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https://www.readbyqxmd.com/read/28211632/amp-activated-protein-kinase-activator-a-769662-increases-intracellular-calcium-and-atp-release-from-astrocytes-in-an-ampk-independent-manner
#1
Julia M Vlachaki Walker, Josephine L Robb, Ana M Cruz, Amrinder Malhi, Paul G Weightman Potter, Michael L J Ashford, Rory J McCrimmon, Kate L J Ellacott, Craig Beall
AIM: Astrocytes are the main sources of extracellular ATP (eATP) within the brain, which functions as a gliotransmitter, capable of modulating neuronal and astrocytic activity. These cells play an important role in regulating energy homeostasis partly via astrocyte-derived ATP. Given the role of AMPK in regulating intracellular ATP levels, we hypothesised that AMPK may alter ATP release from astrocytes. METHODS: Measurements of ATP release were made from human U373 astrocytoma cells, primary mouse hypothalamic (HTAS) and cortical astrocytes (CRTAS) and wild type and AMPK α1/α2 null mouse embryonic fibroblasts (MEFs)...
February 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28188334/aicar-ameliorates-high-fat-diet-associated-pathophysiology-in-mouse-and-ex-vivo-models-independent-of-adiponectin
#2
Emma Börgeson, Ville Wallenius, Gulam H Syed, Manjula Darshi, Juan Lantero Rodriguez, Christina Biörserud, Malin Ragnmark Ek, Per Björklund, Marianne Quiding-Järbrink, Lars Fändriks, Catherine Godson, Kumar Sharma
AIMS/HYPOTHESIS: In this study, we aimed to evaluate the therapeutic potential of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMP-activated protein kinase, for ameliorating high-fat diet (HFD)-induced pathophysiology in mice. We also aimed to determine whether the beneficial effects of AICAR were dependent on adiponectin. Furthermore, human adipose tissue was used to examine the effect of AICAR ex vivo. METHODS: Six-week-old male C57BL/6J wild-type and Adipoq (-/-) mice were fed a standard-fat diet (10% fat) or an HFD (60% fat) for 12 weeks and given vehicle or AICAR (500 μg/g) three times/week from weeks 4-12...
February 10, 2017: Diabetologia
https://www.readbyqxmd.com/read/28186975/amp-activated-protein-kinase-reduces-inflammatory-responses-and-cellular-senescence-in-pulmonary-emphysema
#3
Xiao-Yu Cheng, Yang-Yang Li, Cheng Huang, Jun Li, Hong-Wei Yao
Current drug therapy fails to reduce lung destruction of chronic obstructive pulmonary disease (COPD). AMP-activated protein kinase (AMPK) has emerged as an important integrator of signals that control energy balance and lipid metabolism. However, there are no studies regarding the role of AMPK in reducing inflammatory responses and cellular senescence during the development of emphysema. Therefore, we hypothesize that AMPK reduces inflammatroy responses, senescence, and lung injury. To test this hypothesis, human bronchial epithelial cells (BEAS-2B) and small airway epithelial cells (SAECs) were treated with cigarette smoke extract (CSE) in the presence of a specific AMPK activator (AICAR, 1 mM) and inhibitor (Compound C, 5 μM)...
February 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28180061/kinase-suppressor-of-ras-2-ksr2-expression-in-the-brain-regulates-energy-balance-and-glucose-homeostasis
#4
Lili Guo, Diane L Costanzo-Garvey, Deandra R Smith, Beth K Neilsen, Richard G MacDonald, Robert E Lewis
OBJECTIVE: Kinase Suppressor of Ras 2 (KSR2) is a molecular scaffold coordinating Raf/MEK/ERK signaling that is expressed at high levels in the brain. KSR2 disruption in humans and mice causes obesity and insulin resistance. Understanding the anatomical location and mechanism of KSR2 function should lead to a better understanding of physiological regulation over energy balance. METHODS: Mice bearing floxed alleles of KSR2 (KSR2(fl/fl)) were crossed with mice expressing the Cre recombinase expressed by the Nestin promoter (Nes-Cre) to produce Nes-CreKSR2(fl/fl) mice...
