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Hexokinase 2

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https://www.readbyqxmd.com/read/27907091/real-time-fluorescence-measurements-of-ros-and-ca2-in-ischemic-reperfused-rat-hearts-detectable-increases-occur-only-after-mitochondrial-pore-opening-and-are-attenuated-by-ischemic-preconditioning
#1
Tatyana Andrienko, Philippe Pasdois, Andreas Rossbach, Andrew P Halestrap
Mitochondrial permeability transition pore (mPTP) opening is critical for ischemia / reperfusion (I/R) injury and is associated with increased [Ca2+] and reactive oxygen species (ROS). Here we employ surface fluorescence to establish the temporal sequence of these events in beating perfused hearts subject to global I/R. A bespoke fluorimeter was used to synchronously monitor surface fluorescence and reflectance of Langendorff-perfused rat hearts at multiple wavelengths, with simultaneous measurements of hemodynamic function...
2016: PloS One
https://www.readbyqxmd.com/read/27906079/muscle-specific-loss-of-bmal1-leads-to-disrupted-tissue-glucose-metabolism-and-systemic-glucose-homeostasis
#2
Brianna D Harfmann, Elizabeth A Schroder, Maureen T Kachman, Brian A Hodge, Xiping Zhang, Karyn A Esser
BACKGROUND: Diabetes is the seventh leading cause of death in the USA, and disruption of circadian rhythms is gaining recognition as a contributing factor to disease prevalence. This disease is characterized by hyperglycemia and glucose intolerance and symptoms caused by failure to produce and/or respond to insulin. The skeletal muscle is a key insulin-sensitive metabolic tissue, taking up ~80 % of postprandial glucose. To address the role of the skeletal muscle molecular clock to insulin sensitivity and glucose tolerance, we generated an inducible skeletal muscle-specific Bmal1 (-/-) mouse (iMSBmal1 (-/-))...
March 30, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27866313/two-myb-related-transcription-factors-play-opposite-roles-in-sugar-signaling-in-arabidopsis
#3
Yi-Shih Chen, Yi-Chi Chao, Tzu-Wei Tseng, Chun-Kai Huang, Pei-Ching Lo, Chung-An Lu
Sugar regulation of gene expression has profound effects at all stages of the plant life cycle. Although regulation at the transcriptional level is one of the most prominent mechanisms by which gene expression is regulated, only a few transcription factors have been identified and demonstrated to be involved in the regulation of sugar-regulated gene expression. OsMYBS1, an R1/2-type MYB transcription factor, has been demonstrated to be involved in sugar- and hormone-regulated α-amylase gene expression in rice...
November 19, 2016: Plant Molecular Biology
https://www.readbyqxmd.com/read/27856557/activating-transcription-factor-3-attenuates-chemokine-and-cytokine-expression-in-mouse-skeletal-muscle-after-exercise-and-facilitates-molecular-adaptation-to-endurance-training
#4
Rodrigo Fernández-Verdejo, Aline M Vanwynsberghe, Ahmed Essaghir, Jean-Baptiste Demoulin, Tsonwin Hai, Louise Deldicque, Marc Francaux
Activating transcription factor (ATF)3 regulates the expression of inflammation-related genes in several tissues under pathological contexts. In skeletal muscle, atf3 expression increases after exercise, but its target genes remain unknown. We aimed to identify those genes and to determine the influence of ATF3 on muscle adaptation to training. Skeletal muscles of ATF3-knockout (ATF3-KO) and control mice were analyzed at rest, after exercise, and after training. In resting muscles, there was no difference between genotypes in enzymatic activities or fiber type...
November 17, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27856430/glycolysis-and-oxidative-phosphorylation-are-essential-for-purinergic-receptor-mediated-angiogenic-responses-in-vasa-vasorum-endothelial-cells
#5
Martin Lapel, Philip Weston, Derek Strassheim, Vijaya Karoor, Nana Burns, Taras Lyubchenko, Petr Paucek, Kurt R Stenmark, Evgenia V Gerasimovskaya
Angiogenesis is an energy demanding process, however, the role of cellular energy pathways and their regulation by extracellular stimuli, especially extracellular nucleotides, remain largely unexplored. Using metabolic inhibitors of glycolysis (2-deoxyglucose, 2-DG) and oxidative phosphorylation (oligomycin, rotenone, and FCCP) we demonstrate that glycolysis and OXPHOS are both essential for angiogenic responses of vasa vasorum endothelial cell (VVEC). Treatment with P2R agonists, ATP and MeSADP, but not P1 receptor agonist, adenosine, increased glycolytic activity in VVEC (measured by extracellular acidification rate and lactate production)...
