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Shi-Hong Gu, Yun-Chih Hsieh, Pei-Ling Lin
Our previous studies showed that adenosine 5'-monophosphate-activated protein kinase (AMPK)/the target of rapamycin (TOR) signaling is involved in prothoracicotropic hormone (PTTH)-stimulated ecdysteroidogenesis in Bombyx mori prothoracic glands (PGs). In the present study, we further investigated the signaling involved in PTTH-stimulated phosphorylation of 4E-BP. We found that 4E-BP phosphorylation stimulated by PTTH was partially reduced in Ca(2+)-free medium, indicating the involvement of Ca(2+). In addition, we found that a potent and specific inhibitor of phospholipase C (PLC), U73122, greatly inhibited 4E-BP phosphorylation...
October 14, 2016: Journal of Insect Physiology
Luis Sala-Icardo, Amalia Lamana, Ana María Ortiz, Elena García Lorenzo, Pablo Moreno Fresneda, Rosario García-Vicuña, Isidoro González-Álvaro
OBJECTIVE: To analyze the effect of single nucleotide polymorphisms (SNPs) with well-known functional impact of methylenetetrahydrofolatereductase (MTHFR; rs1801131 and rs1801133), the membrane transporter ABCB1 (rs1045642), the AICAR transformylase/IMP cyclohydrolase (ATIC; rs2372536) and folyl-polyglutamatesynthetase (FPGS; rs1544105), on liver and bone marrow toxicity of methotrexate (MTX). PATIENTS AND METHODS: We analyzed 1415 visits from 350 patients of the PEARL (Princesa Early Arthritis Register Longitudinal) study: (732 with MTX, 683 without MTX)...
October 14, 2016: Reumatología Clinica
Lezi Chen, Quan Chen, Guosan Deng, Wenbin Xie, Jihong Lian, Mian Wang, Huilan Zhu
Recent studies suggest that forced activation of AMP-activated protein kinase (AMPK) could inhibit melanoma cell proliferation. In this report, we evaluated the anti-melanoma cell activity by a novel small-molecular AMPK activator, GSK621. Treatment of GSK621 decreased survival and proliferation of human melanoma cells (A375, WM-115 and SK-Mel-2 lines), which was accompanied by activation of caspase-3/-9 and apoptosis. Reversely, caspase inhibitors attenuated GSK621-induced cytotoxicity against melanoma cells...
October 14, 2016: Biochemical and Biophysical Research Communications
Luciano Galdieri, Himavanth Gatla, Ivana Vancurova, Ales Vancura
AMP-activated protein kinase (AMPK) is an energy sensor and master regulator of metabolism. AMPK functions as a fuel gauge monitoring systemic and cellular energy status. Activation of AMPK occurs when the intracellular AMP/ATP ratio increases and leads to a metabolic switch from anabolism to catabolism. AMPK phosphorylates and inhibits acetyl-CoA carboxylase (ACC), which catalyzes carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting reaction in de-novo synthesis of fatty acids. AMPK thus regulates homeostasis of acetyl-CoA, a key metabolite at the crossroads of metabolism, signaling, chromatin structure, and transcription...
October 12, 2016: Journal of Biological Chemistry
Delphine Albrecht, Johanna Ceschin, Jim Dompierre, Florian Gueniot, Benoît Pinson, Bertrand Daignan-Fornier
Identifying synthetic lethal interactions has emerged as a promising new therapeutic approach aimed at targeting cancer cells directly. Here, we used the yeast Saccharomyces cerevisiae as a simple eukaryotic model to screen for mutations resulting in a synthetic lethality with 5-Amino-4-Imidazole CarboxAmide Ribonucleoside (AICAR) treatment. Indeed, AICAR has been reported to inhibit the proliferation of multiple cancer cell lines. Here, we found that loss of several histone-modifying enzymes, including Bre1 (histone H2B ubiquitination) and Set1 (histone H3 lysine 4 methylation), greatly enhanced AICAR inhibition on growth via combined-effects of both the drug and the mutations on G1 cyclins...
