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AMP activated kinase

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https://www.readbyqxmd.com/read/28335578/exploring-the-antitumor-mechanism-of-high-dose-cytarabine-through-the-metabolic-perturbations-of-ribonucleotide-and-deoxyribonucleotide-in-human-promyelocytic-leukemia-hl-60-cells
#1
Zheng Li, Jian-Ru Guo, Qian-Qian Chen, Cai-Yun Wang, Wei-Jia Zhang, Mei-Cun Yao, Wei Zhang
Despite the apparent clinical benefits of high-dose cytarabine (Ara-C) over lower dose Ara-C in acute myeloid leukemia (AML) therapy, the mechanism behind high-dose Ara-C therapy remains uncertain. In this study, a LC-MS-based method was carried out to investigate the metabolic alteration of ribonucleotide and deoxyribonucleotide in human promyelocytic leukemia cells (HL-60) after treatment with Ara-C to reveal its antitumor mechanism. The metabolic results revealed that four nucleotides (ATP, ADP, CDP, and dCTP) could be used as potential biomarkers indicating the benefit of high-dose Ara-C over lower dose Ara-C treatment...
March 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28335379/the-role-of-adenosine-signaling-in-headache-a-review
#2
REVIEW
Nathan T Fried, Melanie B Elliott, Michael L Oshinsky
Migraine is the third most prevalent disease on the planet, yet our understanding of its mechanisms and pathophysiology is surprisingly incomplete. Recent studies have built upon decades of evidence that adenosine, a purine nucleoside that can act as a neuromodulator, is involved in pain transmission and sensitization. Clinical evidence and rodent studies have suggested that adenosine signaling also plays a critical role in migraine headache. This is further supported by the widespread use of caffeine, an adenosine receptor antagonist, in several headache treatments...
March 13, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28334808/downregulation-of-pathways-implicated-in-liver-inflammation-and-tumorigenesis-of-glycogen-storage-disease-type-ia-mice-receiving-gene-therapy
#3
Goo-Young Kim, Joon Hyun Kwon, Jun-Ho Cho, Lisa Zhang, Brian C Mansfield, Janice Y Chou
Glycogen storage disease type Ia (GSD-Ia) is characterized by impaired glucose homeostasis and long-term risks of hepatocellular adenoma (HCA) and carcinoma (HCC). We have shown that the non-tumor-bearing (NT), recombinant adeno-associated virus (rAAV) vector-treated GSD-Ia mice (AAV-NT mice) expressing a wide range (0.9-63%) of normal hepatic glucose-6-phosphatase-α activity maintain glucose homeostasis and display physiologic features mimicking animals living under calorie restriction (CR). We now show that in AAV-NT mice, the signaling pathways of the CR mediators, AMP-activated protein kinase (AMPK) and sirtuin-1 are activated...
March 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28332637/evaluation-of-the-immunomodulatory-activity-of-the-chicken-nk-lysin-derived-peptide-cnk-2
#4
Woo H Kim, Hyun S Lillehoj, Wongi Min
Chicken NK-lysin (cNK-lysin), the chicken homologue of human granulysin, is a cationic amphiphilic antimicrobial peptide (AMP) that is produced by cytotoxic T cells and natural killer cells. We previously demonstrated that cNK-lysin and cNK-2, a synthetic peptide incorporating the core α-helical region of cNK-lysin, have antimicrobial activity against apicomplexan parasites such as Eimeria spp., via membrane disruption. In addition to the antimicrobial activity of AMPs, the immunomodulatory activity of AMPs mediated by their interactions with host cells is increasingly recognized...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331191/identification-of-a-novel-small-molecule-partial-agonist-for-the-cyclic-amp-sensor-epac1
#5
Euan Parnell, Stuart P McElroy, Jolanta Wiejak, Gemma L Baillie, Alison Porter, David R Adams, Holger Rehmann, Brian O Smith, Stephen J Yarwood
Screening of a carefully selected library of 5,195 small molecules identified 34 hit compounds that interact with the regulatory cyclic nucleotide-binding domain (CNB) of the cAMP sensor, EPAC1. Two of these hits (I942 and I178) were selected for their robust and reproducible inhibitory effects within the primary screening assay. Follow-up characterisation by ligand observed nuclear magnetic resonance (NMR) revealed direct interaction of I942 and I178 with EPAC1 and EPAC2-CNBs in vitro. Moreover, in vitro guanine nucleotide exchange factor (GEF) assays revealed that I942 and, to a lesser extent, I178 had partial agonist properties towards EPAC1, leading to activation of EPAC1, in the absence of cAMP, and inhibition of GEF activity in the presence of cAMP...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28330873/amp-activated-protein-kinase-%C3%AE-1-promotes-atherogenesis-by-increasing-monocyte-to-macrophage-differentiation
#6
Miao Zhang, Huaiping Zhu, Ye Ding, Zhaoyu Liu, Zhejun Cai, Ming-Hui Zou
Monocyte-to-macrophage differentiation, which can be initiated by physiological or atherogenic factors, is a pivotal process in atherogenesis, a disorder in which monocytes adhere to endothelial cells and subsequently migrate into the sub-endothelial spaces, where they differentiate into macrophages and macrophage-derived foam cells and cause atherosclerotic lesions. However, the monocyte-differentiation signaling pathways that are activated by atherogenic factors are poorly defined. Here we report that the AMP- activated protein kinase (AMPK) α1 in monocytes promotes atherosclerosis by increasing monocyte differentiation and survival...
