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AMP activated kinase

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https://www.readbyqxmd.com/read/29224101/estradiol-regulation-of-brown-adipose-tissue-thermogenesis
#1
Ismael González-García, Manuel Tena-Sempere, Miguel López
Physiologically, estrogens carry out a myriad of functions, the most essential being the regulation of the reproductive axis. Currently, it is also dogmatic that estrogens play an important role modulating energy balance and metabolism. In this sense, it is well known that low estrogens levels, occurring due to ovarian insufficiency, in conditions such as menopause or ovariectomy (OVX), are associated with increased food intake and decreased energy expenditure, leading to weight gain and obesity at long term...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29219657/the-levels-of-mutant-k-ras-and-mutant-n-ras-are-rapidly-reduced-in-a-beclin1-atg5-dependent-fashion-by-the-irreversible-erbb1-2-4-inhibitor-neratinib
#2
Laurence Booth, Jane L Roberts, Andrew Poklepovic, John Kirkwood, Cindy Sander, Francesca Avogadri-Connors, Richard E Cutler, Alshad S Lalani, Paul Dent
The FDA approved irreversible inhibitor of ERBB1/2/4, neratinib, was recently shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET and mutant K-RAS via autophagic degradation. In the present studies, in a dose-dependent fashion, neratinib reduced the expression levels of mutant K-RAS or of mutant N-RAS, which was augmented in an additive to greater than additive fashion by the HDAC inhibitors sodium valproate and AR42. Neratinib could reduce PDGFRα levels in GBM cells, that was enhanced by sodium valproate...
December 8, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29215013/allosteric-pyruvate-kinase-based-logic-gate-synergistically-senses-energy-and-sugar-levels-in-mycobacterium-tuberculosis
#3
Wenhe Zhong, Liang Cui, Boon Chong Goh, Qixu Cai, Peiying Ho, Yok Hian Chionh, Meng Yuan, Abbas El Sahili, Linda A Fothergill-Gilmore, Malcolm D Walkinshaw, Julien Lescar, Peter C Dedon
Pyruvate kinase (PYK) is an essential glycolytic enzyme that controls glycolytic flux and is critical for ATP production in all organisms, with tight regulation by multiple metabolites. Yet the allosteric mechanisms governing PYK activity in bacterial pathogens are poorly understood. Here we report biochemical, structural and metabolomic evidence that Mycobacterium tuberculosis (Mtb) PYK uses AMP and glucose-6-phosphate (G6P) as synergistic allosteric activators that function as a molecular "OR logic gate" to tightly regulate energy and glucose metabolism...
December 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/29214644/acute-oxygen-sensing-by-the-carotid-body-a-rattlebag-of-molecular-mechanisms
#4
Ryan J Rakoczy, Christopher N Wyatt
The molecular underpinnings of the oxygen-sensitivity of the carotid body Type I cells are becoming better defined as research begins to identify potential interactions between previously separate theories. Nevertheless, the field of oxygen-chemoreception still presents the general observer with a bewildering array of potential signalling pathways by which a fall in oxygen levels might initiate Type I cell activation. The purpose of this brief review is to address five of the current oxygen-sensing hypotheses...
December 7, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29213353/resveratrol-prevents-ros-induced-apoptosis-in-high-glucose-treated-retinal-capillary-endothelial-cells-via-the-activation-of-ampk-sirt1-pgc-1%C3%AE-pathway
#5
Jun Li, Songping Yu, Jia Ying, Tianyan Shi, Peipei Wang
Resveratrol (RSV) is used as a protective therapy against diabetic retinopathy. However, the mechanism(s) underlying this protective effect has not been fully elucidated. Bovine retinal capillary endothelial cells (BRECs), an in vitro model, were used to investigate the mechanism of RSV. Our results showed that high glucose induced significant cellular apoptosis in BRECs, which was accompanied by increased intracellular levels of reactive oxygen species (ROS) and cleaved caspase-3. The glucose-induced apoptosis and ROS elevation were both inhibited by RSV...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29212931/suppression-of-zika-virus-infection-and-replication-in-endothelial-cells-and-astrocytes-by-pka-inhibitor-pki-14-22
#6
Fan Cheng, Suzane Ramos da Silva, I-Chueh Huang, Jae U Jung, Shou-Jiang Gao
The recent outbreak of Zika virus (ZIKV), a re-emerging flavivirus, and its associated neurological disorders, such as Guillain-Barré (GB) syndrome and microcephaly, have generated an urgent need for developing effective ZIKV vaccines and therapeutic agents. Here, we used human endothelial cells and astrocytes, both of which represent key cell types for ZIKV infection, to identify potential inhibitors for ZIKV replication. Because several pathways, including AMP-activated protein kinase (AMPK), protein kinase A (PKA), and mitogen-activated protein kinase (MAPK) signaling pathways, have been reported to play important roles in flavivirus replication, we tested inhibitors or agonists of these pathways for their effects on ZIKV replication...