November 16, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27829129/resveratrol-inhibits-hexokinases-ii-mediated-glycolysis-in-non-small-cell-lung-cancer-via-targeting-akt-signaling-pathway
#6
Wei Li, Xiaoqian Ma, Na Li, Huasheng Liu, Qiong Dong, Juan Zhang, Cejun Yang, Yin Liu, Qi Liang, Shengwang Zhang, Chang Xu, Wei Song, Shiming Tan, Pengfei Rong, Wei Wang
Deregulation of glycolysis was often observed in human cancer cells. In the present study, we reported resveratrol, a small polyphenol, which has been intensively studied in various tumor models, has a profound anti-tumor effect on human non-small cell lung cancer (NSCLC) via regulation of glycolysis. Resveratrol impaired hexokinase II (HK2)-mediated glycolysis, and markedly inhibited anchorage-dependent and -independent growth of NSCLC cells. Exposure to resveratrol decreased EGFR and downstream kinases Akt and ERK1/2 activation...
November 6, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27824926/prognostic-significance-of-the-metabolic-marker-hexokinase-2-in-various-solid-tumors-a-meta-analysis
#7
Yulin Liu, Ke Wu, Liang Shi, Fan Xiang, Kaixiong Tao, Guobin Wang
OBJECTIVE: Recently, numerous studies have reported that hexokinase-2 (HK2) is aberrantly expressed in cancer, indicating that HK2 plays a pivotal role in the development and progression of cancer. However, its prognostic significance in solid tumor remains unclear. Accordingly, we performed a meta-analysis to assess the prognostic value of HK2 in solid tumor. METHODS: Eligible studies were identified using PubMed, Embase, and Web of Science databases. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) or progression-free survival (PFS)/disease-free survival (DFS)/relapse-free survival (RFS) were estimated with random effects or fixed effects models, respectively...
2016: PloS One
https://www.readbyqxmd.com/read/27809537/comprehensive-proteomics-analysis-reveals-metabolic-reprogramming-of-tumor-associated-macrophages-stimulated-by-the-tumor-microenvironment
#8
Di Liu, Cheng Chang, Ning Lu, Xing Wang, Qian Lu, Xiaojie Ren, Peng Ren, Dianyuan Zhao, Lijing Wang, Yunping Zhu, Fuchu He, Li Tang
Tumor-associated macrophages (TAMs) are major components of the tumor microenvironment. Although a role for TAMs in promoting tumor progression has been revealed, the differentiation mechanisms and intrinsic signals of TAMs regulated by the tumor microenvironment remain unclear. Here we constructed an in vitro TAMs cell model, TES-TAMs, which is from tumor-extract-stimulated bone-marrow-derived macrophages. We performed a comparative proteomics analysis of bone-marrow-derived macrophages and TES-TAMs, which indicated that TES-TAMs possessed characteristic molecular expression of TAMs...
November 3, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27784538/phenotyping-and-auto-antibody-production-by-liver-infiltrating-b-cells-in-primary-sclerosing-cholangitis-and-primary-biliary-cholangitis
#9
Brian K Chung, Bardia T Guevel, Gary M Reynolds, D B R K Gupta Udatha, Eva Kristine Klemsdal Henriksen, Zania Stamataki, Gideon M Hirschfield, Tom Hemming Karlsen, Evaggelia Liaskou
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are immune-mediated biliary diseases that demonstrate prominent and restricted genetic association with human leukocyte antigen (HLA) alleles. In PBC, anti-mitochondrial antibodies (AMA) are specific and used as diagnostic biomarkers. PSC-relevant auto-antibodies remain controversial despite a distinct HLA association that mirrors archetypical auto-antigen driven disorders. Herein, we compared antibody-secreting B cells (ASCs) in PSC and PBC liver explants to determine if liver-infiltrating ASCs represent an opportune and novel source of disease-relevant auto-antibodies...
October 24, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27784456/-the-role-of-hexokinase-2-in-the-metastasis-of-hepatocellular-carcinoma-cells
#10
X L Geng, W H Long, J Hai, Y Zhang, W Zheng, Z Y Zhang, L X Du
Objective: To investigate the regulatory role of HK2 in the metastasis of hepatocellular carcinoma (HCC). Methods: The protein expressions of HK2 in 73 HCC tumor tissues and paired adjacent non-tumor tissues were evaluated by using immunohistochemical analysis. The scratch wound healing assay and Transwell assay had been used to analyze the migration and invasion of HCC cells with HK2 knockdown. Expressions of epithelial-to-mesenchymal transition (EMT)markers, such as E-cadherin, ZO-1, N-cadherin and vimentin, in HCC cells with HK2 knockdown were determined by qRT-PCR and Western blot analysis...