February 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28174693/fanconi-anemia-protein-fancd2-is-activated-by-aicar-a-modulator-of-ampk-and-cellular-energy-metabolism
#5
Min Jeong Chun, Hana Choi, Dong Wha Jun, Sunshin Kim, Yong-Nyun Kim, Soo-Youl Kim, Chang-Hun Lee
FANCD2 is a pivotal molecule in the pathogenesis of Fanconi anemia (FA), an autosomal recessive human syndrome with diverse clinical phenotypes, including cancer predisposition, short stature, and hematological abnormalities. In our previous study, we detected the functional association of FANC proteins, whose mutations are responsible for the onset of FA, with AMPK in response to DNA interstrand crosslinking lesions. Because AMPK is well known as a critical sensing molecule for cellular energy levels, we checked whether FANCD2 activation occurs after treatments affecting AMPK and/or cellular energy status...
February 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28121062/exposure-to-15-oxygen-in-vivo-up-regulates-cardioprotective-sur2a-without-affecting-erk1-2-and-akt-a-crucial-role-for-ampk
#6
Khaja Shameem Mohammed Abdul, Sofija Jovanović, Aleksandar Jovanović
SUR2A is an 'atypical' ABC protein that forms sarcolemmal ATP-sensitive K(+) (KATP ) channels by binding to inward rectifier Kir6.2. Manipulation with SUR2A levels has been suggested to be a promising therapeutic strategy against ischaemic heart diseases and other diseases where increased heart resistance to stress is beneficial. Some years ago, it has been reported that high-altitude residents have lower mortality rates for ischaemic heart disease. The purpose of this study was to determine whether SUR2A is regulated by mild-to-severe hypoxic conditions (15% oxygen; oxygen tension equivalent to 3000 m above sea level) and elucidate the underlying mechanism...
January 25, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28087254/anti-diabetic-drug-metformin-dilates-retinal-blood-vessels-through-activation-of-amp-activated-protein-kinase-in-rats
#7
Asami Mori, Eriko Ishikawa, Tomoyo Amano, Kenji Sakamoto, Tsutomu Nakahara
The aim of this study was to examine whether metformin, a biguanide anti-hyperglycemic drug, dilates retinal blood vessels in rats. Ocular fundus images were captured with an original high-resolution digital fundus camera in vivo and diameters of retinal blood vessels were measured. Both systemic blood pressure and heart rate were continuously recorded. Metformin (0.01-0.3mg/kg/min) increased diameters of retinal blood vessels in a dose-dependent manner. This retinal vasodilator effect of metformin was abolished by compound C, an inhibitor of AMP-activated protein kinase (AMPK), and N(G)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide (NO) synthase...
January 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28068384/hypoxia-regulates-mtorc1-mediated-keratinocyte-motility-and-migration-via-the-ampk-pathway
#8
Tiantian Yan, Junhui Zhang, Di Tang, Xingyue Zhang, Xupin Jiang, Liping Zhao, Qiong Zhang, Dongxia Zhang, Yuesheng Huang
Keratinocyte migration, the initial event and rate-limiting step in wound healing, plays a vital role in restoration of the intact skin barrier, also known as re-epithelialization. After acute tissue injury, hypoxic microenvironment gradually develops and acts as an early stimulus to initiate the healing process. Although we have previously found that hypoxia induces keratinocyte migration, the underlying mechanism remains unknown. Here, we first observed that hypoxia increased mTORC1 activity. Recombinant lentivirus vector and Rapamycin were used for silencing mTORC1 in HaCaT cells and primary mouse keratinocytes (MKs)...