December 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29212261/cordycepin-stimulates-autophagy-in-macrophages-and-prevents-atherosclerotic-plaque-formation-in-apoe-mice
#7
Xin Li, Yue Zhou, Xue Zhang, Xiaoxue Cao, Chongming Wu, Peng Guo
Autophagy in macrophages plays a key role in the pathogenesis and progression of atherosclerosis and has become a potential therapeutic target. Here we show that cordycepin (Cpn), a natural derivative of adenosine, markedly reduced atherosclerotic plaque and ameliorated associated symptoms such as dyslipidemia, hyperglycemia and inflammation in ApoE-/- mice. Supplementation of Cpn dose-dependently inhibited oxLDL-elicited foam cell formation and modulated intracellular cholesterol homeostasis by inhibiting cholesterol uptake and promoting cholesterol efflux in RAW264...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212260/bioenergetics-of-acquired-cisplatin-resistant-h1299-non-small-cell-lung-cancer-and-p31-mesothelioma-cells
#8
Fintan Geoghegan, Robert J Buckland, Eric T Rogers, Karima Khalifa, Emma B O'Connor, Mary F Rooney, Parviz Behnam-Motlagh, Torbjörn K Nilsson, Kjell Grankvist, Richard K Porter
Acquired cisplatin resistance is a common feature of tumours following cancer treatment with cisplatin and also of non-small cell lung cancer (H1299) and mesothelioma (P31) cell lines exposed to cisplatin. To elucidate the cellular basis of acquired cisplatin resistance, a comprehensive bioenergetic analysis was undertaken. We demonstrate that cellular oxygen consumption was significantly decreased in cisplatin resistant cells and that the reduction was primarily due to reduced mitochondrial activity as a result of reduced mitochondrial abundance...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29209172/the-role-of-netrin-1-in-improving-functional-recovery-through-autophagy-stimulation-following-spinal-cord-injury-in-rats
#9
Liangjie Bai, Xifan Mei, Yanfeng Wang, Yajiang Yuan, Yunlong Bi, Gang Li, Hongyu Wang, Peng Yan, Gang Lv
Our previous findings indicated that treatment with Netrin-1 could improve functional recovery through the stimulation of autophagy, by activating the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway in rats following spinal cord injury (SCI). However, the underlying mechanisms were not elucidated. The purpose of this study was to investigate the underlying mechanisms by which Netrin-1 promotes autophagy and improves functional recovery after SCI. Following controlled SCI in Sprague-Dawley rats, we observed that the autophagic flux in neurons was impaired, as reflected by the accumulation of light chain 3-II (LC3-II)-positive and LC3-positive autophagosomes (APs), accompanied by the accumulation of the autophagic substrate, Sequestosome 1 (SQSTM1; also known as p62)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29208771/advanced-iron-overload-cardiomyopathy-in-a-genetic-murine-model-is-rescued-by-resveratrol-therapy
#10
Subhash K Das, Pavel Zhabyeyev, Ratnadeep Basu, Vaibhav B Patel, Jason R B Dyck, Zamaneh Kassiri, Gavin Y Oudit
Iron-overload cardiomyopathy is prevalent on a worldwide basis and is a major co-morbidity in patients with genetic hemochromatosis and secondary iron overload. Therapies are limited in part due to lack of a valid pre-clinical model, which recapitulates advanced iron-overload cardiomyopathy. Male hemojuvelin knockout (HJVKO) mice, which lack hemojuvelin (HJV), a bone morphogenetic co-receptor protein required for hepcidin expression and systemic iron homeostasis, were fed a high iron diet starting at 4 weeks of age for a duration of 1 year...
