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Hexokinase 2

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https://www.readbyqxmd.com/read/28345119/metabolism-of-mannose-in-cultured-primary-rat-neurons
#1
Wiebke Rastedt, Eva-Maria Blumrich, Ralf Dringen
Glucose is the main peripheral substrate for energy production in the brain. However, as other hexoses are present in blood and cerebrospinal fluid, we have investigated whether neurons have the potential to metabolize, in addition to glucose, also the hexoses mannose, fructose or galactose. Incubation of primary cerebellar granule neurons in the absence of glucose caused severe cell toxicity within 24 h, which could not be prevented by application of galactose or fructose, while the cells remained viable during incubation in the presence of either mannose or glucose...
March 27, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28327594/aspirin-induces-cell-death-by-directly-modulating-mitochondrial-voltage-dependent-anion-channel-vdac
#2
Debanjan Tewari, Dhriti Majumdar, Sirisha Vallabhaneni, Amal Kanti Bera
Aspirin induces apoptotic cell death in various cancer cell lines. Here we showed that silencing of VDAC1 protected HeLa cells from aspirin-induced cell death. Compared to the wild type cells, VDAC1 knocked down cells showed lesser change of mitochondrial membrane potential (Δψm), upon aspirin treatment. Aspirin augmented ATP and ionomycin-induced mitochondrial Ca(2+) uptake which was abolished in VDAC1 knocked down cells. Aspirin dissociated bound hexokinase II (HK-II) from mitochondria. Further, aspirin promoted the closure of recombinant human VDAC1, reconstituted in planar lipid bilayer...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322782/cl-316-243-mediated-reductions-in-blood-glucose-are-enhanced-in-rip140-mice-independent-of-alterations-in-lipolysis
#3
Willem T Peppler, Paula M Miotto, Graham P Holloway, David C Wright
The β-3 adrenergic agonist CL 316, 243 acutely lowers blood glucose through a mechanism thought to involve fatty-acid induced insulin release. The purpose of this study was to determine if ablation of the nuclear receptor, receptor-inactivating protein 140 (RIP140), altered this response. Here, we used a single injection of CL 316, 243 (1 mg/kg) and found that whole body RIP140(-/-) mice had a greater decline in blood glucose over 2 h. This occurred alongside increased hexokinase II (HKII) protein content in adipose tissue and skeletal muscle, but independent of changes in circulating insulin or indices of lipolysis...
March 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28320429/chrysin-inhibited-tumor-glycolysis-and-induced-apoptosis-in-hepatocellular-carcinoma-by-targeting-hexokinase-2
#4
Dong Xu, Junzhe Jin, Hao Yu, Zheming Zhao, Dongyan Ma, Chundong Zhang, Honglei Jiang
BACKGROUND: Hexokinase-2(HK-2) plays dual roles in glucose metabolism and mediation of cell apoptosis, making it an attractive target for cancer therapy. Chrysin is a natural flavone found in plant extracts which are widely used as herb medicine in China. In the present study, we investigated the antitumor activity of chrysin against hepatocellular carcinoma (HCC) and the role of HK-2 played for chrysin to exert its function. METHODS: The expression of HK-2 in HCC cell line and tumor tissue was examined by western blotting and immunohistochemistry staining...
March 20, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28303258/alterations-in-cytosolic-and-mitochondrial-u-13-c-glucose-metabolism-in-a-chronic-epilepsy-mouse-model
#5
Tanya S McDonald, Catalina Carrasco-Pozo, Mark P Hodson, Karin Borges
Temporal lobe epilepsy is a common form of adult epilepsy and shows high resistance to treatment. Increasing evidence has suggested that metabolic dysfunction contributes to the development of seizures, with previous studies indicating impairments in brain glucose metabolism. Here we aim to elucidate which pathways involved in glucose metabolism are impaired, by tracing the hippocampal metabolism of injected [U-(13)C]glucose (i.p.) during the chronic stage of the pilocarpine-status epilepticus mouse model of epilepsy...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28290047/adaptation-to-chronic-continuous-hypoxia-potentiates-akt-hk2-anti-apoptotic-pathway-during-brief-myocardial-ischemia-reperfusion-insult
#6
David Kolar, Milada Gresikova, Petra Waskova-Arnostova, Barbara Elsnicova, Jana Kohutova, Daniela Hornikova, Pavel Vebr, Jan Neckar, Tereza Blahova, Dita Kasparova, Jiri Novotny, Frantisek Kolar, Olga Novakova, Jitka M Zurmanova
Adaptation to chronic hypoxia represents a potential cardioprotective intervention reducing the extent of acute ischemia/reperfusion (I/R) injury, which is a major cause of death worldwide. The main objective of this study was to investigate the anti-apoptotic Akt/hexokinase 2 (HK2) pathway in hypoxic hearts subjected to I/R insult. Hearts isolated from male Wistar rats exposed either to continuous normobaric hypoxia (CNH; 10% O2) or to room air for 3 weeks were perfused according to Langendorff and subjected to 10 min of no-flow ischemia and 10 min of reperfusion...
