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O Awwad, F Coperchini, P Pignatti, M Denegri, S Massara, L Croce, C A Di Buduo, V Abbonante, A Balduini, L Chiovato, M Rotondi
PURPOSE: The AMPK-activator AICAR recently raised great interest for its anti-cancer properties. With specific regard to thyroid cancer, AICAR reduces cancer cell growth, invasion and metastasis. CXCL8, a chemokine with several recognized tumorigenic effects, is abundantly secreted in thyroid cancer microenvironment. The aim of this study was to investigate if AICAR could inhibit the basal and the TNFα-induced CXCL8 secretion in normal human thyroid cells (NHT) and in thyroid cancer cell lines TPC-1 and BCPAP (RET/PTC and BRAFV600e mutated, respectively)...
March 15, 2018: Journal of Endocrinological Investigation
Michael Mendler, Stefan Kopf, Jan B Groener, Christin Riedinger, Thomas H Fleming, Peter P Nawroth, Jürgen G Okun
AIMS: 5-Aminoimidazole-4-carboxamide riboside (AICAR) is an endogenous activator of AMPK, a central regulator of energy homeostasis. Loss and/or reduction of AMPK signaling plays an important role in the development of insulin resistance in type 2 diabetes. The loss of AMPK in diabetes could be due to a loss of AICAR. The aim of this study was to characterize urine levels of AICAR in diabetes and determine whether an association exists with respect to late complications, e.g., retinopathy, nephropathy and neuropathy...
March 15, 2018: Acta Diabetologica
Evgeniya A Malykh, Ivan A Butov, Anna B Ravcheeva, Alexander A Krylov, Sergey V Mashko, Nataliya V Stoynova
BACKGROUND: In the L-histidine (His) biosynthetic pathway of Escherichia coli, the first key enzyme, ATP-phosphoribosyltransferase (ATP-PRT, HisG), is subject to different types of inhibition. Eliminating the feedback inhibition of HisG by the His end product is an important step that enables the oversynthesis of His in breeding strains. However, the previously reported feedback inhibition-resistant mutant enzyme from E. coli, HisGE271K , is inhibited by purine nucleotides, particularly ADP and AMP, via competitive inhibition with its ATP substrate...
March 15, 2018: Microbial Cell Factories
Ji-Chang Wang, Xiong-Xiong Li, Xin Sun, Guang-Yue Li, Jing-Lan Sun, Yuan-Peng Ye, Long-Long Cong, Wei-Ming Li, Shao-Ying Lu, Jun Feng, Pei-Jun Liu
Substantial data from preclinical studies have revealed the biphasic effects of statins on cardiovascular angiogenesis. Although some have reported the anti-angiogenic potential of statins in malignant tumors, however, the underlying mechanism remains poorly understood. The aim of this study is to elucidate the mechanism by which simvastatin, a member of the statin family, inhibits tumor angiogenesis. Simvastatin significantly suppressed tumor cells-conditioned medium (TCM)-induced angiogenic promotion in vitro, and resulted in a dose-dependent anti-angiogenesis in vivo...
March 13, 2018: Cancer Science
Guang Ren, Agnes M Rimando, Suresh T Mathews
Pterostilbene, a bioactive component of blueberries and grapes, shows structural similarity to resveratrol, and exhibits antioxidant, anti-inflammatory, anti-cancer, hypoglycemic, and cholesterol lowering effects. Recent evidence indicates that pterostilbene is an agonist of the nuclear receptor, peroxisome proliferator-activated receptor-alpha (PPAR-α). Since PPAR-α agonists induce peroxisomal proliferation and fatty acid oxidation, we examined gene expression of acyl CoA oxidase (ACO) and carnitine palmitoyl transferase-1 (CPT-1)...
March 7, 2018: Biochemical and Biophysical Research Communications
Kentaro Oki, Edward B Arias, Makoto Kanzaki, Gregory D Cartee
5' AMP-activated protein kinase (AMPK) activation may be part of the exercise-induced process that enhances insulin sensitivity. Independent of exercise, acute prior treatment of skeletal muscles isolated from young rats with a pharmacological AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), causes subsequently improved insulin-stimulated glucose uptake (GU). However, efficacy of a single prior AICAR exposure on insulin-stimulated GU in muscles from old animals has not been studied...
March 8, 2018: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Songlin Liu, Yunhong Tang, Maomao Yan, Weixi Jiang
Breast cancer has been emerging as a most common threat among women, thus many efforts were made to find drugs for fighting breast cancer. So far, PI3K (Phosphatidylinositol-4,5-bisphosphate 3-kinase) inhibitors have been believed to be effective drugs until frequent resistance emerged. Recently, PI3K H1047R mutation has been reported to sensitize breast cancer cells to PI3K inhibition by aspirin. Considering aspirin activates AMPK (AMP-activated protein kinase) simultaneously, it is possible that AMPK activators and PI3K inhibitors can synergistically inhibit breast cancers...
