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https://www.readbyqxmd.com/read/29120354/trans-plasma-membrane-electron-transport-and-ascorbate-efflux-by-skeletal-muscle
#1
Amanda M Eccardt, Thomas P Bell, Lyn Mattathil, Rohan Prasad, Shannon C Kelly, Jonathan S Fisher
Trans-plasma membrane electron transport (tPMET) and the antioxidant roles of ascorbate reportedly play a role in protection of cells from damage by reactive oxygen species, which have been implicated in causing metabolic dysfunction such as insulin resistance. Skeletal muscle comprises the largest whole-body organ fraction suggesting a potential role of tPMET and ascorbate export as a major source of extracellular antioxidant. We hypothesized that skeletal muscle is capable of tPMET and ascorbate efflux. To measure these processes, we assayed the ability of cultured muscle cells, satellite cells, and isolated extensor digitorum longus (EDL) and soleus (SOL) to reduce two extracellular electron acceptors, water soluble tetrazolium salt 1 (WST-1), and dichlorophenolindophenol (DPIP)...
November 9, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29117108/effect-of-aicar-and-5-fluorouracil-on-x-ray-repair-cross-complementing-group-1-expression-and-consequent-cytotoxicity-regulation-in-human-hct-116-colorectal-cancer-cells
#2
Ko-Chao Lee, Chien-Tsong Lin, Shun-Fu Chang, Cheng-Nan Chen, Jing-Lan Liu, Wen-Shih Huang
Colorectal cancer (CRC) is one of the leading causes of cancer mortality and 5-Fluorouracil (5-FU) is the most common chemotherapy agent of CRC. A high level of X-ray repair cross complementing group 1 (XRCC1) in cancer cells has been associated with the drug resistance occurrence. Moreover, the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) has been indicated to regulate the cancer cell survival. Thus, this study was aimed to examine whether XRCC1 plays a role in the 5-FU/AMPK agonist (AICAR)-induced cytotoxic effect on CRC and the underlying mechanisms...
November 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29115402/ampk-activation-serves-a-critical-role-in-mitochondria-quality-control-via-modulating-mitophagy-in-the-heart-under-chronic-hypoxia
#3
Huagang Zhang, Bo Liu, Tianbo Li, Yun Zhu, Guiping Luo, Yunhan Jiang, Fuqin Tang, Zhao Jian, Yingbin Xiao
Mitochondrial biogenesis is one of the generally accepted regulatory mechanisms in the heart under chronic hypoxia. The precise quantity and quality control of mitochondria is critical for the survival and function of cardiomyocytes. Mitochondrial autophagy, also known as mitophagy, which selectively eliminates dysfunctional and unwanted mitochondria, is the most important type of mitochondrial quality control. However, the detailed molecular mechanisms of mitophagy in cardiomyocytes have been largely undefined...
October 26, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29089333/electrical-pulse-stimulation-induces-glut4-glucose-transporter-translocation-in-c2c12-myotubes-that-depends-on-rab8a-rab13-and-rab14
#4
Zhu Li, Yingying Yue, Fang Hu, Chang Zhang, Xiaofang Ma, Nana Li, Lihong Qiu, Maolong Fu, Liming Chen, Zhi Yao, Philip J Bilan, Amira Klip, Wenyan Niu
The signals mobilizing GLUT4 to the plasma membrane in response to muscle contraction are less known than those elicited by insulin. This disparity is undoubtedly due to lack of suitable in vitro models to study skeletal muscle contraction. We generated C2C12 myotubes stably expressing HA-tagged GLUT4 (C2C12-GLUT4HA) that contract in response to electrical pulse stimulation (EPS) and investigated molecular mechanisms regulating GLUT4HA EPS (60min, 20V, 1Hz, 24ms pulses at 976ms intervals) elicited a gain in surface GLUT4HA (GLUT4 translocation) comparably to insulin or 5-amino imidazole-4-carboxamide ribonucleotide (AICAR)...
October 31, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29063699/characterization-of-aicar-transformylase-imp-cyclohydrolase-atic-from-staphylococcus-lugdunensis
#5
Preeti Verma, Bibekananda Kar, Ritu Varshney, Partha Roy, Ashwani K Sharma
The 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase/inosine monophosphate (IMP) cyclohydrolase (ATIC) catalyzes final two steps of purine nucleotide de novo biosynthetic pathway. The present study reports the characterization of ATIC from Staphylococcus lugdunensis (SlugATIC). Apart from kinetic analysis and a detailed biophysical characterization of SlugATIC, the role of ATIC in cell proliferation has been demonstrated for the first time. The purified recombinant SlugATIC and its truncated domains exists mainly in dimeric form was revealed in gel filtration and glutaraldehyde cross linking studies...