March 13, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28288978/mff-dependent-mitochondrial-fission-contributes-to-the-pathogenesis-of-cardiac-microvasculature-ischemia-reperfusion-injury-via-induction-of-mros-mediated-cardiolipin-oxidation-and-hk2-vdac1-disassociation-involved-mptp-opening
#7
Hao Zhou, Shunying Hu, Qinhua Jin, Chen Shi, Ying Zhang, Pingjun Zhu, Qiang Ma, Feng Tian, Yundai Chen
BACKGROUND: The cardiac microvascular system ischemia/reperfusion injury following percutaneous coronary intervention is a clinical thorny problem. This study explores the mechanisms by which ischemia/reperfusion injury induces cardiac microcirculation collapse. METHODS AND RESULTS: In wild-type mice, mitochondrial fission factor (Mff) expression increased in response to acute microvascular ischemia/reperfusion injury. Compared with wild-type mice, homozygous Mff-deficient (Mff(gt)) mice exhibited a smaller infarcted area, restored cardiac function, improved blood flow, and reduced microcirculation perfusion defects...
March 13, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28284804/novel-highly-potent-systemic-glucokinase-activators-for-the-treatment-of-type-2-diabetes-mellitus
#8
Jiayi Xu, Songnian Lin, Robert W Myers, George Addona, Joel P Berger, Brian Campbell, Hsuan-Shen Chen, Zhesheng Chen, George J Eiermann, Nadine H Elowe, Brian T Farrer, Wen Feng, Qinghong Fu, Roman Kats-Kagan, Michael Kavana, Sunita Malkani, Daniel R McMasters, Kaushik Mitra, Michele J Pachanski, Xinchun Tong, Maria E Trujillo, Libo Xu, Bei Zhang, Fengqi Zhang, Rui Zhang, Emma R Parmee
Glucokinase (GK, hexokinase IV) is a unique hexokinase that plays a central role in mammalian glucose homeostasis. Glucose phosphorylation by GK in the pancreatic β-cell is the rate-limiting step that controls glucose-stimulated insulin secretion. Similarly, GK-mediated glucose phosphorylation in hepatocytes plays a major role in increasing hepatic glucose uptake and metabolism and possibly lowering hepatic glucose output. Small molecule GK activators (GKAs) have been identified that increase enzyme activity by binding to an allosteric site...
October 31, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28283400/vdac-in-cancer
#9
REVIEW
N M Mazure
The voltage-dependent anion channel (VDAC) is a pore located at the outer membrane of the mitochondrion. It allows the entry and exit of numerous ions and metabolites between the cytosol and the mitochondrion. Flux through the pore occurs in an active way: first, it depends on the open or closed state and second, on the negative or positive charges of the different ion species passing through the pore. The flux of essential metabolites, such as ATP, determines the functioning of the mitochondria to a noxious stimulus...
March 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28264838/loss-of-brca1-in-the-cells-of-origin-of-ovarian-cancer-induces-glycolysis-a-window-of-opportunity-for-ovarian-cancer-chemoprevention
#10
Tatsuyuki Chiyoda, Peter C Hart, Mark A Eckert, Stephanie M McGregor, Ricardo R Lastra, Ryuji Hamamoto, Yusuke Nakamura, S Diane Yamada, Olufunmilayo I Olopade, Ernst Lengyel, Iris L Romero
Mutations in the breast cancer susceptibility gene 1 (BRCA1) are associated with an increased risk of developing epithelial ovarian cancer. However, beyond the role of BRCA1 in DNA repair, little is known about other mechanisms by which BRCA1 impairment promotes carcinogenesis. Given that altered metabolism is now recognized as important in the initiation and progression of cancer, we asked whether loss of BRCA1 changes metabolism in the cells of origin of ovarian cancer. The findings show that silencing BRCA1 in ovarian surface epithelial and fallopian tube cells increased glycolysis...
