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AMP-activated protein kinase

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https://www.readbyqxmd.com/read/28820290/local-histone-acetylation-by-acss2-promotes-gene-transcription-for-lysosomal-biogenesis-and-autophagy
#1
Xinjian Li, Xu Qian, Zhimin Lu
Overcoming metabolic stress is a critical step in tumorigenesis. Acetyl coenzyme A (acetyl-CoA) converted from glucose or acetate is a substrate used for histone acetylation to regulate gene expression. However, how acetyl-CoA is produced under nutritional stress conditions is unclear. Herein we report that nutritional stress induces nuclear translocation of ACSS2 (acyl-CoA synthetase short-chain family member 2). This translocation is mediated by AMP-activated protein kinase (AMPK)-dependent ACSS2 Ser659 phosphorylation and subsequent exposure of the nuclear localization signal of ACSS2 to KPNA1/importin α5 for binding...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28819881/resveratrol-induces-apoptosis-and-inhibits-adipogenesis-by-stimulating-the-sirt1-ampk%C3%AE-foxo1-signalling-pathway-in-bovine-intramuscular-adipocytes
#2
Xiaomu Liu, Hongbo Zhao, Qing Jin, Wei You, Haijian Cheng, Yifan Liu, Enliang Song, Guifen Liu, Xiuwen Tan, Xianglun Zhang, Fachun Wan
Sirtuin type 1 (SIRTl) and AMP-activated protein kinase (AMPK) play important roles in regulating energy metabolism, cell proliferation and differentiation, ageing, apoptosis, and metabolism. The effect of 100, 200, and 400 μm Resveratrol (RES), an activator of SIRT1, on apoptosis of bovine intramuscular adipocytes was investigated by nuclear staining, flow cytometry, quantitative real-time polymerase chain reaction, and western blotting. Results show that RES inhibited adipogenesis, decreased cell viability, and increased apoptotic rates in a dose-dependent way...
August 17, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28816632/the-liver-circadian-clock-modulates-biochemical-and-physiological-responses-to-metformin
#3
Emma Henriksson, Anne-Laure Huber, Erin K Soto, Anna Kriebs, Megan E Vaughan, Drew Duglan, Alanna B Chan, Stephanie J Papp, Madelena Nguyen, Megan E Afetian, Katja A Lamia
Metformin is widely used in the treatment of type 2 diabetes to lower blood glucose. Although metformin is a relatively safe and effective drug, its clinical efficacy is variable and under certain circumstances it may contribute to life-threatening lactic acidosis. Thus, additional understanding of metformin pharmacokinetics and pharmacodynamics could provide important information regarding therapeutic use of this widely prescribed drug. Here we report a significant effect of time of day on acute blood glucose reduction in response to metformin administration and on blood lactate levels in healthy mice...
August 2017: Journal of Biological Rhythms
https://www.readbyqxmd.com/read/28813521/correction-liver-amp-activated-protein-kinase-is-unnecessary-for-gluconeogenesis-but-protects-energy-state-during-nutrient-deprivation
#4
Clinton M Hasenour, Martha L Wall, D Emerson Ridley, Freyja D James, Curtis C Hughey, E Patrick Donahue, Benoit Viollet, Marc Foretz, Jamey D Young, David H Wasserman
[This corrects the article DOI: 10.1371/journal.pone.0170382.].
2017: PloS One
https://www.readbyqxmd.com/read/28811293/the-glucagon-like-peptide-1-receptor-in-the-ventromedial-hypothalamus-reduces-short-term-food-intake-in-male-mice-by-regulating-nutrient-sensor-activity
#5
Melissa A Burmeister, Jacob D Brown, Jennifer E Ayala, Doris A Stoffers, Darleen A Sandoval, Randy J Seeley, Julio E Ayala
Pharmacological activation of the glucagon-like peptide 1 receptor (GLP-1R) in the ventromedial hypothalamus (VMH) reduces food intake. Here, we assessed whether suppression of food intake by GLP-1R agonists (GLP-1RA) in this region is dependent upon AMP-activated protein kinase (AMPK) and mammalian Target of Rapamycin (mTOR). We found that pharmacological inhibition of glycolysis and, thus, activation of AMPK, in the VMH attenuates the anorectic effect of the GLP-1R agonist exendin-4 (Ex4), indicating that glucose metabolism and inhibition of AMPK are both required for this effect...