March 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28330809/piperine-attenuates-pathological-cardiac-fibrosis-via-ppar-%C3%AE-akt-pathways
#7
Zhen-Guo Ma, Yu-Pei Yuan, Xin Zhang, Si-Chi Xu, Sha-Sha Wang, Qi-Zhu Tang
Mitogen-activated protein kinases (MAPKs) and AMP-activated protein kinase α (AMPKα) play critical roles in the process of cardiac hypertrophy. Previous studies have demonstrated that piperine activates AMPKα and reduces the phosphorylation of extracellular signal-regulated kinase (ERK). However, the effect of piperine on cardiac hypertrophy remains completely unknown. Here, we show that piperine-treated mice had similar hypertrophic responses as mice treated with vehicle but exhibited significantly attenuated cardiac fibrosis after pressure overload or isoprenaline (ISO) injection...
March 14, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28327709/fish-oil-supplementation-inhibits-endoplasmic-reticulum-stress-and-improves-insulin-resistance-involvement-of-amp-activated-protein-kinase
#8
Wenqi Yang, Xu Chen, Ming Chen, Yanping Li, Qing Li, Xinwei Jiang, Yan Yang, Wenhua Ling
The beneficial effects of fish oil consumption on glucose metabolism have been generally reported. However, the mechanism underlying the fish oil-induced protective effects against insulin resistance remains unclear. Endoplasmic reticulum (ER) stress is recognized as an important contributor to insulin resistance. The aim of this study is to evaluate whether fish oil supplementation reduces ER stress and ameliorates insulin resistance in diet-induced obese mice, and to investigate the molecular mechanism of fish oil-induced benefits on ER stress...
March 22, 2017: Food & Function
https://www.readbyqxmd.com/read/28325731/effects-of-genetic-deletion-of-soluble-5-nucleotidases-nt5c1a-and-nt5c2-on-ampk-activation-and-nucleotide-levels-in-contracting-mouse-skeletal-muscles
#9
Samanta Kviklyte, Didier Vertommen, Xavier Yerna, Harriet Andersén, Xiufeng Xu, Philippe Gailly, Mohammad Bohlooly-Y, Jan Oscarsson, Mark H Rider
AMP-activated protein kinase (AMPK) plays a key role in energy homeostasis and is activated in response to contraction-induced ATP depletion in skeletal muscle via a rise in intracellular AMP/ADP concentrations. AMP can be deaminated by AMP-deaminase to IMP, which is hydrolysed to inosine by cytosolic 5'-nucleotidase-II (NT5C2). AMP can also be hydrolysed to adenosine by cytosolic 5'-nucleotidase-IA (NT5C1A). Previous gene silencing and overexpression studies indicated control of AMPK activation by NT5C enzymes...
March 21, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323520/anti-proliferation-effect-of-guanosine-on-hct-116-cells-involves-mapk-and-ampk-pathways
#10
Wuen Yew Teoh, Norhanom Abdul Wahab, Kae Shin Sim
This study aims to investigate the mechanisms associated with the anti-proliferation effect of guanosine on human colon carcinoma HCT 116 cells. In this study, guanosine induced more drastic cell cycle arrest effect than cell death effect on HCT 116 cells. The cell cycle arrest effect of guanosine on HCT 116 cells appeared to be associated with the increased activation of mitogen-activated protein kinases (MAPK) such as ERK1/2, p38 and JNK. The decreased of AMP-activated protein kinase (AMPK) activation and cyclin D1 expression was also involved...