October 5, 2016: Genetics
Bo-Hwa Choi, Da-Hyun Lee, Jin Kim, Ju-Hee Kang, Chang-Shin Park
Generally, both lipopolysaccharide (LPS)- and hypoxia-induced nuclear factor kappa B (NF-κB) effects are alleviated through differential posttranslational modification of NF-κB phosphorylation after pretreatment with 5´-AMP-activated protein kinase (AMPK) activators such as 5´-aminoimidazole-4-carboxamide ribonucleotide (AICAR) or the hypoglycemic agent metformin. We found that AICAR or metformin acts as a regulator of LPS/NF-κB-or hypoxia/NF-κB-mediated cyclooxygenase induction by an AMPK-dependent mechanism with interactions between p65-NF-κB phosphorylation and acetylation, including in a human bladder cancer cell line (T24)...
September 2016: International Neurourology Journal
Yong Yang, Ting Bai, You-Li Yao, De-Quan Zhang, Yan-Ling Wu, Li-Hua Lian, Ji-Xing Nan
Thymoquinone (TQ) is a biologically active compound isolated from the seeds of Nigella sativa L. (Ranuculaceae). This study investigated the hepato-protective effect of TQ on liver injury through AMP-activated protein kinase (AMPK) signaling in hepatic stellate cells (HSCs). In vitro, TGF-β time-dependently attenuated liver kinase B-1 (LKB1) and AMPK phosphorylation, which were blocked by pretreatment with TQ and AICAR (an activator of AMPK). TQ significantly inhibited collagen-Ι, α-SMA, TIMP-1 and enhanced MMP-13 expression, contributing to prevent TGF-β-induced human HSCs activation...
September 26, 2016: Toxicology Letters
Don-Kyu Kim, Yong-Hoon Kim, Yoon Seok Jung, Ki-Sun Kim, Jae-Ho Jeong, Yong-Soo Lee, Jae-Min Yuk, Byung-Chul Oh, Hyon E Choy, Steven Dooley, Martina U Muckenthaler, Chul-Ho Lee, Hueng-Sik Choi
Small heterodimer partner (SHP) is a transcriptional corepressor regulating diverse metabolic processes. Here, we show that SHP acts as an intrinsic negative regulator of iron homeostasis. SHP-deficient mice maintained on a high-iron diet showed increased serum hepcidin levels, decreased expression of the iron exporter ferroportin as well as iron accumulation compared to WT mice. Conversely, overexpression of either SHP or AMP-activated protein kinase (AMPK), a metabolic sensor inducing SHP expression, suppressed BMP6-induced hepcidin expression...
September 30, 2016: Scientific Reports
Qiyuan Yang, Xingwei Liang, Xiaofei Sun, Lupei Zhang, Xing Fu, Carl J Rogers, Anna Berim, Shuming Zhang, Songbo Wang, Bo Wang, Marc Foretz, Benoit Viollet, David R Gang, Buel D Rodgers, Mei-Jun Zhu, Min Du
Promoting brown adipose tissue (BAT) development is an attractive strategy for the treatment of obesity, as activated BAT dissipates energy through thermogenesis; however, the mechanisms controlling BAT formation are not fully understood. We hypothesized that as a master regulator of energy metabolism, AMP-activated protein kinase (AMPK) may play a direct role in the process and found that AMPKα1 (PRKAA1) ablation reduced Prdm16 expression and impaired BAT development. During early brown adipogenesis, the cellular levels of α-ketoglutarate (αKG), a key metabolite required for TET-mediated DNA demethylation, were profoundly increased and required for active DNA demethylation of the Prdm16 promoter...
October 11, 2016: Cell Metabolism
Stavros Kopsiaftis, Katie L Sullivan, Isha Garg, John A Taylor, Kevin P Claffey
: AMP-activated protein kinase (AMPK) is the central metabolic regulator of the cell and controls energy consumption based upon nutrient availability. Due to its role in energy regulation, AMPK has been implicated as a barrier for cancer progression and is suppressed in multiple cancers. To examine whether AMPK regulates bladder cancer cell growth, HTB2 and HT1376 bladder cells were treated with an AMPK activator, AICAR. AICAR treatment reduced proliferation and induced the expression of p27Kip1 (CDKN1B), which was mediated through an mTOR-dependent mechanism...
