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https://www.readbyqxmd.com/read/28432301/ampk-signaling-in-the-nucleus-accumbens-core-mediates-cue-induced-reinstatement-of-cocaine-seeking
#1
Xue-Jiao Gao, Kai Yuan, Lu Cao, Wei Yan, Yi-Xiao Luo, Min Jian, Jian-Feng Liu, Qin Fang, Ji-Shi Wang, Ying Han, Jie Shi, Lin Lu
Relapse to drug seeking can be caused by exposure to drug-associated cues, provoking drug craving even after prolonged abstinence. Recent studies demonstrated that AMP-activated protein kinase (AMPK) regulates neuronal morphology and membrane excitability in neurons. Here, we investigated the role of AMPK activity in the nucleus accumbens (NAc) in relapse to cocaine seeking. We found that exposure to drug-related cues reinstated cocaine-seeking behavior and increased AMPK and p70s6k phosphorylation in the NAc core but not shell...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28409163/pgc1%C3%AE-activators-mitigate-diabetic-tubulopathy-by-improving-mitochondrial-dynamics-and-quality-control
#2
So-Young Lee, Jun Mo Kang, Dong-Jin Kim, Seon Hwa Park, Hye Yun Jeong, Yu Ho Lee, Yang Gyun Kim, Dong Ho Yang, Sang Ho Lee
Purpose. In this study, we investigated the effect of PGC1α activators on mitochondrial fusion, fission, and autophagic quality control in renal tubular cells in a diabetic environment in vivo and in vitro. We also examined whether the upregulation of PGC1α attenuates diabetic tubulopathy by normalizing mitochondrial homeostasis. Methods. HKC8 cells were subjected to high-glucose conditions (30 mM D-glucose). Diabetes was induced with streptozotocin (STZ, 50 mg/kg i.p. for 5 days) in male C57/BL6J mice...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28407446/doping-control-study-of-aicar-in-postrace-urine-and-plasma-samples-from-horses
#3
Jenny K Y Wong, Wai Him Kwok, George H M Chan, Timmy L S Choi, Emmie N M Ho, Murielle Jaubert, Ludovic Bailly-Chouriberry, Yves Bonnaire, Adam Cawley, H Ming Williams, John Keledjian, Lydia Brooks, Adam Chambers, Yuanyuan Lin, Terence S M Wan
Acadesine, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, commonly known as AICAR, is a naturally occurring adenosine monophosphate-activated protein kinase (AMPK) activator in many mammals including humans and horses. AICAR has attracted considerable attention recently in the field of doping control due to a study showing enhancement of endurance performance in unexercised or untrained mice, resulting in the term "exercise pill". Its use has been classified as gene doping by the World Anti-Doping Agency (WADA), and since it is endogenous, it may only be possible to control deliberate administration of AICAR to racehorses after establishment of an appropriate threshold...
April 13, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28387458/anti-tumorigenic-potential-of-a-novel-orlistat-aicar-combination-in-prostate-cancer-cells
#4
Clayton Wright, Anand Krishnan V Iyer, Vivek Kaushik, Neelam Azad
Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in men worldwide. Fatty acid synthase (FASN) is reported to be overexpressed in several cancers including PCa, and this has led to clinical cancer treatments that utilize various FASN inhibitors such as the anti-obesity drug, Orlistat. However, pharmacological limitations have impeded the progress in cancer treatments expected thus far with FASN inhibition. In this study, we investigated a novel therapeutic combination to enhance the toxic potential of Orlistat in three different PCa cell-lines (DU145, PC3, and LNCaP)...
