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AMP activated kinase

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https://www.readbyqxmd.com/read/28805975/antofine-suppresses-endotoxin-induced-inflammation-and-metabolic-disorder-via-amp-activated-protein-kinase
#1
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
#2
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
#3
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)...
July 21, 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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28791738/metformin-promotes-neuronal-differentiation-and-neurite-outgrowth-through-ampk-activation-in-human-bone-marrow-mesenchymal-stem-cells
#13
Min-Ji Ahn, Goang-Won Cho
Metformin is an AMP-activated kinase (AMPK) activator that plays a role in glucose energy metabolism and cell protection. It is widely used to treat several diseases, including type 2 diabetes, cardiovascular diseases, cancer, and metabolic diseases. In this study, we investigated whether AMPK activation upon treatment with metformin may promote neurite outgrowth during the progression of neuronal differentiation in human bone marrow-mesenchymal stem cells (hBM-MSCs). Differentiation of metformin-treated MSCs (Met-MSCs to Met-diMSCs) in the neuronal induction media resulted in an increase in the number of differentiated cells in a metformin concentration-dependent manner...
August 9, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28791004/the-camp-pka-signaling-pathway-regulates-pathogenicity-hyphal-growth-appressorial-formation-conidiation-and-stress-tolerance-in-colletotrichum-higginsianum
#14
Wenjun Zhu, Man Zhou, Zeyang Xiong, Fang Peng, Wei Wei
Colletotrichum higginsianum is an economically important pathogen that causes anthracnose disease in a wide range of cruciferous crops. Understanding the mechanisms of the cruciferous plant-C. higginsianum interactions will be important in facilitating efficient control of anthracnose diseases. The cAMP-PKA signaling pathway plays important roles in diverse physiological processes of multiple pathogens. C. higginsianum contains two genes, ChPKA1 and ChPKA2, that encode the catalytic subunits of cyclic AMP (cAMP)-dependent protein kinase A (PKA)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28783244/loss-of-ampk-activation-promotes-the-invasion-and-metastasis-of-pancreatic-cancer-through-an-hsf1-dependent-pathway
#15
Ke Chen, Weikun Qian, Jie Li, Zhengdong Jiang, Liang Cheng, Bin Yan, Junyu Cao, Liankang Sun, Cancan Zhou, Meng Lei, Wanxing Duan, Jiguang Ma, Qingyong Ma, Zhenhua Ma
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a mortality rate that closely parallels its incidence rate, and a better understanding of the molecular and cellular mechanisms associated with the invasion and distant metastasis is required. Heat shock factor 1 (HSF1) is a very highly conserved factor in eukaryotes that regulates the protective heat shock response. Here, we show that HSF1 is abnormally activated in pancreatic cancer. The knockdown of HSF1 impaired the invasion and migration and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells in vitro; however, the up-regulation of HSF1 showed the opposite effects...
August 7, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28782252/cyclic-amp-dependent-post-translational-modification-of-neuronal-nitric-oxide-synthase-neuroprotects-penile-erection-in-rats
#16
Serkan Karakus, Biljana Musicki, Justin D La Favor, Arthur L Burnett
OBJECTIVES: To evaluate nNOS phosphorylation, nNOS uncoupling, and oxidative stress in the penis and major pelvic ganglia (MPG), before and after the administration of the cAMP-dependent protein kinase A (PKA) agonist colforsin in a rat model of bilateral cavernous nerve injury (BCNI) which mimics nerve injury following prostatectomy. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were divided into BCNI and sham groups. Each group included 2 subgroups: vehicle and colforsin (0...
August 7, 2017: BJU International
https://www.readbyqxmd.com/read/28776086/the-mechanisms-of-action-of-metformin
#17
REVIEW
Graham Rena, D Grahame Hardie, Ewan R Pearson
Metformin is a widely-used drug that results in clear benefits in relation to glucose metabolism and diabetes-related complications. The mechanisms underlying these benefits are complex and still not fully understood. Physiologically, metformin has been shown to reduce hepatic glucose production, yet not all of its effects can be explained by this mechanism and there is increasing evidence of a key role for the gut. At the molecular level the findings vary depending on the doses of metformin used and duration of treatment, with clear differences between acute and chronic administration...
August 3, 2017: Diabetologia
https://www.readbyqxmd.com/read/28768770/nmda-receptors-mediate-leptin-signaling-and-regulate-potassium-channel-trafficking-in-pancreatic-%C3%AE-cells
#18
Yi Wu, Dale A Fortin, Veronica A Cochrane, Pei-Chun Chen, Show-Ling Shyng
NMDA receptors (NMDARs) are Ca2+-permeant, ligand-gated ion channels activated by the excitatory neurotransmitter glutamate and have well-characterized roles in the nervous system. The expression and function of NMDARs in pancreatic β cells, by contrast, are poorly understood. Here, we report a novel function of NMDARs in β-cells. Using a combination of biochemistry, electrophysiology, and imaging techniques we now show that NMDARs have a key role in mediating the effect of leptin to modulate β-cell electrical activity by promoting AMP-activated protein kinase (AMPK)-dependent trafficking of KATP and Kv2...
August 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28768660/regulation-of-energy-metabolism-during-social-interactions-in-rainbow-trout-a-role-for-amp-activated-protein-kinase
#19
Kathleen M Gilmour, Paul M Craig, Rashpal S Dhillon, Gigi Y Lau, Jeffrey G Richards
Rainbow trout (Oncorhynchus mykiss) confined in pairs form social hierarchies in which subordinate fish typically experience fasting and high circulating cortisol levels, resulting in low growth rates. The present study investigated the role of AMP-activated protein kinase (AMPK) in mediating metabolic adjustments associated with social status in rainbow trout. After 3 d of social interaction, liver AMPK activity in subordinate trout was significantly higher than that of dominant or sham (fish handled in the same fashion as paired fish but held individually) trout...
August 2, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28768281/%C3%AE-sarcoglycan-deficiency-reduces-atherosclerotic-plaque-development-in-apoe-null-mice
#20
Vignesh Murugesan, Eva Degerman, Ann-Kristin Holmen-Pålbrink, Pontus Duner, Anki Knutsson, Anna Hultgårdh-Nilsson, Uwe Rauch
BACKGROUND: Smooth muscle cells are important for atherosclerotic plaque stability. Their proper ability to communicate with the extracellular matrix is crucial for maintaining the correct tissue integrity. In this study, we have investigated the role of β-sarcoglycan within the matrix-binding dystrophin-glycoprotein complex in the development of atherosclerosis. RESULTS: Atherosclerotic plaque development was significantly reduced in ApoE-deficient mice lacking β-sarcoglycan, and their plaques contained an increase in differentiated smooth muscle cells...
July 29, 2017: Journal of Vascular Research
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