March 6, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28247243/grape-hexokinases-are-involved-in-the-expression-regulation-of-sucrose-synthase-and-cell-wall-invertase-encoding-genes-by-glucose-and-aba
#11
Xiu-Qin Wang, Li-Li Zheng, Hao Lin, Fei Yu, Li-Hui Sun, Li-Mei Li
Hexokinase (HXK, EC 2.7.1.1) is a multifunctional protein that both is involved in catalyzing the first step of glycolysis and plays an important role in sugar signaling. However, the supporting genetic evidence on hexokinases (CsHXKs) from grape (Vitis vinifera L. cv. Cabernet Sauvignon) berries has been lacking. Here, to investigate the role of CsHXK isoforms as glucose (Glc) and abscisic acid (ABA) sensors, we cloned two hexokinase isozymes, CsHXK1 and CsHXK2 with highly conserved genomic structure of nine exons and eight introns...
February 28, 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/28243449/performance-of-the-freestyle-libre-flash-glucose-monitoring-system-in-patients-with-type-1-and-2-diabetes-mellitus
#12
M J Fokkert, P R van Dijk, M A Edens, S Abbes, D de Jong, R J Slingerland, H J G Bilo
OBJECTIVE: To evaluate the performance of the FreeStyle Libre Flash continuous glucose monitoring (FSL-CGM) system against established central laboratory methods. RESEARCH DESIGN AND METHODS: 20 subjects (8 type 1 diabetes mellitus, 12 type 2 diabetes mellitus) were analyzed. FSL-CGM sensor measurements (inserted in arm and abdomen) were compared with capillary blood glucose results analyzed with StatStrip as semigold standard. The glucose response after a standardized oral glucose load was measured by FSL-CGM and capillary samples analyzed by perchloric acid hexokinase (PCA-HK) method, StatStrip and FSL test strip (FSLC), and a commonly used CGM system (iPro2)...
2017: BMJ Open Diabetes Research & Care
https://www.readbyqxmd.com/read/28237630/-18-f-fluoro-2-deoxyglucose-pet-informs-neutrophil-accumulation-and-activation-in-lipopolysaccharide-induced-acute-lung-injury
#13
Rosana S Rodrigues, Fernando A Bozza, Christopher J Hanrahan, Li-Ming Wang, Qi Wu, John M Hoffman, Guy A Zimmerman, Kathryn A Morton
INTRODUCTION: Molecular imaging of the earliest events related to the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) could facilitate therapeutic development and patient management. We previously reported that (18)F-fluoro-2-deoxyglucose ((18)F-FDG) PET identifies ALI/ARDS prior to radiographic abnormalities. The purpose of this study was to establish the time courses of (18)F-FDG uptake, edema and neutrophil recruitment in an endotoxin-induced acute lung injury model and to examine molecular events required for (14)C-2DG uptake in activated neutrophils...
January 17, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28224194/mycoepoxydiene-suppresses-hela-cell-growth-by-inhibiting-glycolysis-and-the-pentose-phosphate-pathway
#14
Kehua Jin, Li Li, Xihuan Sun, Qingyan Xu, Siyang Song, Yuemao Shen, Xianming Deng
Upregulation of glycolysis and the pentose phosphate pathway (PPP) is a major characteristic of the metabolic reprogramming of cancer and provides cancer cells with energy and vital metabolites to support their rapid proliferation. Targeting glycolysis and the PPP has emerged as a promising antitumor therapeutic strategy. Marine natural products are attractive sources for anticancer therapeutics, as evidenced by the antitumor drug Yondelis. Mycoepoxydiene (MED) is a natural product isolated from a marine fungus that has shown promising inhibitory efficacy against HeLa cells in vitro...
