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Hexokinase 2

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
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
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
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
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
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
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
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
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
Dawei Zhang, Yew Mun Yip, Liben Li
Hexokinase 2 (HK2) binds to Voltage-Dependent Anion Channel 1 (VDAC1) on mitochondrial outer membrane (MOM) to facilitate a preferential access of ATP to HK2 for glycolysis, in order to maintain a constant energy source for cell proliferation in cancer especially. While previous studies have discovered that the VDAC1 N-terminal helix is responsible for regulating molecules from within mitochondria to cytoplasm, the molecular mechanism of how HK2 is able to regulate the ATP access remains elusive. We hereby propose a model for the HK2-VDAC1 association...
September 2016: Mitochondrion
Han Sung Kim, Yeong-Min Yoo
Autophagy appears to be involved in maintaining normal intracellular insulin content by accelerating the insulin degradation rate in β-cells (Marsh et al., 2007) [1]. 2-deoxy-d-glucose (2-DG) is metabolized by hexokinase, and acts as an inhibitor of glycolysis. 2-DG triggers glucose deprivation without altering other nutrients or metabolic pathways (Aghaee et al., 2012) [2], and appears to be an ideal tool for studying autophagy. Rapamycin induced upregulation of autophagy in both cultured isolated islets and pancreatic β-cells (Tanemura et al...
September 2016: Data in Brief
M J Meneses, R L Bernardino, R Sá, J Silva, A Barros, M Sousa, B M Silva, P F Oliveira, M G Alves
Pioglitazone is a synthetic agonist for the nuclear receptor peroxisome proliferator-activated receptor γ used to treat type 2 diabetes mellitus. Recently we reported that antidiabetic drugs regulate the nutritional support of spermatogenesis by Sertoli cells. Herein, we investigate the effects of pioglitazone on human Sertoli cells metabolism. Human Sertoli cells were cultured in the presence of pioglitazone (1, 10, 100μM). Protein levels of phosphofructokinase 1, lactate dehydrogenase, hexokinase, glucose transporters (GLUT1, GLUT2, GLUT3), monocarboxylate transporter 4 and oxidative phosphorylation complexes were determined by Western blot...
October 2016: International Journal of Biochemistry & Cell Biology
Peter J Siska, Gerritje J W van der Windt, Rigel J Kishton, Sivan Cohen, William Eisner, Nancie J MacIver, Arnon P Kater, J Brice Weinberg, Jeffrey C Rathmell
Leukemia can promote T cell dysfunction and exhaustion that contributes to increased susceptibility to infection and mortality. The treatment-independent mechanisms that mediate leukemia-associated T cell impairments are poorly understood, but metabolism tightly regulates T cell function and may contribute. In this study, we show that B cell leukemia causes T cells to become activated and hyporesponsive with increased PD-1 and TIM3 expression similar to exhausted T cells and that T cells from leukemic hosts become metabolically impaired...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Franziska Visser, Boje Müller, Judith Rose, Dirk Prüfer, Gundula A Noll
The immobilisation of enzymes plays an important role in many applications, including biosensors that require enzyme activity, stability and recyclability in order to function efficiently. Here we show that forisomes (plant-derived mechanoproteins) can be functionalised with enzymes by translational fusion, leading to the assembly of structures designated as forizymes. When forizymes are expressed in the yeast Saccharomyces cerevisiae, the enzymes are immobilised by the self-assembly of forisome subunits to form well-structured protein bodies...
2016: Scientific Reports
Fernando Moreno, Montserrat Vega, Pilar Herrero
No abstract text is available yet for this article.
August 5, 2016: Journal of Biological Chemistry
Akshay Vishwanatha, Charalampos Rallis, Shubha Bevkal Subramanyaswamy, Cletus Joseph Michael D'Souza, Jürg Bähler, Martin Ernst Schweingruber
2-Deoxyglucose (2-DG) is a toxic glucose analog. To identify genes involved in 2-DG toxicity in Schizosaccharomyces pombe, we screened a wild-type overexpression library for genes which render cells 2-DG resistant. A gene we termed odr1, encoding an uncharacterized hydrolase, led to strong resistance and altered invertase expression when overexpressed. We speculate that Odr1 neutralizes the toxic form of 2-DG, similar to the Saccharomyces cerevisiae Dog1 and Dog2 phosphatases which dephosphorylate 2-DG-6-phosphate synthesized by hexokinase...
September 2016: FEMS Yeast Research
Brian E Fratto, Nataliia Guz, Tyler T Fallon, Evgeny Katz
An enzyme-based 1:2 demultiplexer has been designed in a flow system composed of three cells where each one is modified with a different enzyme: hexokinase, glucose dehydrogenase and glucose-6-phosphate dehydrogenase. The Input signal activating the biocatalytic cascade was represented by glucose, while the Address signal represented by ATP was responsible for directing the Input signal to one of the output channels, depending on the logic value of the Address. The biomolecular 1:2 demultiplexer was extended to include two electrochemical actuators releasing entrapped DNA molecules in the active output channel...
August 2, 2016: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
Yong-Hua Liu, Christina E Offler, Yong-Ling Ruan
Reduced cell wall invertase (CWIN) activity has been shown to be associated with poor seed and fruit set under abiotic stress. Here, we examined whether genetically increasing native CWIN activity would sustain fruit set under long-term moderate heat stress (LMHS), an important factor limiting crop production, by using transgenic tomato (Solanum lycopersicum) with its CWIN inhibitor gene silenced and focusing on ovaries and fruits at 2 d before and after pollination, respectively. We found that the increase of CWIN activity suppressed LMHS-induced programmed cell death in fruits...
September 2016: Plant Physiology
Elja Eskes, Tobias Wilms, Joris Winderickx
No abstract text is available yet for this article.
July 26, 2016: Cell Cycle
Anton E Ludvik, Carolina M Pusec, Medha Priyadarshini, Anthony R Angueira, Cong Guo, Amy Lo, Korri S Hershenhouse, Guang-Yu Yang, Xianzhong Ding, Timothy E Reddy, William L Lowe, Brian T Layden
In a recent genome-wide association study, hexokinase domain-containing protein 1, or HKDC1, was found to be associated with gestational glucose levels during 2-hour glucose tolerance tests at 28 weeks of pregnancy. Because our understanding of the mediators of gestational glucose homeostasis is incomplete, we have generated the first transgenic mouse model to begin to understand the role of HKDC1 in whole-body glucose homeostasis. Interestingly, deletion of both HKDC1 alleles results in in utero embryonic lethality...
September 2016: Endocrinology
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