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AmpK AND lactic acid

Hongbao Guo, Yang Nan, Yingwei Zhen, Yahui Zhang, Liyun Guo, Kai Yu, Qiang Huang, Yue Zhong
MicroRNAs play an important role in tumor development and progression. Tumor growth is closely associated with glucose metabolism. Specifically, tumor cells produce energy (ATP) under aerobic and anaerobic conditions through glycolysis and metabolites, such as lactic acid and ATP, as a result of the Warburg effect. However, the transport of glucose into cells depends on protein transporters in the cell membrane. Therefore, this area has recently become a topic of interest for research on targeted cancer therapy...
July 31, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Zhixin Xu, Erchao Li, Chang Xu, Lei Gan, Jian G Qin, Liqiao Chen
Adenosine monophosphate-activated protein kinase (AMPK) is a prevalent mammalian energy metabolism sensor, but little is known about its role as an energy sensor in fish experiencing stress. We aimed to study AMPK in Oreochromis niloticus on both the molecular and the physical level. We found that the cDNAs encoding the AMPKα1 and AMPKα2 variants of the O. niloticus catalytic α subunit were 1753bp and 2563 bp long and encoded 571 and 557 amino acids, respectively. Both the AMPKα1 and the AMPKα2 isoform possess structural features similar to mammalian AMPKα, including a phosphorylation site at Thr172 in the N-terminus, and exhibit high homology with other fish and vertebrate AMPKα sequences (81...
August 2016: Aquatic Toxicology
Neetu Saini, Rupinder Kaur Sodhi, Lotika Bajaj, Ravi Shankar Pandey, Upendra Kumar Jain, Om Prakash Katare, Jitender Madan
BACKGROUND AND OBJECTIVE: Metformin hydrochloride (MTF-HCl) is extensively recommended by physicians for the treatment of polycystic ovary syndrome (PCOS). Mechanistically, MTF-HCl activates AMP-dependent kinase-α (AMPK-α) pathway to decrease the glucose production, enhances fatty acid oxidation and elevates the uptake of glucose in tissues. However, despite favourable physicochemical properties, oral administration of MTF-HCl is associated with impaired bioavailability (50-60%), lactic-acidosis and frequent dosing (500mg 2-3 times a day) in PCOS that ultimately influence the patient compliance...
August 1, 2016: Colloids and Surfaces. B, Biointerfaces
Francesco Massari, Chiara Ciccarese, Matteo Santoni, Roberto Iacovelli, Roberta Mazzucchelli, Francesco Piva, Marina Scarpelli, Rossana Berardi, Giampaolo Tortora, Antonio Lopez-Beltran, Liang Cheng, Rodolfo Montironi
Metabolism of bladder cancer represents a key issue for cancer research. Several metabolic altered pathways are involved in bladder tumorigenesis, representing therefore interesting targets for therapy. Tumor cells, including urothelial cancer cells, rely on a peculiar shift to aerobic glycolysis-dependent metabolism (the Warburg-effect) as the main energy source to sustain their uncontrolled growth and proliferation. Therefore, the high glycolytic flux depends on the overexpression of glycolysis-related genes (SRC-3, glucose transporter type 1 [GLUT1], GLUT3, lactic dehydrogenase A [LDHA], LDHB, hexokinase 1 [HK1], HK2, pyruvate kinase type M [PKM], and hypoxia-inducible factor 1-alpha [HIF-1α]), resulting in an overproduction of pyruvate, alanine and lactate...
April 2016: Cancer Treatment Reviews
Jie Dai, Ling Lin, Dan Zhou, Qing Ai, Pu Ge, Li Zhang
AMP activated protein kinase (AMPK) is a pivotal metabolic regulatory enzyme and novel target of controlling inflammation. Our previous studies had demonstrated that 5-amino-4-imidazolecarboxamide riboside (AICAR), an AMPK activator, attenuated lipopolysaccharide (LPS)/D-galactosamine (D-gal)-induced fulminant hepatitis via suppressing inflammatory response. Since inflammation usually activates the coagulation response and aggravates inflammation-induced tissue injury, the present study was to explore the effects of AICAR on inflammation-induced activation of coagulation...
February 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Mei Peng, Qiongli Su, Qing Zeng, Le Li, Zhihong Liu, Lei Xue, Yan Cheng, Yanjun Huang, Ting Tao, Hongwei Lv, Xiaohui Li, Xiaojun Tao, Peng Guo, Alex F Chen, Xiaoping Yang
Anticancer potential of metformin has been extensively studied. However, its anticancer clinical use remains yet to be approved since sufficient concentration on target organs could not be achieved via conventional administration. To overcome this drawback, we aim to examine the efficiency of novel intravesical treatment of metformin on syngeneic orthotopic preclinical model. Three human and one murine bladder cancer cell lines were tested in vitro for inhibitory sensitivity by MTT and cologenic assays. AMPK pathway including AKT, Erk and S6K was examined by western blot and further explored by regulating activated levels using specific inhibitors...