December 5, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29207101/diosgenin-prevents-high-fat-diet-induced-rat-non-alcoholic-fatty-liver-disease-through-the-ampk-and-lxr-signaling-pathways
#11
Silu Cheng, Shufang Liang, Qun Liu, Zhengting Deng, Yuanhui Zhang, Juan Du, Ya'ni Zhang, Shu Li, Binbin Cheng, Changquan Ling
Non-alcoholic fatty liver disease (NAFLD) is a major public health concern worldwide. The aim of the present study was to observe the effect of diosgenin on NAFLD and investigate the underlying mechanisms. Diosgenin treatment increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in HepG2 cells. Diosgenin significantly inhibited high glucose (HG)-induced triglyceride (TG) accumulation and sterol regulatory element‑binding protein-1c (SREBP-1c) mRNA increase in HepG2 cells, which were partially abolished by the AMPK inhibitor compound C...
November 28, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29207028/role-of-the-cofilin-2-gene-in-regulating-the-myosin-heavy-chain-genes-in-mouse-myoblast-c2c12-cells
#12
Hongyan Zhu, Huixin Yang, Song Zhao, Junfeng Zhang, Dan Liu, Yumin Tian, Zhiyi Shen, Yuhong Su
The cofilin 2 (CFL2) and myosin heavy chain (MyHC) genes play a key role in muscle development and myofibrillar formation. The aim of the present study was to investigate the effect of CFL2 on genes involved in fiber formation and the mechanisms underlying this process. Undifferentiated and differentiated C2C12 cells (UDT and DT, respectively) were transfected with CFL2 small interfering RNA (siRNA). CFL2 mRNA and protein levels were assessed using reverse transcription polymerase chain reaction (RT-PCR) and western blotting, respectively...
November 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29207025/anti-obesity-effects-of-pectinase-and-cellulase-enzyme%C3%A2-treated-ecklonia%C3%A2-cava-extract-in-high%C3%A2-fat-diet%C3%A2-fed-c57bl-6n-mice
#13
In-Hye Kim, Jung-Wook Choi, Min-Kyeong Lee, Chang-Ju Kwon, Taek-Jeong Nam
The present study investigated the anti‑obesity effects of enzyme‑treated Ecklonia cava extract (EEc) in C57BL/6N mice with high‑fat diet (HFD)‑induced obesity. The EEc was separated and purified with the digestive enzymes pectinase (Rapidase X‑Press L) and cellulase (Rohament CL) and its effects on the progression of HFD‑induced obesity were examined over 10 weeks. The mice were divided into 6 groups (n=10/group) as follows: Normal diet group, HFD group, mice fed a HFD with 25 mg/kg/day Garcinia cambogia extract and mice fed a HFD with 5, 25 or 150 mg/kg/day EEc (EHD groups)...
November 28, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29205673/mechanisms-of-ampk-in-the-maintenance-of-atp-balance-during-energy-metabolism
#14
REVIEW
Rong Ke, Qicao Xu, Cong Li, Lingyu Luo, Deqiang Huang
AMP-activated protein kinase (AMPK) is a conserved sensor of cellular energy change and is activated by increased AMP/ATP and/or ADP/ATP ratios. AMPK maintains the energy balance by decreasing the ATP-consuming processes such as transcription of synthetic fat genes and rRNA, the translation of ribosomal proteins, synthesis of cholesterol and fatty acid, while the metabolic pathways such as glucose and fatty transport, fatty acid oxidation, autophagy, mitochondrial synthesis and oxidative metabolism are increased to preserve ATP during energy deficiency...
December 4, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29199177/inhibition-of-glycogen-phosphorylase-stimulates-ventromedial-hypothalamic-nucleus-amp-activated-protein-kinase-activity-and-neuronal-nitric-oxide-synthase-protein-expression-in-male-rats
#15
Hussain N Alhamami, Ayed Alshamrani, Karen P Briski
The glucose polymer glycogen is a vital fuel reserve in the brain. The mediobasal hypothalamic energy sensor AMP-activated protein kinase (AMPK) maintains glucostasis via neurotransmitter mechanisms that suppress [γ-aminobutyric acid; GABA] or stimulate [nitric oxide; steroidogenic factor-1 (SF1)] counter-regulatory outflow. This study investigated whether glycogen-derived fuel supply is a critical screened variable in ventromedial hypothalamic nucleus (VMN) monitoring of neuro-metabolic stability during glucostasis and/or insulin (I)-induced hypoglycemia...