October 24, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29048631/autophagy-induction-enhances-tetrandrine-induced-apoptosis-via-the-ampk-mtor-pathway-in-human-bladder-cancer-cells
#6
Bo Kou, Wei Liu, Xu Xu, Yang Yang, Qiuyue Yi, Fengwei Guo, Jianpeng Li, Jinsong Zhou, Qingshan Kou
Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the roots of Stephania tetrandra is a traditional Chinese medicine and exerts anticancer capacity in various types of cancers. Previous studies have shown that tetrandrine induces apoptosis in bladder cancer cells via activation of the caspase cascade. However, the underlying mechanism has not yet been reported. Autophagy is a cellular process involved in the degradation of broken proteins and aging organelles to maintain homeostasis. Recent studies indicate that autophagy is implicated in cancer therapy...
September 21, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29032594/implementation-of-aicar-analysis-by-gc-c-irms-for-anti-doping-purposes
#7
C Buisson, C Frelat, C Mongongu, N Martinat, M Audran
AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside), is a naturally-occurring substance which is part to the prohibited list of WADA. It is claimed to improve physical performance when administered as a supplement. As for other endogenous compounds such as steroids, the GC-C-IRMS analysis remains an efficient tool to differentiate endogenous substances from exogenous ones. A protocol was described in the literature for the analysis of AICAR by GC-C-IRMS. The aim of the present study was to implement this protocol in our laboratory and to propose solutions to avoid the difficulties encountered...
October 15, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/29025860/negative-regulation-of-trpa1-by-amp-activated-protein-kinase-in-primary-sensory-neurons-as-a-potential-mechanism-of-painful-diabetic-neuropathy
#8
Shenglan Wang, Kimiko Kobayashi, Yoko Kogure, Hiroki Yamanaka, Satoshi Yamamoto, Hideshi Yagi, Koichi Noguchi, Yi Dai
AMP activated protein kinase (AMPK) is a widely expressed intracellular energy sensor that monitors and modulates energy expenditure. Transient receptor potential ankyrin 1 (TRPA1) channel is a widely recognized chemical and thermal sensor that plays vital roles in pain transduction. Here, we discovered a functional link between AMPK and TRPA1 in dorsal root ganglion (DRG) neurons, in which AMPK activation rapidly resulted in downregulation of membrane-associated TRPA1 and its channel activity within minutes...
October 12, 2017: Diabetes
https://www.readbyqxmd.com/read/29022062/fak-tyrosine-phosphorylation-is-regulated-by-ampk-and-controls-metabolism-in-human-skeletal-muscle
#9
David G Lassiter, Carolina Nylén, Rasmus J O Sjögren, Alexander V Chibalin, Harriet Wallberg-Henriksson, Erik Näslund, Anna Krook, Juleen R Zierath
AIMS/HYPOTHESIS: Insulin-mediated signals and AMP-activated protein kinase (AMPK)-mediated signals are activated in response to physiological conditions that represent energy abundance and shortage, respectively. Focal adhesion kinase (FAK) is implicated in insulin signalling and cancer progression in various non-muscle cell types and plays a regulatory role during skeletal muscle differentiation. The role of FAK in skeletal muscle in relation to insulin stimulation or AMPK activation is unknown...
October 11, 2017: Diabetologia
https://www.readbyqxmd.com/read/29021780/chronic-5-aminoimidazole-4-carboxamide-1-%C3%AE-d-ribofuranoside-treatment-induces-phenotypic-changes-in-skeletal-muscle-but-does-not-improve-disease-outcomes-in-the-r6-2-mouse-model-of-huntington-s-disease
#10
Marie-France Paré, Bernard J Jasmin
Huntington's disease (HD) is an autosomal dominant neurodegenerative genetic disorder characterized by motor, cognitive, and psychiatric symptoms. It is well established that regular physical activity supports brain health, benefiting cognitive function, mental health as well as brain structure and plasticity. Exercise mimetics (EMs) are a group of drugs and small molecules that target signaling pathways in skeletal muscle known to be activated by endurance exercise. The EM 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) has been shown to induce cognitive benefits in healthy mice...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28988114/regulatory-effects-of-the-ampk%C3%AE-sirt1-molecular-pathway-on-insulin-resistance-in-pcos-mice-an-in%C3%A2-vitro-and-in%C3%A2-vivo-study
#11
Xin Tao, Lei Chen, Lisi Cai, Shuqi Ge, Xuanying Deng
In order to preliminarily explore the correlation between the AMPKα-SIRT1 pathway and insulin resistance and reproductive function in PCOS mice and find the pathogenesis molecular mechanism and potential therapeutic target of PCOS, we carried out in vitro study of human granulosa KGN cells and in vivo study of PCOS mouse model which was constructed with DHEA, and AICAR and Compound C were applied. We have found that SIRT1 and AMPKα expression in KGN cells gradually decreased as DHEA concentration increased; Mice of the PCOS model were in an obvious status of IR (P < 0...