February 21, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28193094/protective-effects-of-ficus-carica-leaves-on-glucose-and-lipids-levels-carbohydrate-metabolism-enzymes-and-%C3%AE-cells-in-type-2-diabetic-rats
#15
COMPARATIVE STUDY
Santiagu Stephen Irudayaraj, Sunil Christudas, Stalin Antony, Veeramuthu Duraipandiyan, Al-Dhabi Naif Abdullah, Savarimuthu Ignacimuthu
CONTEXT: The decoctions of Ficus carica Linn. (Moraceae) leaves are used in the folklore treatment of diabetes. OBJECTIVE: To evaluate the effect of F. carica on glucose and lipids levels, carbohydrate metabolism enzymes and β-cells protective effects in type 2 diabetes. MATERIAL AND METHODS: Diabetes was induced in 15 days high-fat diet (HFD)-fed Wistar rats by intraperitoneal injection of streptozotocin (STZ) (40 mg/kg). The ethyl acetate extract (250 and 500 mg/kg) of F...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28186160/3-bromopyruvate-ameliorate-autoimmune-arthritis-by-modulating-th17-treg-cell-differentiation-and-suppressing-dendritic-cell-activation
#16
Takaichi Okano, Jun Saegusa, Keisuke Nishimura, Soshi Takahashi, Sho Sendo, Yo Ueda, Akio Morinobu
Recent studies have shown that cellular metabolism plays an important role in regulating immune cell functions. In immune cell differentiation, both interleukin-17-producing T (Th17) cells and dendritic cells (DCs) exhibit increased glycolysis through the upregulation of glycolytic enzymes, such as hexokinase-2 (HK2). Blocking glycolysis with 2-deoxyglucose was recently shown to inhibit Th17 cell differentiation while promoting regulatory T (Treg) cell generation. However, 2-DG inhibits all isoforms of HK. Thus, it is unclear which isoform has a critical role in Th17 cell differentiation and in rheumatoid arthritis (RA) pathogenesis...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28184935/involvement-of-ezh2-in-aerobic-glycolysis-of-prostate-cancer-through-mir-181b-hk2-axis
#17
Tao Tao, Ming Chen, Ranran Jiang, Han Guan, Yeqing Huang, Huan Su, Qiang Hu, Xu Han, Jun Xiao
Recent studies suggest that several types of tumors preferentially metabolize glucose through aerobic glycolysis, a phenomenon known as the Warburg effect. However, it remains largely unexplored whether metabolic reprogramming is involved in prostate cancer (PCa) progression. In this study, we found that histone methyltransferase enhancer of zeste homolog 2 (EZH2) dysregulated in PCa development regulated cellular growth and aerobic glycolysis through miR-181b/hexokinase 2 (HK2) axis. Aberrant expression profiles of coding RNA and microRNA were examined by two large, independent clinical prostate cancer data sets...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28179998/phlpp-regulates-hexokinase-2-dependent-glucose-metabolism-in-colon-cancer-cells
#18
Xiaopeng Xiong, Yang-An Wen, Mihail I Mitov, Mary C Oaks, Shigeki Miyamoto, Tianyan Gao
Increased glucose metabolism is considered as one of the most important metabolic alterations adapted by cancer cells in order to generate energy as well as high levels of glycolytic intermediates to support rapid proliferation. PH domain leucine-rich repeat protein phosphatase (PHLPP) belongs to a novel family of Ser/Thr protein phosphatases that function as tumor suppressors in various types of human cancer. Here we determined the role of PHLPP in regulating glucose metabolism in colon cancer cells. Knockdown of PHLPP increased the rate of glucose consumption and lactate production, whereas overexpression of PHLPP had the opposite effect...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28174335/microrna-143-suppresses-oral-squamous-cell-carcinoma-oscc-cell-growth-invasion-and-glucose-metabolism-through-targeting-hexokinase2
#19
Xianghui Sun, Lei Zhang
MicroRNAs are non-coding RNAs that have functions to regulate gene expression and play essential roles in a variety of biological processes of cancers. In this study, we report miR-143 acts as a tumor suppressor in human oral squamous cell carcinoma (OSCC). The expressions of miR-143 are downregulated in both oral squamous cell carcinoma cell lines and patient samples compared with normal adjacent tissues. We found overexpression of miR-143 in oral cancer cell lines suppresses cell migration, cellular glucose metabolism and proliferation...
February 7, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28131825/targeting-hexokinase-ii-as-a-possible-therapy-for-cholangiocarcinoma
#20
Ubonrat Thamrongwaranggoon, Wunchana Seubwai, Chatchai Phoomak, Sakkarn Sangkhamanon, Ubon Cha'on, Thidarat Boonmars, Sopit Wongkham
Overexpression of hexokinase 2 (HKII) has been demonstrated in various cancers. A number of in vitro and in vivo studies in several cancers show the significance of HKII in many cellular processes including proliferation, metastasis and apoptosis. However, the role of HKII in Opisthorchis viverrini (Ov) associated cholangiocarcinoma (CCA) is still unknown. In the present study, the expression and roles of HKII were determined in Ov associated CCA. The expression of HKII was investigated in 82 patients with histologically proven CCAs by immunohistochemistry...
January 25, 2017: Biochemical and Biophysical Research Communications
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