2017: PloS One
https://www.readbyqxmd.com/read/28067669/targeting-deregulated-ampk-mtorc1-pathways-improves-muscle-function-in-myotonic-dystrophy-type-i
#9
Marielle Brockhoff, Nathalie Rion, Kathrin Chojnowska, Tatiana Wiktorowicz, Christopher Eickhorst, Beat Erne, Stephan Frank, Corrado Angelini, Denis Furling, Markus A Rüegg, Michael Sinnreich, Perrine Castets
Myotonic dystrophy type I (DM1) is a disabling multisystemic disease that predominantly affects skeletal muscle. It is caused by expanded CTG repeats in the 3'-UTR of the dystrophia myotonica protein kinase (DMPK) gene. RNA hairpins formed by elongated DMPK transcripts sequester RNA-binding proteins, leading to mis-splicing of numerous pre-mRNAs. Here, we have investigated whether DM1-associated muscle pathology is related to deregulation of central metabolic pathways, which may identify potential therapeutic targets for the disease...
February 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28052040/nuclear-receptor-retinoid-related-orphan-receptor-alpha-promotes-apoptosis-but-is-reduced-in-human-gastric-cancer
#10
Zhengguang Wang, Fangyuan Xiong, Xiaoshan Wang, Yijun Qi, Haoyuan Yu, Yong Zhu, Huaqing Zhu
Retinoid-related orphan receptor α (RORα) is a nuclear receptor, which regulates inflammation and immune responses, lipid metabolism and circadian rhythm. Although RORα suppresses breast tumor invasion, it is unknown whether RORα is dysregulated in gastric cancer leading to cellular survival. Therefore, we hypothesize that RORα is dysfunctional in gastric carcinoma and this causes decreased apoptosis in gastric cancer cells. To test this hypothesis, we employed human gastric cancer tissues with different stages to determine RORα expression, as well as in vitro human gastric cancer cells to determine how RORα is reduced during apoptosis...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28041982/4-nonylphenol-induces-autophagy-and-attenuates-mtor-p70s6k-4ebp1-signaling-by-modulating-ampk-activation-in-sertoli-cells
#11
Peng Duan, Chunhui Hu, Chao Quan, Tingting Yu, Wenting Huang, Wei Chen, Sha Tang, Yuqin Shi, Francis L Martin, Kedi Yang
The estrogenic chemical 4-nonylphenol (NP) is known to impair testicular devolopment and spermatogenesis in rodents. The objective of this study was to explore the effects of NP on autophagy induction and AMPK-mTOR signaling pathway in Sertoli cells (SCs), which are the "nursemaid cells" for meiosis of spermatocytes. In this study we exposed 7-week-old male rats to NP by intra-peritoneal injection at 0, 20, 50 or 100mg/kg body weight/2days for 20 consecutive days. Our results showed that exposure to NP dose-dependently induces the formation of autophagosomes in SCs, increases the expression of Beclin-1, the conversion of LC3-I to LC3-II and the mRNA expression of Atg3, Atg5, Atg7 and Atg12 in testis, and these effects are concomitant with the activation of AMPK, and the suppression of TSC2-mTOR-p70S6K/4EBP1 signaling cascade in testis...
February 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28008135/gfat1-phosphorylation-by-ampk-promotes-vegf-induced-angiogenesis
#12
Darya Zibrova, Franck Vandermoere, Olga Göransson, Mark Peggie, Karina V Mariño, Anne Knierim, Katrin Spengler, Cora Weigert, Benoit Viollet, Nicholas A Morrice, Kei Sakamoto, Regine Heller
Activation of AMP-activated protein kinase (AMPK) in endothelial cells regulates energy homeostasis, stress protection and angiogenesis, but the underlying mechanisms are incompletely understood. Using a label-free phosphoproteomic analysis, we identified glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1) as an AMPK substrate. GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc). In the present study, we tested the hypothesis that AMPK controls O-GlcNAc levels and function of endothelial cells via GFAT1 phosphorylation using biochemical, pharmacological, genetic and in vitro angiogenesis approaches...
22, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27997894/zedoarondiol-inhibits-platelet-derived-growth-factor-induced-vascular-smooth-muscle-cells-proliferation-via-regulating-amp-activated-protein-kinase-signaling-pathway
#13
Huimin Mao, Tianqi Tao, Dandan Song, Mi Liu, Xiaoren Wang, Xiuhua Liu, Dazhuo Shi
BACKGROUND/AIMS: Vascular smooth muscle cells (VSMCs) proliferation contributes significantly to atherosclerosis and in-stent restenosis. Platelet-derived growth factor-BB (PDGF-BB) plays a vital role in VSMCs proliferation. Zedoarondiol, a sesquiterpene lactone compound, has an anti-inflammatory activity. However, the role of zedoarondiol in PDGF-BB-mediated VSMCs proliferation remains unclear. In this study, we investigated the effects of zedoarondiol on PDGF-BB-induced VSMCs proliferation and explored the possible mechanisms...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27991529/the-biosynthetic-pathway-of-2-azahypoxanthine-in-fairy-ring-forming-fungus
#14
Tomohiro Suzuki, Naoki Yamamoto, Jae-Hoon Choi, Tomoyuki Takano, Yohei Sasaki, Yurika Terashima, Akinobu Ito, Hideo Dohra, Hirofumi Hirai, Yukino Nakamura, Kentaro Yano, Hirokazu Kawagishi
"Fairy rings" resulting from fungus-stimulated plant growth occur all over the world. In 2010, 2-azahypoxanthine (AHX) from a fungus Lepista sordida was identified as the "fairy" that stimulates plant growth. Furthermore, 2-aza-8-oxohypoxanthine (AOH) was isolated as a common metabolite of AHX in plants, and the endogenous existence of AHX and AOH in plants was proved. The structure of AHX allowed us to hypothesize that AHX was derived from 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). Thus, we performed a feeding experiment that supplied AICAR to L...
December 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27988363/in-vitro-antiglioma-action-of-indomethacin-is-mediated-via-amp-activated-protein-kinase-mtor-complex-1-signalling-pathway
#15
Aleksandar Pantovic, Mihajlo Bosnjak, Katarina Arsikin, Milica Kosic, Milos Mandic, Biljana Ristic, Jelena Tosic, Danica Grujicic, Aleksandra Isakovic, Nikola Micic, Vladimir Trajkovic, Ljubica Harhaji-Trajkovic
We investigated the role of the intracellular energy-sensing AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway in the in vitro antiglioma effect of the cyclooxygenase (COX) inhibitor indomethacin. Indomethacin was more potent than COX inhibitors diclofenac, naproxen, and ketoprofen in reducing the viability of U251 human glioma cells. Antiglioma effect of the drug was associated with p21 increase and G2M cell cycle arrest, as well as with oxidative stress, mitochondrial depolarization, caspase activation, and the induction of apoptosis...
December 14, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27957796/involvement-of-ampk-in-regulating-the-degradation-of-mad2b-under-high-glucose-in-neuronal-cells
#16
Xianfang Meng, Guangpin Chu, Chen Ye, Hui Tang, Ping Qiu, Yue Hu, Man Li, Chun Zhang
Although our recent study has demonstrated that mitotic spindle assembly checkpoint protein (MAD2B) mediates high glucose-induced neuronal apoptosis, the mechanisms for MAD2B degradation under hyperglycaemia have not yet been elucidated. In this study, we first found that the activation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) was decreased in neurons, accompanied with the increased expression of MAD2B. Mechanistically, we demonstrated that activation of AMPK with its activators such as AICAR and metformin decreased the expression of MAD2B, indicating a role of AMPK in regulating the expression of MAD2B...
