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Hexokinase

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https://www.readbyqxmd.com/read/28077391/acclimation-to-hypoxia-increases-carbohydrate-use-during-exercise-in-high-altitude-deer-mice
#1
Daphne S Lau, Alex D Connaty, Sajeni Mahalingam, Nastashya Wall, Zachary A Cheviron, Jay F Storz, Graham R Scott, Grant B McClelland
The low oxygen experienced at high altitude is a significant challenge to effective aerobic locomotion, as it requires sustained tissue oxygen delivery in addition to the appropriate allocation of metabolic substrates. Here we test whether high- and low-altitude deer mice (Peromyscus maniculatus) have evolved different acclimation responses to hypoxia with respect to muscle metabolism and fuel use during submaximal exercise. Using F1-generation high- and low-altitude deer mice that were born and raised in common conditions, we assessed 1) fuel use during exercise, 2) metabolic enzyme activities, and 3) gene expression for key transporters and enzymes in the gastrocnemius...
January 11, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28068632/hydroxysafflor-yellow-a-cardioprotection-in-ischemia-reperfusion-i-r-injury-mainly-via-akt-hexokinase-ii-independent-of-erk-gsk-3%C3%AE-pathway
#2
Jia Min, Cui Wei
Hydroxysafflor yellow A (HSYA) is the main active component of Carthamus tinctorius L which has been used for hundreds of years in Chinese folk medicine in the treatment cardiovascular disease. This study was designed to investigate whether HSYA exerts cardioprotection in ischemia-reperfusion (I/R) injury heart and the mechanisms involved. The protective effect and mechanisms in myocardial ischemia reperfusion injury of HSYA was evaluated by hypoxia-recover (H/R) injury cell model which induced by hypoxia and recovered with oxygen in H9c2 cells...
January 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28063798/evaluation-of-biological-properties-of-3-3-4-4-benzophenonetetracarboxylic-dianhydride-derivatives-and-their-ability-to-inhibit-hexokinase-activity
#3
Krzysztof Kochel, Mateusz D Tomczyk, Rui F Simões, Tomasz Frączek, Adrian Soboń, Paulo J Oliveira, Krzysztof Z Walczak, Aneta Koceva-Chyła
This investigation has explored the properties of 3,3',4,4'-benzophenonetetracarboxylic dianhydride (BDTA) derivatives with regard to their being prospective inhibitors of hexokinase II (HKII). A pluripotent embryonic carcinoma cell line P19 (ECC), was used as the biological target for newly generated potential inhibitors of HKII. The results obtained from Virtual High-Throughput Screening (VHTS), molecular modeling and biological activity studies showed BDTA to be a promising leading structure with a good binding score and simplest functionalization...
December 25, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28063005/albendazole-inhibits-hif-1%C3%AE-dependent-glycolysis-and-vegf-expression-in-non-small-cell-lung-cancer-cells
#4
Fang Zhou, Jin Du, Jianjun Wang
Albendazole (ABZ) has an anti-tumor ability and inhibits HIF-1α activity. HIF-1α is associated with glycolysis and vascular endothelial cell growth factor (VEGF) expression, which plays an important role in cancer progression. These clues indicate that ABZ exerts an anti-cancer effect by regulating glycolysis and VEGF expression. The aim of this study is to clarify the effects of ABZ on non-small cell lung cancer (NSCLC) cells and explore the underlying molecular mechanisms. The expression levels of HIF-1α and VEGF were detected using western blot analysis, and the effect of ABZ on glycolysis was evaluated by measuring the relative activities of hexokinase (HK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) and detecting the production of lactate in A549 and H1299 cells...
January 7, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28060833/wnt-signaling-prevents-the-a%C3%AE-oligomer-induced-mitochondrial-permeability-transition-pore-opening-preserving-mitochondrial-structure-in-hippocampal-neurons
#5
Macarena S Arrázola, Eva Ramos-Fernández, Pedro Cisternas, Daniela Ordenes, Nibaldo C Inestrosa
Alzheimer's disease (AD) is a neurodegenerative disorder mainly known for synaptic impairment and neuronal cell loss, affecting memory processes. Beside these damages, mitochondria have been implicated in the pathogenesis of AD through the induction of the mitochondrial permeability transition pore (mPTP). The mPTP is a non-selective pore that is formed under apoptotic conditions, disturbing mitochondrial structure and thus, neuronal viability. In AD, Aβ oligomers (Aβos) favor the opening of the pore, activating mitochondria-dependent neuronal cell death cascades...
2017: PloS One
https://www.readbyqxmd.com/read/28056994/hexokinase-2-drives-glycogen-accumulation-in-equine-endometrium-at-day-12-of-diestrus-and-pregnancy
#6
Sarah A Bramer, Alysson Macedo, Claudia Klein
BACKGROUND: Secretion of histotroph during the prolonged pre-implantation phase in mares is crucial to pregnancy maintenance, manifested as increased embryonic loss in mares with age-related endometrial degeneration. Glycogen content of uterine histotroph is higher during the progesterone-dominated phase of the estrous cycle in mares, but regulatory mechanisms are not well understood. METHODS: mRNA expression of glycogen-metabolizing enzymes (HK1, HK2, GSK3B, GYS1, PEPCK, PKM, PYGM) in endometrial samples were compared among mares in anestrus, estrus, and at Day 12 of diestrus and pregnancy...