March 21, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28323211/metabolic-pathway-of-4-pyridone-3-carboxamide-1%C3%AE-d-ribonucleoside-and-its-effects-on-cellular-energetics
#11
Iwona Pelikant-Malecka, Ewa Kaniewska-Bednarczuk, Sylwia Szrok, Alicja Sielicka, Maciej Śledziński, Czesława Orlewska, Ryszard T Smolenski, Ewa M Słomińska
4-Pirydone-3-carboxamide-1β-D-ribonucleoside (4PYR) is an endogenous nucleoside that could be converted to triphosphates, diphosphates, monophosphates and an analogue of NAD - 4PYRAD. Elevated level of these compounds were observed in chronic renal failure, cancer and active HIV infection. However, little is known about the effect on cell functionality and the metabolic pathways. This study tested effects of 4PYR in different cell types on nucleotide and energy metabolism and clarified enzymes that are involved in conversions of 4PYR...
March 17, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28322508/the-influence-of-ampk-subunit-alpha-2-prkaa2-genetic-polymorphisms-with-susceptibility-with-type-2-diabetes-mellitus-and-diabetic-nephropathy-in-chinese-population
#12
Qingchu Li, Cuilin Li, Haoyun Li, Liu Zeng, Zhiqiang Kang, Yu Mao, Xinyue Tang, Panpan Zheng, Li He, Fang Luo, Zhi Li
BACKGROUND: It has been well recognized that the AMP-activated protein kinase (AMPK) is a key factor influencing the development of type 2 diabetes mellitus (T2DM). The single-nucleotide polymorphism (SNP) rs2746342 in AMPK α2 subunit gene (PRKAA2) has been found to be associated with the susceptibility to T2DM in the Chinese Han population recently. This study further investigates the association of PRKAA2 genotypes with the susceptibility to T2DM and its complication disease, diabetic nephropathy...
March 21, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/28321180/multiple-kinases-involved-in-the-nicotinic-modulation-of-gamma-oscillations-in-the-rat-hippocampal-ca3-area
#13
JianGang Wang, XiaoLong He, Fangli Guo, XiangLin Cheng, Yali Wang, XiaoFang Wang, ZhiWei Feng, Martin Vreugdenhil, ChengBiao Lu
Neuronal synchronization at gamma band frequency (20-80 Hz, γ oscillations) is closely associated with higher brain function, such as learning, memory and attention. Nicotinic acetylcholine receptors (nAChRs) are highly expressed in the hippocampus, and modulate hippocampal γ oscillations, but the intracellular mechanism underlying such modulation remains elusive. We explored multiple kinases by which nicotine can modulate γ oscillations induced by kainate in rat hippocampal area CA3 in vitro. We found that inhibitors of cyclic AMP dependent kinase (protein kinase A, PKA), protein kinase C (PKC), N-methyl-D-aspartate receptor (NMDA) receptors, Phosphoinositide 3-kinase (PI3K) and extracellular signal-related kinases (ERK), each individually could prevent the γ oscillation-enhancing effect of 1 μM nicotine, whereas none of them affected baseline γ oscillation strength...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28320596/phillyrin-lowers-body-weight-in-obese-mice-via-the-modulation-of-ppar-beta-delta-angptl-4-pathway
#14
Hong-Bo Xiao, Guo-Guang Sui, Xiang-Yang Lu
OBJECTIVE: Previous investigations have shown that the peroxisome proliferator activated receptor beta/delta (PPAR<beta>/<delta>)-angiopoietin-like protein 4 (ANGPTL4) pathways may be a new pharmacologic target for treatment of obesity. The present study was conducted to test the effect of phillyrin, ‎a glucoside, on obesity in mice. METHOD: Fifty mice were randomly divided into 5 groups (n=10): control group (C57BL/6J mice), obese mice group, two groups of obese mice treated with phillyrin (15 or 45mg/kg/day), one group of obese mice treated with PPAR<beta>/<delta> agonist GW0742 (3mg/kg/day)...
March 17, 2017: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/28319830/anti-proliferative-effect-of-metformin-on-a-feline-injection-site-sarcoma-cell-line-independent-of-mtor-inhibition
#15
J Pierro, C Saba, K McLean, R Williams, E Karpuzoglu, R Prater, K Hoover, R Gogal
Metformin is an oral hypoglycemic drug that has been shown to inhibit cancer cell proliferation via up-regulation of AMPK (AMP-activated protein kinase), and possibly inhibition of mTOR (mammalian target of rapamycin). The purpose of this study was to evaluate the effects of metformin on a feline injection site sarcoma cell line. Cells from a feline injection site sarcoma cell line were treated with metformin at varied concentrations. A dose-dependent decrease in cell viability following metformin treatment was observed, with an IC50 of 8...