December 13, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27916511/liqustri-lucidi-fructus-inhibits-hepatic-injury-and-functions-as-an-antioxidant-by-activation-of-amp-activated-protein-kinase-in%C3%A2-vivo-and-in%C3%A2-vitro
#17
Hye Lim Seo, Su Youn Baek, Eun Hye Lee, Ju-Hee Lee, Seul-Gi Lee, Kwang-Youn Kim, Mi Hee Jang, Min-Hui Park, Joung-Hee Kim, Keuk-Jun Kim, Hyeong Sik Lee, Soon-Cheol Ahn, Jong Rok Lee, Sook Jahr Park, Sang Chan Kim, Young Woo Kim
Medicinal herbs are used to treat or prevent various diseases, and function to regulate protective mechanisms as nutraceuticals. Fructus Ligustri lucidi is the fruit of Ligustrum lucidum and has been used for its tonic effects on the liver. This study was designed to examine the effects of Fructus Ligustri lucidi water extract (FLL) against severe oxidative stress and mitochondrial impairment in vivo and in vitro and to elucidate its cellular mechanisms of action. Treatment of HepG2 cells with arachidonic acid (AA) + iron successfully induced oxidative stress and apoptosis, as indicated by depletion of glutathione, formation of ROS, decreses in mitochondrial membrane potential (Δψm), and altered expression of apoptosis-related proteins, such as procaspase-3 and Bcl-xL...
January 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27906079/muscle-specific-loss-of-bmal1-leads-to-disrupted-tissue-glucose-metabolism-and-systemic-glucose-homeostasis
#18
Brianna D Harfmann, Elizabeth A Schroder, Maureen T Kachman, Brian A Hodge, Xiping Zhang, Karyn A Esser
BACKGROUND: Diabetes is the seventh leading cause of death in the USA, and disruption of circadian rhythms is gaining recognition as a contributing factor to disease prevalence. This disease is characterized by hyperglycemia and glucose intolerance and symptoms caused by failure to produce and/or respond to insulin. The skeletal muscle is a key insulin-sensitive metabolic tissue, taking up ~80 % of postprandial glucose. To address the role of the skeletal muscle molecular clock to insulin sensitivity and glucose tolerance, we generated an inducible skeletal muscle-specific Bmal1 (-/-) mouse (iMSBmal1 (-/-))...
March 30, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27898346/amp-kinase-promotes-bcl6-expression-in-both-mouse-and-human-t-cells
#19
Markus M Xie, Tohti Amet, Hong Liu, Qigui Yu, Alexander L Dent
The transcription factor Bcl6 is a master regulator of follicular helper T (TFH) cells, and understanding the signaling pathway that induces Bcl6 and TFH cell differentiation is therefore critical. IL-2 produced during T cell activation inhibits Bcl6 expression but how TFH cells evade IL-2 inhibition is not completely understood. Here we show that Bcl6 is highly up-regulated in activated CD4 T cells following glucose deprivation (GD), and this pathway is insensitive to inhibition by IL-2. Similar to GD, the glucose analog 2-deoxyglucose (2DG) inhibits glycolysis, and 2DG induced Bcl6 expression in activated CD4 T cells...
January 2017: Molecular Immunology
https://www.readbyqxmd.com/read/27878239/aicar-induces-mitochondrial-apoptosis-in-human-osteosarcoma-cells-through-an-ampk-dependent-pathway
#20
Masayuki Morishita, Teruya Kawamoto, Hitomi Hara, Yasuo Onishi, Takeshi Ueha, Masaya Minoda, Etsuko Katayama, Toshiyuki Takemori, Naomasa Fukase, Masahiro Kurosaka, Ryosuke Kuroda, Toshihiro Akisue
The AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) modulates cellular energy metabolism, and promotes mitochondrial proliferation and apoptosis. Previous studies have shown that AICAR has anticancer effects in various cancers, however the roles of AMPK and/or the effects of AICAR on osteosarcoma have not been reported. In the present study, we evaluated the effects of AICAR on tumor growth and mitochondrial apoptosis in human osteosarcoma both in vitro and in vivo...
January 2017: International Journal of Oncology
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