October 23, 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/27777867/multivariate-analysis-and-molecular-interaction-of-curcumin-with-ppar%C3%AE-in-high-fructose-diet-induced-insulin-resistance-in-rats
#11
Vasanthi Jayakumar, Shiek S S J Ahmed, Kesavarao Kumar Ebenezar
To investigate the effect of curcumin on the multivariate and docking analysis on peroxisome proliferator activated receptor-γ, the rats were fed with high fructose diet (Group 2) to induce insulin resistance and curcumin was co-administered orally (Group 4) for a period of 8 weeks and measured the biochemical parameters in blood, kidney and liver tissues. The results showed a significant (p ≤ 0.05) increase in the level of creatinine, glucose, insulin, low density lipoprotein, total cholesterol, triglyceride, urea, uric acid, very low density lipoprotein and decreased albumin, high density lipoprotein and total protein level in the blood of Group 2 when compared with Group 1 control rats...
2016: SpringerPlus
https://www.readbyqxmd.com/read/27764724/innate-immune-cell-activation-and-epigenetic-remodeling-in-symptomatic-and-asymptomatic-atherosclerosis-in-humans-in%C3%A2-vivo
#12
Siroon Bekkering, Inge van den Munckhof, Tim Nielen, Evert Lamfers, Charles Dinarello, Joost Rutten, Jacqueline de Graaf, Leo A B Joosten, Mihai G Netea, Marc E R Gomes, Niels P Riksen
BACKGROUND AND AIMS: We have recently reported that monocytes can undergo functional and transcriptional reprogramming towards a long-term pro-inflammatory phenotype after brief in vitro exposure to atherogenic stimuli such as oxidized LDL. This process is termed 'trained immunity', and is mediated by epigenetic remodeling and a metabolic switch towards increased aerobic glycolysis. We hypothesize that trained immunity contributes to atherogenesis. Therefore, we investigated the inflammatory phenotype and epigenetic remodeling of monocytes from patients with and without established atherosclerosis...
October 12, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/27752131/traf3-deficiency-promotes-metabolic-reprogramming-in-b-cells
#13
Nurbek Mambetsariev, Wai W Lin, Alicia M Wallis, Laura L Stunz, Gail A Bishop
The adaptor protein TNF receptor-associated factor 3 (TRAF3) is a critical regulator of B lymphocyte survival. B cell-specific TRAF3 deficiency results in enhanced viability and is associated with development of lymphoma and multiple myeloma. We show that TRAF3 deficiency led to induction of two proteins important for glucose metabolism, Glut1 and Hexokinase 2 (HXK2). This was associated with increased glucose uptake. In the absence of TRAF3, anaerobic glycolysis and oxidative phosphorylation were increased in B cells without changes in mitochondrial mass or reactive oxygen species...
October 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27748854/hypoxia-induces-glucose-uptake-and-metabolism-of-adipose%C3%A2-derived-stem-cells
#14
Hyoung Sook Park, Ji Hye Kim, Bo Kyung Sun, Sun U Song, Wonhee Suh, Jong-Hyuk Sung
It has previously been demonstrated that hypoxia has diverse stimulatory effects on adipose‑derived stem cells (ASCs), however, metabolic responses under hypoxia remain to be elucidated. Thus, the present study aimed to investigate the glucose uptake and metabolism of ASCs under hypoxic conditions, and to identify the underlying molecular mechanisms. ASCs were cultured in 1% oxygen, and experiments were conducted in vitro. As determined by proteomic analysis and western blotting, GAPDH and enolase 1 (ENO1) expression were upregulated under hypoxia...
October 5, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27720417/maintaining-a-clinical-weight-loss-after-intensive-lifestyle-intervention-is-the-key-to-cardiometabolic-health
#15
Sune Dandanell, Camilla Skovborg, Charlotte Boslev Præst, Kasper Bøgh Kristensen, Malene Glerup Nielsen, Sofie Lionett, Sofie Drevsholt Jørgensen, Andreas Vigelsø, Flemming Dela, Jørn Wulff Helge
OBJECTIVE: Intensive lifestyle interventions (ILI) are criticised for ineffective obesity treatment because weight loss over time is modest and thus of limited clinical relevance. However, a subgroup (5-30%) maintains a clinical weight loss >10%, but it is not clear if cardiometabolic health follows this pattern. The aim was to study the effect of different magnitudes of weight loss maintenance after ILI on cardiometabolic health. METHODS: Eighty out of 2420 former participants (age: 36±1, BMI: 38±1, (means ±SE)) in an 11-12-week ILI were recruited into 3 groups; clinical weight loss maintenance (>10% weight loss), moderate maintenance (1-10%), and weight regain based on weight loss at follow-up (5...