March 6, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28319810/inhibitors-of-glut-slc2a-enhance-the-action-of-bcnu-and-temozolomide-against-high-grade-gliomas
#16
Alberto Azzalin, Giulia Nato, Elena Parmigiani, Francesca Garello, Annalisa Buffo, Lorenzo Magrassi
Glucose transport across glioblastoma membranes plays a crucial role in maintaining the enhanced glycolysis typical of high-grade gliomas and glioblastoma. We tested the ability of two inhibitors of the glucose transporters GLUT/SLC2A superfamily, indinavir (IDV) and ritonavir (RTV), and of one inhibitor of the Na/glucose antiporter type 2 (SGLT2/SLC5A2) superfamily, phlorizin (PHZ), in decreasing glucose consumption and cell proliferation of human and murine glioblastoma cells. We found in vitro that RTV, active on at least three different GLUT/SLC2A transporters, was more effective than IDV, a specific inhibitor of GLUT4/SLC2A4, both in decreasing glucose consumption and lactate production and in inhibiting growth of U87MG and Hu197 human glioblastoma cell lines and primary cultures of human glioblastoma...
March 17, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28319060/the-anti-diabetic-drug-exenatide-a-glucagon-like-peptide-1-receptor-agonist-counteracts-hepatocarcinogenesis-through-camp-pka-egfr-stat3-axis
#17
M Zhou, M T S Mok, H Sun, A W Chan, Y Huang, A S L Cheng, G Xu
Epidemiological studies have demonstrated a close association of type 2 diabetes and hepatocellular carcinoma (HCC). Exenatide (Ex-4), a potent diabetes drug targeting glucagon-like peptide-1 receptor (GLP-1R), is protective against non-alcoholic fatty liver disease (NAFLD). However, the Ex-4 function and GLP-1R status have yet been explored in HCC. Herein we investigated the effect of Ex-4 in diethylnitrosamine (DEN)-treated mice consuming control or high-fat high-carbohydrate diet. Administration of Ex-4 significantly improved obesity-induced hyperglycemia and hyperlipidemia and reduced HCC multiplicity in obese DEN-treated mice, in which suppressed proliferation and induced apoptosis were confined to tumor cells...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28317895/upregulation-of-skeletal-muscle-pgc-1%C3%AE-through-the-elevation-of-cyclic-amp-levels-by-cyanidin-3-glucoside-enhances-exercise-performance
#18
Toshiya Matsukawa, Hideko Motojima, Yuki Sato, Shinya Takahashi, Myra O Villareal, Hiroko Isoda
Regular exercise and physical training enhance physiological capacity and improve metabolic diseases. Skeletal muscles require peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) in the process of their adaptation to exercise owing to PGC-1α's ability to regulate mitochondrial biogenesis, angiogenesis, and oxidative metabolism. Cyanidin-3-glucoside (Cy3G) is a natural polyphenol and a nutraceutical factor, which has several beneficial effects on human health. Here, the effect of Cy3G on exercise performance and the underlying mechanisms involved were investigated...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315774/molecular-characterization-of-amp-activated-protein-kinase-%C3%AE-2-from-herbivorous-fish-megalobrama-amblycephala-and-responsiveness-to-glucose-loading-and-dietary-carbohydrate-levels
#19
Chao Xu, Wen-Bin Liu, Ding-Dong Zhang, Kai-Zhou Wang, Si-Lei Xia, Xiang-Fei Li
This study aimed to characterize the full-length cDNA of AMPKα2 in Megalobrama amblycephala, and evaluate its potential role in glucose homeostasis and carbohydrate metabolism. The cDNA obtained covered 1942bp with an open reading frame of 1635bp encoding 545 amino acids. Multiple alignments and phylogenetic analysis revealed a high homology (91-100%) among most fish and higher vertebrates. This AMPKα2 mRNA predominantly expressed in muscle, liver and brain, while little in gill and intestine. Then, the AMPKα2 expressions were determined in the muscle, liver and brain of fish subjected to a glucose load (injected intraperitoneally with 0, 1...
March 16, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28315332/nuclear-ampk-regulated-carm1-stabilization-impacts-autophagy-in-aged-heart
#20
Chen Li, Lu Yu, Han Xue, Zheng Yang, Yue Yin, Bo Zhang, Mai Chen, Heng Ma
Senescence-associated autophagy downregulation leads to cardiomyocyte dysfunction. Coactivator-associated arginine methyltransferase 1 (CARM1) participates in many cellular processes, including autophagy in mammals. However, the effect of CARM1 in aging-related cardiac autophagy decline remains undefined. Moreover, AMP-activated protein kinase (AMPK) is a key regulator in metabolism and autophagy, however, the role of nuclear AMPK in autophagy outcome in aged hearts still unclear. Hers we identify the correlation between nuclear AMPK and CARM1 in aging heart...
March 15, 2017: Biochemical and Biophysical Research Communications
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