September 16, 2016: Molecular Cancer Research: MCR
Eijiro Yamada, Shuichi Okada, Claire C Bastie, Manu Vatish, Yasuyo Nakajima, Ryo Shibusawa, Atsushi Ozawa, Jeffrey E Pessin, Masanobu Yamada
We previously demonstrated that proto-oncogene Fyn decreased energy expenditure and increased metabolic phenotypes. Also Fyn decreased autophagy-mediated muscle mass by directly inhibiting LKB1 and stimulating STAT3 activities, respectively. AMPK, a downstream target of LKB1, was recently identified as a key molecule controlling autophagy. Here we identified that Fyn phosphorylates the α subunit of AMPK on Y436 and inhibits AMPK enzymatic activity without altering the assembly state of the AMPK heterotrimeric complex...
September 8, 2016: Oncotarget
Samy L Habib, Anamika Yadav, Dawit Kidane, Robert Weiss, Sitai Liang
Exposure of renal cells to high glucose (HG) during diabetes has been recently proposed to be involved in renal injury. In the present study, we investigated a potential mechanism by which AICAR treatment regulates the DNA repair enzyme, 8-oxoG-DNA glycosylase (OGG1) in renal proximal tubular mouse cells exposed to HG and in kidney of db/db mice. Cells treated with HG for 2 days show inhibition in OGG1 promoter activity as well as OGG1 and Nrf2 protein expression. In addition, activation of AMPK by AICAR resulted in an increase raptor phosphorylation at Ser(792) and leads to increase the promoter activity of OGG1 through upregulation of Nrf2...
September 9, 2016: Cell Cycle
Waqar Ahmad, Paul R Ebert
The metabolic disease, type 2 diabetes mellitus (T2DM), is a major risk factor for Alzheimer's disease (AD). This suggests that drugs such as metformin that are used to treat T2DM may also be therapeutic toward AD and indicates an interaction between AD and energy metabolism. In this study, we have investigated the effects of metformin and another T2DM drug, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) in C. elegans expressing human Aβ42. We found that Aβ expressed in muscle inhibited levamisole sensitive nicotinic acetylcholine receptors and that metformin delayed Aβ-linked paralysis and improved acetylcholine neurotransmission in these animals...
September 5, 2016: Molecular Neurobiology
Naoki Harada, Mikako Ishihara, Hiroko Horiuchi, Yuta Ito, Hiromitsu Tabata, Yasushi A Suzuki, Yoshihisa Nakano, Ryoichi Yamaji, Hiroshi Inui
This study investigated the effects of mogrol, an aglycone of mogrosides from Siraitia grosvenorii, on adipogenesis in 3T3-L1 preadipocytes. Mogrol, but not mogrosides, suppressed triglyceride accumulation by affecting early (days 0-2) and late (days 4-8), but not middle (days 2-4), differentiation stages. At the late stage, mogrol increased AMP-activated protein kinase (AMPK) phosphorylation and reduced glycerol-3-phosphate dehydrogenase activity. At the early stage, mogrol promoted AMPK phosphorylation, inhibited the induction of CCAAT/enhancer-binding protein β (C/EBPβ; a master regulator of adipogenesis), and reduced 3T3-L1 cell contents (e...
2016: PloS One
Laurent Bultot, Thomas E Jensen, Yu-Chiang Lai, Agnete L B Madsen, Caterina Collodet, Samanta Kviklyte, Maria Deak, Arash Yavari, Marc Foretz, Sahar Ghaffari, Mohamed Bellahcene, Houman Ashrafian, Mark H Rider, Erik A Richter, Kei Sakamoto
AMP-activated protein kinase (AMPK) plays diverse roles and coordinates complex metabolic pathways for maintenance of energy homeostasis. This could be explained by the fact that AMPK exists as multiple heterotrimer complexes comprising a catalytic α-subunit (α1 and α2) and regulatory β (β1 and β2)- and γ (γ1, γ2, γ3)-subunits, which are uniquely distributed across different cell types. There has been keen interest in developing specific and isoform-selective AMPK-activating drugs for therapeutic use and also as research tools...