December 2017: Physiological Reports
https://www.readbyqxmd.com/read/29198059/metabolic-effects-of-physiological-levels-of-caffeine-in-myotubes
#16
Jamie K Schnuck, Lacey M Gould, Hailey A Parry, Michele A Johnson, Nicholas P Gannon, Kyle L Sunderland, Roger A Vaughan
Caffeine has been shown to stimulate multiple major regulators of cell energetics including AMP-activated protein kinase (AMPK) and Ca2+/calmodulin-dependent protein kinase II (CaMKII). Additionally, caffeine induces peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial biogenesis. While caffeine enhances oxidative metabolism, experimental concentrations often exceed physiologically attainable concentrations through diet. This work measured the effects of low-level caffeine on cellular metabolism and gene expression in myotubes, as well as the dependence of caffeine's effects on the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPARβ/δ)...
December 3, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29193691/purple-potato-extract-promotes-intestinal-epithelial-differentiation-and-barrier-function-by-activating-amp-activated-protein-kinase
#17
Xiaofei Sun, Min Du, Duroy A Navarre, Mei-Jun Zhu
SCOPE: Perturbation of gut epithelial barrier function induces inflammation and other health problems that originate from the gut. Purple potato contains a high content of beneficial polyphenolic compounds. The objective of this study was to evaluate the effect of purple potato extract (PPE) on intestinal differentiation and barrier function, and explore its underlying mechanism using Caco-2 cells and ex vivo cultured gut tissues. METHODS AND RESULTS: PPE increased transepithelial electrical resistance and decreased FITC-dextran paracellular flux in Caco-2 cells, which were associated with strengthened intestinal epithelial differentiation in both Caco-2 cells and ex vivo guts...
November 28, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29193585/unravelling-the-carbohydrate-binding-preferences-of-the-carbohydrate-binding-modules-of-amp-activated-protein-kinase
#18
Jesse Mobbs, Alex di Paolo, Riley Metcalfe, Emily Selig, David Stapleton, Michael Griffin, Paul Gooley
The β-subunit of AMP-activated protein kinase (AMPK), which exists as two isoforms (β1 and β2) in humans, has a Carbohydrate Binding Module (CBM) that interacts with glycogen. While the β1- and β2-CBMs are structurally similar, with strictly conserved ligand-contact residues, they show different carbohydrate affinities. β2-CBM shows the strongest affinity for both branched and unbranched oligosaccharides and we have recently shown that a Thr insertion in β2-CBM (Thr101) forms a pocket to accommodate branches...
November 30, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29192322/%C3%AF-3-polyunsaturated-fatty-acids-induce-cell-death-through-apoptosis-and-autophagy-in-glioblastoma-cells-in-vitro-and-in-vivo
#19
Soyeon Kim, Kaipeng Jing, Soyeon Shin, Soyeon Jeong, Seung-Hyeon Han, Heyrim Oh, Yoon-Seon Yoo, Jeongsu Han, Young-Joo Jeon, Jun-Young Heo, Gi-Ryang Kweon, Seung-Kiel Park, Jong-Il Park, Tong Wu, Kyu Lim
Among brain tumors, glioblastoma (GBM) is the most aggressive type and is associated with the lowest patient survival rate. Numerous lines of evidence have established that omega-3-polyunsaturated fatty acids (ω3-PUFAs) have potential for the prevention and therapy of several types of cancers. Docosahexaenoic acid (DHA), an ω3-PUFA, was reported to inhibit growth and induce apoptotic and autophagic cell death in several cancer cell lines; however, its effects on GBM cells are still unknown. in the present study, we examined the cytotoxic effect of DHA on the GBM cell lines, D54MG, U87MG, U251MG and GL261...
January 2018: Oncology Reports
https://www.readbyqxmd.com/read/29192063/mechanism-of-inhibition-of-taurolithocholate-induced-retrieval-of-plasma-membrane-mrp2-by-cyclic-amp-and-tauroursodeoxycholate
#20
Se Won Park, Cynthia R L Webster, Mohammed S Anwer
Taurolithocholate (TLC) produces cholestasis by inhibiting biliary solute secretion in part by retrieving MRP2 from the plasma membrane (PM). Tauroursodeoxycholate (TUDC) and cAMP reverse TLC-induced cholestasis by inhibiting TLC-induced retrieval of MRP2. However, cellular mechanisms for this reversal are incompletely understood. Recently, we reported that TLC decreases PM-MRP2 by activating PKCε followed by phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS). Thus, cAMP and TUDC may reverse TLC-induced cholestasis by inhibiting the TLC/PKCε/MARCKS phosphorylation pathway...
December 2017: Physiological Reports
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