August 15, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28810598/differentially-methylated-regions-in-patients-with-rheumatic-heart-disease-and-secondary-pulmonary-arterial-hypertension
#6
Dawei Zheng, Xiaoying Chen, Ni Li, Lebo Sun, Qingyun Zhou, Huoshun Shi, Guodong Xu, Jing Liu, Limin Xu, Shiwei Duan, Guofeng Shao
The aim of the present study was to identify differentially methylated regions (DMRs) in patients with rheumatic heart disease and secondary pulmonary arterial hypertension (RHD-PAH). A genome-wide DNA methylation assay was performed between 6 patients with RHD-PAH and 6 healthy controls using an Illumina Infinium HumanMethylation450 BeadChip kit. The Limma software package was subsequently used to identify significant DMRs. A total of 40 hypome-thylated and 64 hypermethylated CpG sites were identified between the RHD-PAH group and the control group...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28807827/the-endotoxemia-cardiac-dysfunction-is-attenuated-by-ampk-mtor-signaling-pathway-regulating-autophagy
#7
Jie Zhang, Peng Zhao, Nanhu Quan, Lin Wang, Xu Chen, Courtney Cates, Thomas Rousselle, Ji Li
AMP-activated protein kinase (AMPK), an enzyme that plays a role in cellular energy homeostasis, modulates myocardial signaling in the heart. Myocardial dysfunction is a common complication of sepsis. Autophagy is involved in the aging related cardiac dysfunction. However, the role of AMPK in sepsis-induced cardiotoxicity has yet to be clarified, especially in aging. In this study, we explored the role of AMPK on lipopolysaccharide (LPS)-induced myocardial dysfunction and elucidated the potential mechanisms of AMPK/mTOR pathway against autophagy in young and aged mice...
August 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28807345/ampk-expression-patterns-are-significantly-associated-with-poor-prognosis-in-breast-cancer-patients
#8
Jaudah Al-Maghrabi, Kaltoom Al-Sakkaf, Imtiaz Ahmad Qureshi, Nadeem Shafique Butt, Lila Damnhory, Mohamed Elshal, Basim Al-Maghrabi, Alia Aldahlawi, Sawsan Ashoor, Barry Brown, Pauline Dobson, Mohamad Nidal Khabaz
Many investigators have examined the functions of AMP-activated protein kinase (AMPK) in cancer biology and its anti-neoplastic features in cancer models. The goal of this research is to assess the association of the immunohistochemical expression of AMPK in human mammary tumours with the clinical data of breast cancer patients. 449 cases of previously diagnosed breast cancer, and 27 tissue samples of fibroadenomas and normal breast were utilized for detection of AMPK expression using tissue microarrays and immunohistochemistry...
August 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28805975/antofine-suppresses-endotoxin-induced-inflammation-and-metabolic-disorder-via-amp-activated-protein-kinase
#9
Shao-Ting Chou, Fang Jung, Shih-Hsing Yang, Hwei-Ling Chou, Guey-Mei Jow, Jau-Chen Lin
The inhibition of activated macrophages has been used to develop anti-inflammatory agents for therapeutic intervention to human diseases that cause excessive inflammatory responses. Antofine, a phenanthroindolizidine alkaloid, has a potent anti-inflammatory effect. However, the molecular mechanisms of its anti-inflammatory activity have not yet been fully detailed. In this study, we comprehensively explored the anti-inflammatory effects of antofine on endotoxin-induced inflammation in macrophages using cDNA microarray analysis, thereby elucidating the potential mechanism by which antofine suppresses inflammation...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28805903/chronic-activation-of-amp-activated-protein-kinase-increases-monocarboxylate-transporter-2-and-4-expression-in-skeletal-muscle
#10
E M England, H Shi, S K Matarneh, E M Oliver, E T Helm, T L Scheffler, E Puolanne, D E Gerrard
Acute activation of AMP-activated protein kinase (AMPK) increases monocarboxylate transporter (MCT) expression in skeletal muscle. However, the impact of chronic activation of AMPK on MCT expression in skeletal muscle is unknown. To investigate, MCT1, MCT2, and MCT4 mRNA expression and protein abundance were measured in the longissimus lumborum (glycolytic), masseter (oxidative), and heart from wild-type (control) and AMPK γ3 pigs. The AMPK γ3 gain in function mutation results in AMPK being constitutively active in glycolytic skeletal muscle and increases energy producing pathways...
August 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28803777/paraoxonase-2-facilitates-pancreatic-cancer-growth-and-metastasis-by-stimulating-glut1-mediated-glucose-transport
#11
Arvindhan Nagarajan, Shaillay Kumar Dogra, Lisha Sun, Neeru Gandotra, Thuy Ho, Guoping Cai, Gary Cline, Priti Kumar, Robert A Cowles, Narendra Wajapeyee
Metabolic deregulation is a hallmark of human cancers, and the glycolytic and glutamine metabolism pathways were shown to be deregulated in pancreatic ductal adenocarcinoma (PDAC). To identify new metabolic regulators of PDAC tumor growth and metastasis, we systematically knocked down metabolic genes that were overexpressed in human PDAC tumor samples using short hairpin RNAs. We found that p53 transcriptionally represses paraoxonase 2 (PON2), which regulates GLUT1-mediated glucose transport via stomatin. The loss of PON2 initiates the cellular starvation response and activates AMP-activated protein kinase (AMPK)...
