleotide (NMN) to activate AMPK- and NAD-related signaling...
December 2016: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/27382348/resveratrol-attenuates-lipopolysaccharide-induced-dysfunction-of-blood-brain-barrier-in-endothelial-cells-via-ampk-activation
#15
Min Hu, Bo Liu
Resveratrol, a phytoalexin, is reported to activate AMP-activated protein kinase (AMPK) in vascular cells. The blood-brain barrier (BBB), formed by specialized brain endothelial cells that are interconnected by tight junctions, strictly regulates paracellular permeability to maintain an optimal extracellular environment for brain homeostasis. The aim of this study was to elucidate the effects of resveratrol and the role of AMPK in BBB dysfunction induced by lipopolysaccharide (LPS). Exposure of human brain microvascular endothelial cells (HBMECs) to LPS (1 µg/ml) for 4 to 24 hours week dramatically increased the permeability of the BBB in parallel with lowered expression levels of occluding and claudin-5, which are essential to maintain tight junctions in HBMECs...
July 2016: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/27374086/exogenous-pyruvate-facilitates-cancer-cell-adaptation-to-hypoxia-by-serving-as-an-oxygen-surrogate
#16
Chengqian Yin, Dan He, Shuyang Chen, Xiaoling Tan, Nianli Sang
Molecular oxygen is the final electron acceptor in cellular metabolism but cancer cells often become adaptive to hypoxia, which promotes resistance to chemotherapy and radiation. The reduction of endogenous glycolytic pyruvate to lactate is known as an adaptive strategy for hypoxic cells. Whether exogenous pyruvate is required for hypoxic cell proliferation by either serving as an electron acceptor or a biosynthetic substrate remains unclear. By using both hypoxic and ρ0 cells defective in electron transfer chain, we show that exogenous pyruvate is required to sustain proliferation of both cancer and non-cancer cells that cannot utilize oxygen...
June 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27345396/o-glcnacylation-regulates-breast-cancer-metastasis-via-sirt1-modulation-of-foxm1-pathway
#17
C M Ferrer, T Y Lu, Z A Bacigalupa, C D Katsetos, D A Sinclair, M J Reginato
Tumors utilize aerobic glycolysis to support growth and invasion. However, the molecular mechanisms that link metabolism with invasion are not well understood. The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) modifies intracellular proteins with N-acetylglucosamine. Cancers display elevated O-GlcNAcylation and suppression of O-GlcNAcylation inhibits cancer invasion and metastasis. Here, we show that the regulation of cancer invasion by OGT is dependent on the NAD(+)-dependent deacetylase SIRT1...
June 27, 2016: Oncogene
https://www.readbyqxmd.com/read/27343380/-s-ys-51-a-novel-isoquinoline-alkaloid-attenuates-obesity-associated-non-alcoholic-fatty-liver-disease-in-mice-by-suppressing-lipogenesis-inflammation-and-coagulation
#18
Eun Jung Park, Young Min Kim, Hye Jung Kim, Se-Yun Jang, Moo Hyun Oh, Duck-Hyung Lee, Ki Churl Chang
Obesity-associated non-alcoholic fatty liver disease (NAFLD) increases coagulation and inflammation. We hypothesized that (S)YS-51, an agent found to be beneficial in animal models of sepsis, may reduce NAFLD in high-fat diet (HFD) mice by reducing coagulation and inflammation. C57BL/6 mice were fed either a chow diet or HFD and each was supplemented with or without (S)YS-51 (10mg/kg, daily, i.p.) for 16 weeks. The results showed that HFD caused significant increases in lipogenesis [CD36, fatty acid synthase (FAS) and sterol response element binding protein (SREBP)-1c mRNA and protein], inflammation [monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-α, intercellular cell adhesion molecule-1 (ICAM-1), TGF-β, and procollagen type 1 mRNA, macrophage infiltration] and coagulation [tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) mRNA and thrombin antithrombin complex (TAT)] in the liver, adipose tissue and serum, which were significantly reduced by (S)YS-51...
October 5, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27313401/inhibition-of-extracellular-calcium-influx-results-in-enhanced-il-12-production-in-lps-treated-murine-macrophages-by-downregulation-of-the-camkk%C3%AE-ampk-sirt1-signaling-pathway
#19
Xin Liu, Ning Wang, Yuanfeng Zhu, Yongjun Yang, Xiaoli Chen, Shijun Fan, Qian Chen, Hong Zhou, Jiang Zheng
Activated macrophages are the primary sources of IL-12, a key cytokine bridging innate and adaptive immunity. However, macrophages produce low amounts of IL-12 upon stimulation and the underlying regulatory mechanism remains unclear. In this study, we found a new calcium-dependent mechanism that controlled IL-12 production in LPS-treated murine macrophages. First, LPS was demonstrated to induce extracellular calcium entry in murine peritoneal macrophages and inhibition of calcium influx resulted in marked enhancement in IL-12 production...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27260465/a-conjugated-fatty-acid-present-at-high-levels-in-bitter-melon-seed-favorably-affects-lipid-metabolism-in-hepatocytes-by-increasing-nad-nadh-ratio-and-activating-ppar%C3%AE-ampk-and-sirt1-signaling-pathway
#20
Gou-Chun Chen, Hui-Min Su, Yu-Shun Lin, Po-Yen Tsou, Jong-Ho Chyuan, Pei-Min Chao
α-Eleostearic acid (α-ESA), or the cis-9, trans-11, trans-13 isomer of conjugated linolenic acid, is a special fatty acid present at high levels in bitter melon seed oil. The aim of this study was to examine the effect of α-ESA on hepatic lipid metabolism. Using H4IIEC3 hepatoma cell line, we showed that α-ESA significantly lowered intracellular triglyceride accumulation compared to α-linolenic acid (LN), used as a fatty acid control, in a dose- and time-dependent manner. The effects of α-ESA on enzyme activities and mRNA profiles in H4IIEC3 cells suggested that enhanced fatty acid oxidation and lowered lipogenesis were involved in α-ESA-mediated triglyceride lowering effects...
July 2016: Journal of Nutritional Biochemistry
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