March 5, 2018: Investigational New Drugs
Matharage S I De Silva, Adam W Dayton, Lance R Rhoten, John W Mallett, Jared C Reese, Mathieu D Squires, Andrew P Dalley, James P Porter, Allan M Judd
In bovine adrenal zona fasciculata (ZF) and NCI-H295R cells, interleukin-6 (IL-6) increases cortisol release, increases expression of steroidogenic acute regulatory protein (StAR), cholesterol side chain cleavage enzyme (P450scc), and steroidogenic factor 1 (SF-1) (increases steroidogenic proteins), and decreases the expression of adrenal hypoplasia congenita-like protein (DAX-1) (inhibits steroidogenic proteins). In contrast, IL-6 decreases bovine adrenal zona reticularis (ZR) androgen release, StAR, P450scc, and SF-1 expression, and increases DAX-1 expression...
March 1, 2018: Steroids
Chun Cao, Tao Gao, Yan Cheng, Minhua Cheng, Ting Su, Fengchan Xi, Cuili Wu, Wenkui Yu
Hypercatabolism plays a critical role in the pathogenesis of post-critical care debility in critical patients. Central nervous system may exerte a critical role in the regulation of hypercatabolism. However, little is known about the exact mechanisms of the central role. Here, we reported that actived hypothalamic AMP-activated protein kinase (AMPK)-induced autophagy modulated the expression of POMC to ameliorate hypercatabolism in septic rats. Firstly, rats were i.c.v. injected with the lentiviral vector containing shRNA against POMC...
February 26, 2018: Biochemical and Biophysical Research Communications
Florence Mailleux, Christophe Beauloye, Jean-Luc Balligand, Sandrine Horman, Luc Bertrand
Pathological cardiac hypertrophy, which is a compensatory mechanism established to maintain cardiac function in response to neurohormonal or mechanical stresses, becomes maladaptive with time and frequently leads to heart failure. AMP-activated protein kinase (AMPK) has been extensively described in the literature to act as a break in cardiac hypertrophy development. Its anti-hypertrophic action mostly correlates with the inhibition of several important players of cardiac hypertrophy including protein synthesis and pro-hypertrophic gene expression pathways involving the transcription factor nuclear factor of activated T cells (NFAT) and the mitogen-activated protein kinases ERK1/2...
2018: Methods in Molecular Biology
Xingping Qin, Haowen Qiao, Songlin Wu, Jing Cheng, Qi Wan, Renzhong Liu
Curcumin, a phenolic pigment, plays an inhibitory role in astrocytes activation, a key step for neuropathic pain (NP). The present study aimed to investigate the mechanism behind the therapeutic effect of Curcumin on NP in vitro. Specifically, we investigated the inhibitory effect of Curcumin on tumor necrosis factor-α (TNF-α)-induced astrocyte migration. We also studied the effects of Curcumin on monocyte chemoattractant protein-1(MCP-1) expression and activity, as well as super oxide dismutase-2 (SOD2) expression and activity in TNF-α-induced astrocytes...
February 19, 2018: Neurochemical Research
Ji-Qiang Liu, Li Zhang, Ji Yao, Shuo Yao, Ting Yuan
Chronic obstructive pulmonary disease (COPD), is characterized by inflammation of airways accompanied by a progressive destruction of lung parenchyma. This process is initiated in most cases by cigarette smoking. In this study we investigated the role of AMP activated protein kinase (AMPK) in cigarette smoke extract (CSE)-induced airway epithelial cell apoptosis as a consequence of endoplasmic reticulum stress (ER stress). Exposure of human bronchial epithelial cells (HBEpC) to CSE resulted in apoptosis as detected using Annexin V-PI flow cytometry...
February 12, 2018: Biochemical and Biophysical Research Communications
Xiaoxin Guo, Qi Jiang, Alessandra Tuccitto, Darren Chan, Samih Alqawlaq, Gah-Jone Won, Jeremy M Sivak
Neurons are highly sensitive to metabolic and oxidative injury, but endogenous astrocyte mechanisms have a critical capacity to provide protection from these stresses. We previously reported that the master regulator PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1α) is necessary for retinal astrocytes to mount effective injury responses, with particular regard to oxidative stress. Yet, this pathway has not been well studied in glia. PGC-1α is a transcriptional co-activator that is dysregulated in a variety of neurodegenerative diseases...
February 10, 2018: Neurobiology of Disease
Jannell V Bazurto, Stephen P Dearth, Eric D Tague, Shawn R Campagna, Diana M Downs
In Salmonella enterica, aminoimidazole carboxamide ribotide (AICAR) is a purine biosynthetic intermediate and a substrate of the AICAR transformylase/IMP cyclohydrolase (PurH) enzyme. When purH is eliminated in an otherwise wild-type strain, AICAR accumulates and indirectly inhibits synthesis of the essential coenzyme thiamine pyrophosphate (TPP). In this study, untargeted metabolomics approaches were used to i) corroborate previously defined metabolite changes, ii) define the global consequences of AICAR accumulation and iii) investigate the metabolic effects of mutations that restore thiamine prototrophy to a purH mutant...