April 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28360860/acanthoic-acid-can-partially-prevent-alcohol-exposure-induced-liver-lipid-deposition-and-inflammation
#5
You-Li Yao, Xin Han, Zhi-Man Li, Li-Hua Lian, Ji-Xing Nan, Yan-Ling Wu
Aims: The present study aims to detect the effect of acanthoic acid (AA) on alcohol exposure-induced liver lipid deposition and inflammation, and to explore the mechanisms. Methods: C57BL/6 mice were pretreated with single dose of AA (20 and 40 mg/kg) by oral gavage or equal volume of saline, and then exposed to three doses of ethanol (5 g/kg body weight, 25%, w/v) by gavage within 24 h. The mice were sacrificed at 6 h after the last ethanol dosing. Serum and hepatic indexes were detected by western blot, RT-PCR, and histopathological assay...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28325600/synthesis-and-anti-cancer-activities-of-new-sulfonamides-4-substituted-triazolyl-nucleosides
#6
Soukaina Alaoui, Maeva Dufies, Mohsine Driowya, Luc Demange, Khalid Bougrin, Guillaume Robert, Patrick Auberger, Gilles Pagès, Rachid Benhida
Nucleoside analogues are among the most known drugs commonly used in antiviral and anticancer chemotherapies. Among them, those featuring a five-membered ring nucleobase are of utmost interest such as the anti-cancer agent AICAR or the anti-viral drug ribavirin. Despite its low activity in vitro in different cell lines, AICAR is under clinical development for several pathologies, thanks to its original mode of action. Indeed, AICAR induced autophagy cell death and is able, following this mechanism, to circumvent resistance to apoptotic drugs including kinase inhibitors currently on the market...
May 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28298333/multiple-ampk-activators-inhibit-l-carnitine-uptake-in-c2c12-skeletal-muscle-myotubes
#7
Andy Shaw, Stewart Jeromson, Kenneth R Watterson, John D Pediani, Iain Gallagher, Tim Whalley, Gillian Dreczkowski, Naomi Brooks, Stuart Galloway, D Lee Hamilton
Mutations in the gene that encodes the principal L-Carnitine transporter, OCTN2, can lead to a reduced intracellular L-Carnitine pool and the disease Primary Carnitine Deficiency. L-Carnitine supplementation is used therapeutically to increase intracellular L-Carnitine. As AMPK and insulin regulate fat metabolism and substrate uptake we hypothesised that AMPK activating compounds and insulin would increase L-Carnitine uptake in C2C12 myotubes. The cells express all three OCTN transporters at the mRNA level and immunohistochemistry confirmed expression at the protein level...
March 15, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28244615/geniposide-protects-pancreatic-%C3%AE-cells-from-high-glucose-mediated-injury-by-activation-of-amp-activated-protein-kinase
#8
Chunyan Liu, Yanan Hao, Fei Yin, Yonglan Zhang, Jianhui Liu
Our previous works indicated that geniposide could regulate glucose-stimulated insulin secretion (GSIS), and improved chronic high glucose-induced dysfunctions in pancreatic β cells, but the molecular mechanisms remain largely unknown. In the present study, we investigated the role of 5'-AMP-activated protein kinase (AMPK) in high glucose induced cell injury and explored the associated molecular mechanisms in rat INS-1 pancreatic β cells. Data suggested that geniposide obviously prevented the cell damage induced by high (25 mM) glucose in INS-1 cells, which increased the protein levels of cell apoptosis-associated enzymes, including heme oxygenase-1 (HO-1), and Bcl-2, but apparently attenuated the protein level of Bax, an apoptotic protein...
May 2017: Cell Biology International
https://www.readbyqxmd.com/read/28235712/ampk-activation-reduces-the-number-of-atheromata-macrophages-in-apoe-deficient-mice
#9
Jing Wang, Ang Ma, Ming Zhao, Haibo Zhu
BACKGROUND AND AIMS: CC chemokine receptor 2 (Ccr2) governs migration of inflammatory Ly6C(hi) monocytes from the bone marrow (BM) to the circulating blood, which is a key step for macrophage accumulation during progression of atherosclerosis. Hyperlipidemia is often accompanied by low AMP-activated kinase (AMPK) activity and increased expression of Ccr2. The aim of this study was to examine whether there is a link between AMPK and chemokine networks. METHODS: ApoE(-/-) mice were fed a western diet and treated daily with AMPK activators (AICAR, A769662, or Metformin) or vehicle for 10 weeks...
March 2017: Atherosclerosis
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
#10
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
#11
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...
April 2017: Diabetologia
https://www.readbyqxmd.com/read/28186975/amp-activated-protein-kinase-reduces-inflammatory-responses-and-cellular-senescence-in-pulmonary-emphysema
#12
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)...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28180061/kinase-suppressor-of-ras-2-ksr2-expression-in-the-brain-regulates-energy-balance-and-glucose-homeostasis
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28041982/4-nonylphenol-induces-autophagy-and-attenuates-mtor-p70s6k-4ebp1-signaling-by-modulating-ampk-activation-in-sertoli-cells
#20
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
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