February 23, 2016: Oncotarget
Ana Martínez-Zamora, Salvador Meseguer, Juan M Esteve, Magda Villarroya, Carmen Aguado, J Antonio Enríquez, Erwin Knecht, M-Eugenia Armengod
GTPBP3 is an evolutionary conserved protein presumably involved in mitochondrial tRNA (mt-tRNA) modification. In humans, GTPBP3 mutations cause hypertrophic cardiomyopathy with lactic acidosis, and have been associated with a defect in mitochondrial translation, yet the pathomechanism remains unclear. Here we use a GTPBP3 stable-silencing model (shGTPBP3 cells) for a further characterization of the phenotype conferred by the GTPBP3 defect. We experimentally show for the first time that GTPBP3 depletion is associated with an mt-tRNA hypomodification status, as mt-tRNAs from shGTPBP3 cells were more sensitive to digestion by angiogenin than tRNAs from control cells...
2015: PloS One
Jiyun Lee, Gayeung Kwon, Young-Hee Lim
The mechanism whereby lactic acid bacteria extend the lifespan of Caenorhabditis elegans has previously been elucidated. However, the role of Weissella species has yet not been studied. We show that Weissella koreensis and Weissella cibaria significantly (p < 0.05) extend the lifespan of C. elegans compared with Escherichia coli OP50 and induce the expression of several genes related to lifespan extension (daf-16, aak-2, jnk-1, sod-3 and hif-1). Oral administration of Weissella altered reactive oxygen species (ROS) production and lowered the accumulation of lipofuscin and increased locomotor activity (which translates to a delay in ageing)...
2015: Scientific Reports
Kazuya Toda, Shogo Takeda, Shoketsu Hitoe, Seikou Nakamura, Hisashi Matsuda, Hiroshi Shimoda
Enhancement of muscular energy production is thought to improve locomotive functions and prevent metabolic syndromes including diabetes and lipidemia. Black ginger (Kaempferia parviflora) has been cultivated for traditional medicine in Thailand. Recent studies have shown that black ginger extract (KPE) activated brown adipocytes and lipolysis in white adipose tissue, which may cure obesity-related dysfunction of lipid metabolism. However, the effect of KPE on glucose and lipid utilization in muscle cells has not been examined yet...
April 2016: Journal of Natural Medicines
Jingjing Song, Yingwu Wang, Meiyu Teng, Guangsheng Cai, Hongkai Xu, Hanxiao Guo, Yang Liu, Di Wang, Lesheng Teng
Cordyceps militaris has been used extensively as a crude drug and a folk tonic food in East Asia due to its various pharmacological activities. Our study aims to investigate the effect of Cordyceps militaris fruit body extract (CM) on antifatigue in mouse model. Two week CM administration significantly delayed fatigue phenomenon which is confirmed via rotating rod test, forced swimming test and forced running test. Compared to nontreated mouse, CM administration increased ATP levels and antioxidative enzymes activity and reduced the levels of lactic acid, lactic dehydrogenase, malondialdehyde, and reactive oxygen species...
2015: Evidence-based Complementary and Alternative Medicine: ECAM
Tong Xing, Xinglian Xu, Nannan Jiang, ShaoLin Deng
The aim of this study was to determine the effects of pre-slaughter transport during summer and subsequent water shower spray on stress, postmortem glycolysis, energy metabolism and adenosine monophosphate-activated protein kinase (AMPK) in Pectoralis major (PM) muscle of broilers. Results indicated that transport during high ambient temperature induced the release of plasma corticosterone, which significantly affected stress conditions. Moreover, we found a lower energy status in the early postmortem period compared to the control group...
February 2016: Animal Science Journal, Nihon Chikusan Gakkaihō
Joffrey Pelletier, Danièle Roux, Benoit Viollet, Nathalie M Mazure, Jacques Pouysségur
Lactic acid generated by highly glycolytic tumours is exported by the MonoCarboxylate Transporters, MCT1 and MCT4, to maintain pHi and energy homeostasis. We report that MCT1 inhibition combined with Mct4 gene disruption severely reduced glycolysis and tumour growth without affecting ATP levels. Because of the key role of the 5'-AMP-activated protein kinase (AMPK) in energy homeostasis, we hypothesized that targeting glycolysis (MCT-blockade) in AMPK-null (Ampk(-/-)) cells should kill tumour cells from 'ATP crisis'...