November 22, 2017: Microbial Cell
Christin Riedinger, Michael Mendler, Andrea Schlotterer, Thomas Fleming, Jürgen Okun, Hans-Peter Hammes, Stephan Herzig, Peter P Nawroth
The enzyme AICAR-transformylase/IMP cyclohydrolase (ATIC) catalyzes the last two steps of purine de-novo synthesis. It metabolizes AICAR, which is an AMP analogue, leading to activation of AMPK. It was investigated whether the AICAR-ATIC pathway plays a role in the high glucose (HG) mediated DNA damage response and AICAR mediated AMPK activation, explaining the detrimental effects of glucose on neuronal damages and shortening of lifespan. HG up-regulated the expression and activity of Caenorhabditis elegans homologue of ATIC, C55F2...
February 2, 2018: Journal of Biological Chemistry
Xiaoting Li, Lu Yu, Jing Gao, Xukun Bi, Juhong Zhang, Shiming Xu, Meihui Wang, Mengmeng Chen, Fuyu Qiu, Guosheng Fu
Diabetes Mellitus is a common disorder, with increasing risk of cardiac arrhythmias. Studies have shown that altered connexin expression and gap junction remodeling under hyperglycemia contribute to the high prevalence of cardiac arrhythmias and even sudden death. Connexin 43 (Cx43), a major protein that assembles to form cardiac gap junctions, has been found to be downregulated under high glucose conditions, along with inhibition of gap junctional intercellular communication (GJIC). While, apelin, a beneficial adipokine, increases Cx43 protein expression in mouse and human embryonic stem cells during cardiac differentiation...
February 2018: Aging and Disease
Nobuhiko Itami, Koumei Shirasuna, Takehito Kuwayama, Hisataka Iwata
Low oocyte quality is a possible causal factor of obesity-induced infertility. High palmitic acid (PA) concentration in follicular fluid is a crucial feature noted in obese women. The present study examined how high PA concentration reduced mitochondrial quality in oocytes and investigated a possible countermeasure against mitochondrial dysfunction. Cumulus cell-oocyte complexes (COCs) were obtained from the ovaries of gilts, and incubated in medium containing PA (0.5 mM) or vehicle (BSA) for 44 h. Culturing oocytes at high PA concentration induced mitochondrial dysfunction determined by high ROS and low ATP content in oocytes...
January 29, 2018: Biology of Reproduction
Santosh Karnewar, Praveen Kumar Neeli, Devayani Panuganti, Sasikumar Kotagiri, Sreevidya Mallappa, Nishant Jain, Mahesh Kumar Jerald, Srigiridhar Kotamraju
Endothelial senescence in conjunction with mitochondrial dysfunction orchestrates age-associated cardiovascular disorders. In this study we investigated the causal link between these two processes and studied the molecular mechanisms by which metformin acts to coordinate the delay of endothelial senescence via enhancing mitochondrial biogenesis/function. AMPK activators metformin and AICAR delayed endothelial senescence via SIRT1-mediated upregulation of DOT1L, leading to increased trimethylation of H3K79 (H3K79me3)...
January 20, 2018: Biochimica et Biophysica Acta
Rugina I Neuman, Juliette A M van Kalmthout, Daniel J Pfau, Dhariyat M Menendez, Lawrence H Young, John N Forrest
The production of endogenous adenosine during secretagogue stimulation of CFTR leads to feedback inhibition limiting further chloride secretion in the rectal gland of the dogfish shark (Squalus acanthias). In the present study, we examined the role of AMP-kinase (AMPK) as an energy sensor also modulating chloride secretion through CFTR. We found that glands perfused with forskolin and isobutylmethylxanthine (F + I), potent stimulators of chloride secretion in this ancient model, caused significant phosphorylation of the catalytic subunit Thr172 of AMPK...
December 20, 2017: American Journal of Physiology. Cell Physiology
Ryo Iwaoka, Kohsuke Kataoka
Insulin mRNA expression in pancreatic islet β-cells is upregulated by extracellular glucose concentration, but the underlying mechanism remains incompletely understood. MafA is a transcriptional activator specifically enriched in β-cells that binds to the insulin gene promoter. Its expression is transcriptionally and post-transcriptionally regulated by glucose. Moreover, AMP-activated protein kinase (AMPK), a regulator of cellular energy homeostasis, is inhibited by high glucose, and this inhibition is essential for the up-regulation of insulin gene expression and glucose-stimulated insulin secretion (GSIS)...
January 18, 2018: Journal of Biological Chemistry
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