August 17, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28803158/balasubramide-derivative-3c-modulates-microglia-activation-via-camkk%C3%AE-dependent-ampk-pgc-1%C3%AE-pathway-in-neuroinflammatory-conditions
#12
Yunjie Wang, Wenchen Ruan, Junru Mi, Jingzi Xu, Haojie Wang, Zhengyu Cao, Juan M Saavedra, Luyong Zhang, Hansen Lin, Tao Pang
Neuroinflammation plays a vital role in the pathological process of cerebral ischemic stroke, but currently there is no effective treatment. After ischemia, microglia-produced proinflammatory mediator expression contributes to the aggravation of neuroinflammation, while anti-inflammatory activation of microglia develops an anti-neuroinflammatory effect via secretion of anti-inflammatory factor. Promoting the anti-inflammatory activation of microglia might be an effective treatment of stroke. Previously, we discovered one derivative of the natural product (+)-balasubramide, compound 3C, that exhibits a remarkably anti-neuroinflammatory effect in vitro with unknown mechanisms...
August 9, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28803067/ppargc1a-is-upregulated-and-facilitates-lung-cancer-metastasis
#13
Jin-Dong Li, Qing-Chuan Feng, Yu Qi, Guanghui Cui, Song Zhao
Lung cancer remains a leading cause of cancer-related mortality, with metastatic progression remaining the single largest cause of lung cancer mortality. Hence it is imperative to determine reliable biomarkers for lung cancer prognosis. We performed quantitative real-time PCR (qRT-PCR) analysis to explore epithelial-mesenchymal transition (EMT) inducers that regulate EMT process in three patients with advanced lung cancer disease. Peroxisome proliferator-activated receptor gamma (PPARGC1A) was uniformly the topmost overexpressed gene in all three human non-small cell lung cancer (NSCLC) patient samples...
August 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28802060/taurine-upregulated-gene-1-functions-as-a-master-regulator-to-coordinate-glycolysis-and-metastasis-in-hepatocellular-carcinoma
#14
Yang-Hsiang Lin, Meng-Han Wu, Ya-Hui Huang, Chau-Ting Yeh, Mei-Ling Cheng, Hsiang-Cheng Chi, Chung-Ying Tsai, I-Hsiao Chung, Ching-Ying Chen, Kwang-Huei Lin
Cancer cells display altered glucose metabolism characterized by a preference for aerobic glycolysis. The aerobic glycolytic phenotype of hepatocellular carcinoma (HCC) is often correlated with tumor progression and poorer clinical outcomes. However, the issue of whether glycolytic metabolism influences metastasis in HCC remains unclear. In the current study, we showed that knockdown of Taurine upregulated gene 1 (TUG1) induces marked inhibition of cell migration, invasion and glycolysis via suppression of miR-455-3p...
August 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28801758/prkag2-mutations-presenting-in-infancy
#15
Rachel D Torok, Stephanie L Austin, Chanika Phornphutkul, Kathleen M Rotondo, Deeksha Bali, Gregory H Tatum, Stephanie B Wechsler, Anne F Buckley, Priya S Kishnani
PRKAG2 encodes the γ2 subunit of AMP-activated protein kinase (AMPK), which is an important regulator of cardiac metabolism. Mutations in PRKAG2 cause a cardiac syndrome comprising ventricular hypertrophy, pre-excitation, and progressive conduction-system disease, which is typically not diagnosed until adolescence or young adulthood. However, significant variability exists in the presentation and outcomes of patients with PRKAG2 mutations, with presentation in infancy being underrecognized. The diagnosis of PRKAG2 can be challenging in infants, and we describe our experience with three patients who were initially suspected to have Pompe disease yet ultimately diagnosed with mutations in PRKAG2...
August 11, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28800474/nps-2143-a-selective-calcium-sensing-receptor-antagonist-inhibits-lipopolysaccharide-induced-pulmonary-inflammation
#16
Jae-Won Lee, Hyun Ah Park, Ok-Kyoung Kwon, Ji-Won Park, Gilhye Lee, Hee Jae Lee, Seung Jin Lee, Sei-Ryang Oh, Kyung-Seop Ahn
NPS 2143, a novel and selective antagonist of calcium-sensing receptor (CaSR) has been reported to possess anti-inflammatory activity. In the present study, we examined the protective effect of NPS 2143 on lipopolysaccharide (LPS)-induced acute lung injury (ALI). NPS 2143 pretreatment significantly inhibited the influx of inflammatory cells and the expression of monocyte chemoattractant protein-1 (MCP-1) in the lung of mice with LPS-induced ALI. NPS 2143 decreased the levels of neutrophil elastase (NE) and protein concentration in the bronchoalveolar lavage fluid (BALF)...