October 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
Marcel Boß, Yvette Newbatt, Sahil Gupta, Ian Collins, Bernhard Brüne, Dmitry Namgaladze
Obesity-associated insulin resistance is driven by inflammatory processes in response to metabolic overload. Obesity-associated inflammation can be recapitulated in cell culture by exposing macrophages to saturated fatty acids (SFA), and endoplasmic reticulum (ER) stress responses essentially contribute to pro-inflammatory signalling. AMP-activated protein kinase (AMPK) is a central metabolic regulator with established anti-inflammatory actions. Whether pharmacological AMPK activation suppresses SFA-induced inflammation in a human system is unclear...
2016: Scientific Reports
Mohammad M Al-Bataineh, Hui Li, Kazuhiro Ohmi, Fan Gong, Allison Marciszyn, Sajid Naveed, Xiaoqing Zhu, Dietbert Neumann, Qi Wu, Lei Cheng, Robert A Fenton, Núria M Pastor-Soler, Kenneth R Hallows
Aquaporin-2 (AQP2) is essential to maintain body water homeostasis. AQP2 traffics from intracellular vesicles to the apical membrane of kidney collecting duct principal cells in response to vasopressin (AVP), a hormone released with low intravascular volume, which causes decreased kidney perfusion. Decreased kidney perfusion activates AMP-activated kinase (AMPK), a metabolic sensor that inhibits the activity of several transport proteins. We hypothesized that AMPK activation also inhibits AQP2 function. These putative AMPK effects could protect interstitial ionic gradients required for urinary concentration during metabolic stress when low intravascular volume induces AVP release...
August 17, 2016: American Journal of Physiology. Renal Physiology
Baolin Chen, Qiang Wu, Zhaojun Xiong, Yuedong Ma, Sha Yu, Dandan Chen, Shengwen Huang, Yugang Dong
Control of cardiac muscle mass is thought to be determined by a dynamic balance of protein synthesis and degradation. Recent studies have demonstrated that atrophy-related forkhead box O 3a (FOXO3a)/muscle atrophy F-box (MAFbx) signaling pathway plays a central role in the modulation of proteolysis and exert inhibitory effect on cardiomyocyte hypertrophy. In this study, we tested the hypothesis that adenosine monophosphate-activated protein kinase (AMPK) activation attenuates cardiomyocyte hypertrophy by regulating FOXO3a/MAFbx signaling pathway and its downstream protein degradation...
September 2016: Acta Biochimica et Biophysica Sinica
Dzmitry Matsiukevich, Giovanna Piraino, Lindsey R Klingbeil, Paul W Hake, Vivian Wolfe, Michael O'Connor, Basilia Zingarelli
The development of myocardial dysfunction in patients with hemorrhagic shock is significantly impacted by the patient age. AMP-activated protein kinase (AMPK) is a pivotal orchestrator of energy homeostasis, which coordinates metabolic recovery after cellular stress. We investigated whether AMPK-regulated pathways are age-dependent in hemorrhage-induced myocardial injury and whether AMPK activation by 5-amino-4-imidazole carboxamide riboside (AICAR) affords cardioprotective effects. Anesthetized C57/BL6 young (3-5 months old) and mature male mice (9-12 months old) were subjected to hemorrhagic shock by blood withdrawing followed by resuscitation with shed blood and Lactated Ringer's solution...
August 10, 2016: Shock
Tong-Yan Liu, Xiao-Qing Xiong, Xing-Sheng Ren, Ming-Xia Zhao, Chang-Xiang Shi, Jue-Jin Wang, Ye-Bo Zhou, Feng Zhang, Ying Han, Xing-Ya Gao, Qi Chen, Yue-Hua Li, Yu-Ming Kang, Guo-Qing Zhu
Fibronectin type III domain-containing 5 (FNDC5) protein induces browning of subcutaneous fat, and mediates beneficial effects of exercise on metabolism. However, whether FNDC5 is associated with hepatic steatosis, autophagy, fatty acid oxidation (FAO) and lipogenesis remains unknown. Herein, we show the roles and mechanisms of FNDC5 in hepatic steatosis, autophagy and lipid metabolism. Fasted FNDC5(-/-) mice exhibited severe steatosis, reduced autophagy and FAO, and enhanced lipogenesis in liver compared with WT mice...
August 8, 2016: Diabetes
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