October 5, 2016: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/27662473/antidiabetic-and-antihyperlipidemic-activity-of-p-coumaric-acid-in-diabetic-rats-role-of-pancreatic-glut-2-in-vivo-approach
#16
Venkatesan Amalan, Natesan Vijayakumar, Dhananjayan Indumathi, Arumugam Ramakrishnan
P-coumaric acid (p-CA, 3-[4-hydroxyphenyl]-2-propenoic acid), the major component widely found in nutritious plant foods, has various antioxidant, antiinflammatory and anticancer property. To evaluate the antidiabetic and antihyperlipidemic mechanisms, via the effects on carbohydrate, lipids and lipoproteins responses in adult male albino Wistar rats were examined by treated with p-CA. Rats were injected with streptozotocin (STZ, 40mg/kg b.w.) by intraperitonially (i.p.) 30days for the induction of experimental diabetes mellitus...
September 20, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27588472/targeting-hexokinase-2-enhances-response-to-radio-chemotherapy-in-glioblastoma
#17
Alenoush Vartanian, Sameer Agnihotri, Mark R Wilson, Kelly E Burrell, Peter D Tonge, Amir Alamsahebpour, Shahrzad Jalali, Michael S Taconne, Brian Golbourn, Kenneth D Aldape, Gelareh Zadeh
First-line cancer therapies such as alkylating agents and radiation have limited survival benefits for Glioblastoma (GBM) patients. Current research strongly supports the notion that inhibition of aberrant tumor metabolism holds promise as a therapeutic strategy when used in combination with radiation and chemotherapy. Hexokinase 2 (HK2) has been shown to be a key driver of altered metabolism in GBM, and presents an attractive therapeutic target. To date, no study has fully assessed the therapeutic value of targeting HK2 as a mechanism to sensitize cells to standard therapy, namely in the form of radiation and temozolomide (TMZ)...
August 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27574783/-18-f-fdg-pet-ct-for-monitoring-the-response-of-breast-cancer-to-mir-143-based-therapeutics-by-targeting-tumor-glycolysis
#18
Ying Miao, Ling-Fei Zhang, Rui Guo, Sheng Liang, Min Zhang, Shuo Shi, Cheng-Fang Shang-Guan, Mo-Fang Liu, Biao Li
Increased glucose utilization is a hallmark of cancer, and tumor metabolism is emerging as anticancer target for therapeutic intervention. Triple-negative breast cancers TNBC are highly glycolytic and show poor clinical outcomes. We previously identified hexokinase 2, the major glycolytic enzyme, as a target gene of miR-143 in TNBC. Here, we developed a therapeutic formulation using cholesterol-modified miR-143 agomir encapsulated in a neutral lipid-based delivery agent that blocked tumor growth and glucose metabolism in TNBC tumor-bearing mice when administered systemically...
2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27560976/glucose-sensor-mdhxk1-phosphorylates-and-stabilizes-mdbhlh3-to-promote-anthocyanin-biosynthesis-in-apple
#19
Da-Gang Hu, Cui-Hui Sun, Quan-Yan Zhang, Jian-Ping An, Chun-Xiang You, Yu-Jin Hao
Glucose induces anthocyanin accumulation in many plant species; however, the molecular mechanism involved in this process remains largely unknown. Here, we found that apple hexokinase MdHXK1, a glucose sensor, was involved in sensing exogenous glucose and regulating anthocyanin biosynthesis. In vitro and in vivo assays suggested that MdHXK1 interacted directly with and phosphorylated an anthocyanin-associated bHLH transcription factor (TF) MdbHLH3 at its Ser361 site in response to glucose. Furthermore, both the hexokinase_2 domain and signal peptide are crucial for the MdHXK1-mediated phosphorylation of MdbHLH3...
August 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27555469/levels-of-betatrophin-decrease-during-pregnancy-despite-increased-insulin-resistance-beta-cell-function-and-triglyceride-levels
#20
A Zielińska, R Maciulewski, K Siewko, A Popławska-Kita, D Lipińska, G Kozłowska, M Górska, M Szelachowska
AIM: Evidence in support of an association between betatrophin and insulin resistance (IR) is mounting, with studies demonstrating that betatrophin is elevated in patients with type 2 diabetes, obesity and gestational diabetes. The aim of this study was to evaluate the role of betatrophin in IR and physiological proliferation of beta cells during pregnancy in healthy women. METHODS: Eighty healthy pregnant women were examined at each trimester [T1 (first), T2 (second), T3 (third)], with a subgroup (n=45) that was also examined at 3 months postpartum (3MPP)...
August 20, 2016: Diabetes & Metabolism
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