October 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28978086/ampk-activation-dependent-autophagy-compromises-oleanolic-acid-induced-cytotoxicity-in-human-bladder-cancer-cells
#12
Yarong Song, Peng Zhang, Yadong Sun, Xuechao Li, Lifeng Chen, Yajun Xiao, Yifei Xing
Autophagy is an evolutionarily conserved catabolic process in eukaryotic cells, which allows cells to overcome a wide array of of stresses and has recently been shown to result in drug resistance. This study examined the effect of autophagy on oleanolic acid (OA)-induced cytotoxicity against bladder cancer cells. Our study demonstrated that OA inhibited cell viability, proliferation, and induced apoptosis in bladder cancer lines T24 and EJ. Furthermore, OA induced autophagy in both cell lines by activating AMP-activated protein kinase (AMPK), inhibiting mechanistic target of rapamycin (mTOR) and promoting unc-51 like autophagy activating kinase 1 (ULK1)...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28975644/rapid-decline-in-myhc-i-%C3%AE-mrna-expression-in-rat-soleus-during-hindlimb-unloading-is-associated-with-the-ampk-dephosphorylation
#13
Natalia A Vilchinskaya, Ekaterina P Mochalova, Tatiana L Nemirovskaya, Timur M Mirzoev, Olga V Turtikova, Boris S Shenkman
One of the key events that occurs during skeletal muscle inactivation is a change in myosin phenotype, i.e. increased expression of fast isoforms and decreased expression of slow isoform of myosin heavy chain (MyHC). It is known that calcineurin/NFAT and AMP-activated protein kinase (AMPK) can regulate the expression of genes encoding MyHC slow isoform. Earlier, we found a significant decrease in phosphorylated AMPK in rat soleus after 24 h of hindlimb unloading (HU). We hypothesized that a decrease in AMPK phosphorylation and subsequent histone deacetylase (HDAC) nuclear translocation can be one of the triggering events leading to a reduced expression of slow MyHC...
October 3, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28975042/5-aminoimidazole-4-carboxamide-ribonucleoside-induced-autophagy-flux-during-differentiation-of-monocytic-leukemia-cells
#14
Vilma Dembitz, Hrvoje Lalic, Dora Visnjic
Pharmacological modulators of AMP-dependent kinase (AMPK) have been suggested in treatment of cancer. The biguanide metformin and 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) have been reported to inhibit proliferation of solid tumors and hematological malignancies, but their role in differentiation is less explored. Our previous study demonstrated that AICAR alone induced AMPK-independent expression of differentiation markers in monocytic U937 leukemia cells, and no such effects were observed in response to metformin...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28974562/autophagy-and-mitochondrial-biogenesis-impairment-contributes-to-age-dependent-liver-injury-in-experimental-sepsis-dysregulation-of-amp-activated-protein-kinase-pathway
#15
Yu Inata, Satoshi Kikuchi, Ravi S Samraj, Paul W Hake, Michael O'Connor, John R Ledford, James O'Connor, Patrick Lahni, Vivian Wolfe, Giovanna Piraino, Basilia Zingarelli
Age is an independent risk factor of multiple organ failure in patients with sepsis. However, the age-related mechanisms of injury are not known. AMPK is a crucial regulator of energy homeostasis, which controls mitochondrial biogenesis by activation of peroxisome proliferator-activated receptor-γ coactivator-α (PGC-1α) and disposal of defective organelles by autophagy. We investigated whether AMPK dysregulation might contribute to age-dependent liver injury in young (2-3 mo) and mature male mice (11-13 mo) subjected to sepsis...