August 8, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28799785/anthocyanins-anthocyanidins-and-colorectal-cancer-what-is-behind-the-scenes
#17
Luís Fernando de Sousa Moraes, Xiaofei Sun, Maria do Carmo Gouveia Peluzio, Mei-Jun Zhu
Colorectal cancer (CRC) is one of the most common cause of cancer death. Phytochemicals, especially anthocyanins/anthocyanidins (A/A), have gathered attention of the scientific community owing to its anti-inflammatory, antioxidant, and cancer-inhibitory properties. In this review, we discussed the possible mechanisms whereby A/A exhibit intestinal anticarcinogenic characteristics. Anthocyanins/anthocyanidins inhibit the pro-inflammatory NF-κB pathway, attenuate Wnt signaling and suppress abnormal epithelial cell proliferation...
August 11, 2017: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/28799249/opposing-effects-on-cardiac-function-by-calorie-restriction-in-different-aged-mice
#18
Yunlu Sheng, Shan Lv, Min Huang, Yifan Lv, Jing Yu, Juan Liu, Tingting Tang, Hanmei Qi, Wenjuan Di, Guoxian Ding
Calorie restriction (CR) increases average and maximum lifespan and exhibits an apparent beneficial impact on age-related diseases. Several studies have shown that CR initiated either in middle or old age could improve ischemic tolerance and rejuvenate the aging heart; however, the data are not uniform when initiated in young. The accurate time to initiate CR providing maximum benefits for cardiac remodeling and function during aging remains unclear. Thus, whether a similar degree of CR initiated in mice of different ages could exert a similar effect on myocardial protection was investigated in this study...
August 11, 2017: Aging Cell
https://www.readbyqxmd.com/read/28799229/sitagliptin-mediated-preservation-of-endothelial-progenitor-cell-function-via-augmenting-autophagy-enhances-ischaemic-angiogenesis-in-diabetes
#19
Xiaozhen Dai, Jun Zeng, Xiaoqing Yan, Qian Lin, Kai Wang, Jing Chen, Feixia Shen, Xuemei Gu, Yuehui Wang, Jun Chen, Kejian Pan, Lu Cai, Kupper A Wintergerst, Yi Tan
Recently, the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin, a major anti-hyperglycaemic agent, has received substantial attention as a therapeutic target for cardiovascular diseases via enhancing the number of circulating endothelial progenitor cells (EPCs). However, the direct effects of sitagliptin on EPC function remain elusive. In this study, we evaluated the proangiogenic effects of sitagliptin on a diabetic hind limb ischaemia (HLI) model in vivo and on EPC culture in vitro. Treatment of db/db mice with sitagliptin (Januvia) after HLI surgery efficiently enhanced ischaemic angiogenesis and blood perfusion, which was accompanied by significant increases in circulating EPC numbers...
August 10, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28793265/a-hepatic-gabp-ampk-axis-links-inflammatory-signaling-to-systemic-vascular-damage
#20
Katharina Niopek, Bilgen Ekim Üstünel, Susanne Seitz, Minako Sakurai, Annika Zota, Frits Mattijssen, Xiaoyue Wang, Tjeerd Sijmonsma, Yvonne Feuchter, Anna M Gail, Barbara Leuchs, Dominik Niopek, Oskar Staufer, Maik Brune, Carsten Sticht, Norbert Gretz, Karin Müller-Decker, Hans-Peter Hammes, Peter Nawroth, Thomas Fleming, Michael D Conkright, Matthias Blüher, Anja Zeigerer, Stephan Herzig, Mauricio Berriel Diaz
Increased pro-inflammatory signaling is a hallmark of metabolic dysfunction in obesity and diabetes. Although both inflammatory and energy substrate handling processes represent critical layers of metabolic control, their molecular integration sites remain largely unknown. Here, we identify the heterodimerization interface between the α and β subunits of transcription factor GA-binding protein (GAbp) as a negative target of tumor necrosis factor alpha (TNF-α) signaling. TNF-α prevented GAbpα and β complex formation via reactive oxygen species (ROS), leading to the non-energy-dependent transcriptional inactivation of AMP-activated kinase (AMPK) β1, which was identified as a direct hepatic GAbp target...
August 8, 2017: Cell Reports
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