May 20, 2015: Oncotarget
Akio Ohta, Yasushi Tanaka
Metformin, a biguanide, is considered in EASD and ADA to be a first-line glucose-lowering agent for patients with type 2 diabetes. The effectiveness of metformin as an anti-diabetic drug is explained by its ability to lower blood glucose by decreasing hepatic glucose production, stimulating glucose uptake in the muscle, and increasing fatty acid oxidation in adipose tissue. The exact mechanism of this effect has not been fully understood, but metformin is thought to activate hepatic AMP-activated protein kinase (AMPK), and it suppresses liver glucagon signal by increasing AMP due to inhibition of mitochondrial respiratory complex I...
March 2015: Nihon Rinsho. Japanese Journal of Clinical Medicine
Baoping Jiang, Liang Le, Huimin Pan, Keping Hu, Lijia Xu, Peigen Xiao
Dihydromyricetin (DMY), the major bioactive flavonoid ingredient extracted from the leaves of Ampelopsis grossedentata (Hand.-Mazz) W.T. Wang, displays multiple pharmacological activities, including oxidation resistance, antitumor properties and free radical scavenging capacities. However, the role of DMY in methylglyoxal (MG)-induced diabetes-associated cognitive decline and its underlying molecular mechanisms are unclear. The aim of the present study was to evaluate the effects of DMY on oxidative stress and glucose transport activity in a MG-induced PC12 cell line and to explore the related mechanisms...
October 2014: Brain Research Bulletin
Xin Xie, Xiao-Ming Xu, Na Li, Yong-Hui Zhang, Yu Zhao, Chun-Yan Ma, De-Li Dong
DMH1(4-[6-(4-Isopropoxyphenyl)pyrazolo [1,5-a]pyrimidin-3-yl] quinoline) is a compound C analogue with the structural modifications at the 3- and 6-positions in pyrazolo[1,5-a]pyrimidine backbone. Compound C was reported to inhibit both AMPK and Akt. Our preliminary work found that DMH1 activated Akt. Since Akt was involved in glucose metabolism, we aimed to identify the effects of DMH1 on glucose metabolism in L6 rat muscle cells and the potential mechanism. Results showed that DMH1 increased lactic acid release and glucose consumption in L6 rat muscle cells in a dose-dependent manner...
2014: PloS One
Xiu-Xiu Wang, Pu-Hong He, Ming-Guang Feng, Sheng-Hua Ying
SNF1/AMPK protein kinase plays important roles in fungal development and activation of catabolite-repressed genes. In this study, we characterized the role of the Beauveria bassiana SNF1 ortholog. The vegetative growth of the ΔBbSNF1 mutant was reduced by 16 to 50 % on diverse carbon/nitrogen sources. Transcriptional analysis revealed a collection of proteases and chitinases that were not induced when the mutant was grown on complex carbon/nitrogen sources. BbSNF1 also contributes to extracellular acidification...
October 2014: Applied Microbiology and Biotechnology
Keisuke Sawada, Yoko Yamashita, Tianshun Zhang, Kaku Nakagawa, Hitoshi Ashida
The present study demonstrates that glabridin, a prenylated isoflavone in licorice, stimulates glucose uptake through the adenosine monophosphate-activated protein kinase (AMPK) pathway in L6 myotubes. Treatment with glabridin for 4h induced glucose uptake in a dose-dependent manner accompanied by the translocation of glucose transporter type 4 (GLUT4) to the plasma membrane. Glabridin needed at least 4h to increase glucose uptake, while it significantly decreased glycogen and increased lactic acid within 15 min...
August 5, 2014: Molecular and Cellular Endocrinology
Teresa Valero
Organelle biogenesis is concomitant to organelle inheritance during cell division. It is necessary that organelles double their size and divide to give rise to two identical daughter cells. Mitochondrial biogenesis occurs by growth and division of pre-existing organelles and is temporally coordinated with cell cycle events [1]. However, mitochondrial biogenesis is not only produced in association with cell division. It can be produced in response to an oxidative stimulus, to an increase in the energy requirements of the cells, to exercise training, to electrical stimulation, to hormones, during development, in certain mitochondrial diseases, etc...
2014: Current Pharmaceutical Design
Harvey J Grill
No abstract text is available yet for this article.
April 1, 2014: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Andrew J R Cochran, Michael E Percival, Steven Tricarico, Jonathan P Little, Naomi Cermak, Jenna B Gillen, Mark A Tarnopolsky, Martin J Gibala
High-intensity interval training (HIIT) performed in an 'all-out' manner (e.g. repeated Wingate tests) is a time-efficient strategy to induce skeletal muscle remodelling towards a more oxidative phenotype. A fundamental question that remains unclear, however, is whether the intermittent or 'pulsed' nature of the stimulus is critical to the adaptive response. In study 1, we examined whether the activation of signalling cascades linked to mitochondrial biogenesis was dependent on the manner in which an acute high-intensity exercise stimulus was applied...
May 1, 2014: Experimental Physiology
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