October 3, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28962017/treatment-with-aicar-inhibits-blastocyst-development-trophectoderm-differentiation-and-tight-junction-formation-and-function-in-mice
#16
Michele D Calder, Nicole A Edwards, Dean H Betts, Andrew J Watson
STUDY QUESTION: What is the impact of adenosine monophosphate-activated protein kinase (AMPK) activation on blastocyst formation, gene expression, and tight junction formation and function? SUMMARY ANSWER: AMPK activity must be tightly controlled for normal preimplantation development and blastocyst formation to occur. WHAT IS KNOWN ALREADY: AMPK isoforms are detectable in oocytes, cumulus cells and preimplantation embryos. Cultured embryos are subject to many stresses that can activate AMPK...
November 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28955248/aicar-administration-attenuates-hemorrhagic-hyperglycemia-and-lowers-oxygen-debt-in-anesthetized-male-rabbits
#17
Yi Huang, Paul H Ratz, Amy S Miner, Victoria A Locke, Grace Chen, Yang Chen, Robert W Barbee
Background: Many strategies have been utilized to treat traumatic shock via improved oxygen delivery (DO2), while fewer have been used to in an attempt to reduce oxygen demand (VO2). The cellular energy sensor 5' adenosine monophosphate-activated protein kinase (AMPK) has the potential to modulate both whole-body DO2 and VO2. Therefore, we determined the effect of the AMPK activator AICAR (5-aminoimidazole-4-carboxamide 1-β-D-ribonucleoside) given acutely or chronically on key metabolites, hemodynamics, and oxygen consumption/delivery before and during hemorrhage in anesthetized male rabbits...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28952262/-piperine-regulates-glucose-metabolism-disorder-in-hepg2-cells-of-insulin-resistance-models-via-targeting-upstream-target-of-ampk-signaling-pathway
#18
Chun-Ping Wan, Ya-Gai Wei, Xiao-Xue Li, Li-Jun Zhang, Rui Yang, Zhao-Ri-Ge-Tu Bao
To investigate the effect of piperine on the disorder of glucose metabolism in the cell model with insulin resistance (IR) and explore the molecules mechanism on intervening the upstream target of AMPK signaling pathway. The insulin resistance models in HepG2 cells were established by fat emulsion stimulation. Then glucose consumption in culture supernatant was detected by GOD-POD method. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of leptin(LEP) and adiponectin(APN) in culture supernatant; Real-time quantitative PCR was used to assess the mRNA expression of APN and LEP; and the protein expression levels of LepR, AdipoR1, AdipoR2 and the activation of AMPK signaling pathway were detected by Western blot analysis...
February 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28943473/h2s-is-a-key-antisecretory-molecule-against-cholera-toxin-induced-diarrhoea-in-mice-evidence-for-non-involvement-of-the-ac-camp-pka-pathway-and-ampk
#19
Francisca B M Sousa, Luan K M Souza, Nayara A Sousa, Thiago S L Araújo, Simone de Araújo, Dvison M Pacífico, Irismara S Silva, Renan O Silva, Lucas A D Nicolau, Fabiana M Souza, Marcelo C Filgueiras, Jefferson S Oliveira, Marcellus H L P Souza, Jand Venes R Medeiros
Hydrogen sulphide (H2S) is a gasotransmitter that participates in various physiological and pathophysiological processes within the gastrointestinal tract. We studied the effects and possible mechanism of action of H2S in secretory diarrhoea caused by cholera toxin (CT). The possible mechanisms of action of H2S were investigated using an intestinal fluid secretion model in isolated intestinal loops on anaesthetized mice treated with CT. NaHS and Lawesson's reagent and l-cysteine showed antisecretory activity through reduction of intestinal fluid secretion and loss of Cl(-) induced by CT...
September 21, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28938894/in-vitro-progesterone-production-by-luteinized-human-mural-granulosa-cells-is-modulated-by-activation-of-ampk-and-cause-of-infertility
#20
E C Bowdridge, M W Vernon, J A Flores, M J Clemmer
BACKGROUND: Mural granulosa cells from IVF patients were provided by the West Virginia University Center for Reproductive Medicine in Morgantown, WV. The effect of adenosine monophosphate activated protein kinase (AMPK) activation, primary cause of infertility, age, BMI, and pregnancy outcome on production of progesterone were examined separately. METHODS: Isolated mural sheets from IVF patients (n = 26) were centrifuged, supernatant discarded, and the pellet re-suspended in 500 μl of DMEM/F12...
September 22, 2017: Reproductive Biology and Endocrinology: RB&E
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