January 5, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28054552/c-src-phosphorylation-and-activation-of-hexokinase-promotes-tumorigenesis-and-metastasis
#7
Jia Zhang, Suili Wang, Bin Jiang, Lihong Huang, Zhiliang Ji, Xiaotong Li, Huamin Zhou, Aidong Han, Ai Chen, Yanan Wu, Huanhuan Ma, Wentao Zhao, Qingwen Zhao, Changchuan Xie, Xiaoyan Sun, Yanming Zhou, Huiying Huang, Muhammad Suleman, Furong Lin, Lin Zhou, Fang Tian, Meijun Jin, Yana Cai, Nan Zhang, Qinxi Li
It is well known that c-Src has important roles in tumorigenesis. However, it remains unclear whether c-Src contributes to metabolic reprogramming. Here we find that c-Src can interact with and phosphorylate hexokinases HK1 and HK2, the rate-limiting enzymes in glycolysis. Tyrosine phosphorylation dramatically increases their catalytic activity and thus enhances glycolysis. Mechanistically, c-Src phosphorylation of HK1 at Tyr732 robustly decreases its Km and increases its Vmax by disrupting its dimer formation...
January 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28049096/anti-diabetic-effect-of-three-new-norditerpenoid-alkaloids-in-vitro-and-potential-mechanism-via-pi3k-akt-signaling-pathway
#8
Dan Tang, Qi-Bin Chen, Xue-Lei Xin, Haji-Akber Aisa
Diabetes is a metabolic disease with the characteristic of high blood glucose (hyperglycemia). In our previous study, we found that nigelladines A-C (compounds A-C), three norditerpenoid alkaloids from the seeds of Nigella glandulifera Freyn (Ranunculaceae) exhibited protein of tyrosine phosphatase 1B (PTP1B) inhibitory activity in vitro. In the present study, we further investigated their anti-diabetes activities in L6 moytubes and illuminated the mechanisms of action of compounds A-C. Several parameters of glucose metabolism such as glucose consumption, glycogen content and hexokinase activity were increased by compounds A-C...
December 31, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28048289/su-f-t-678-clotrimazole-sensitizes-mcf-7-breast-cancer-cell-line-to-radiation
#9
L Garcia, M Tambasco
PURPOSE: To study the effects of Clotrimazole (CLT) on radiosensitivity of MCF-7 Cells in correlation to detachment of Hexokinase II from the Voltage Dependent Anion Channel on the outer membrane of the mitochondria. Apoptotic fractions were also analyzed in relation to the detachment of Hexokinase. METHODS: This study focused on the mammary adenocarcinoma cell line, MCF-7. Colony forming assays were used to analyze radiosensitization by CLT. Flow cytometry methods were used to analyze apoptotic vs necrotic fractions after treatment with CLT...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28046212/su-f-t-677-synergistic-effect-s-of-clotrimazole-on-radiation-cell-survival-of-a549-lung-cancer-cells-in-glucose-vs-galactose-media
#10
G Boss, M Tambasco, M Garakani
PURPOSE: In order to determine the synergistic effect of clotrimazole on radiosensitivity of A549 lung cancer cells, and the effect of oxidative pathways on modulating radiosensitivity, we studied how these cells survived under varying amounts of radiation and clotrimazole as well ass when glucose was switched for galactose media. METHODS: The glucose media was used to determine the presence of any synergistic effect of clotrimazole on radiation using values of radiation and clotrimazole concentrations, varying from 0 - 8 Gy and 0 - 20 µM, respectively...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28043795/evaluation-of-substituted-ebselen-derivatives-as-potential-trypanocidal-agents
#11
Heeren M Gordhan, Stephen L Patrick, Maria I Swasy, Amber L Hackler, Mark Anayee, Jennifer E Golden, James C Morris, Daniel C Whitehead
Human African trypanosomiasis is a disease of sub-Saharan Africa, where millions are at risk for the illness. The disease, commonly referred to as African sleeping sickness, is caused by an infection by the eukaryotic pathogen, Trypanosoma brucei. Previously, a target-based high throughput screen revealed ebselen (EbSe), and its sulfur analog, EbS, to be potent in vitro inhibitors of the T. brucei hexokinase 1 (TbHK1). These molecules also exhibited potent trypanocidal activity in vivo. In this manuscript, we synthesized a series of sixteen EbSe and EbS derivatives bearing electron-withdrawing carboxylic acid and methyl ester functional groups, and evaluated the influence of these substituents on the biological efficacy of the parent scaffold...
December 10, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28042874/in-vitro-assessment-of-the-glucose-lowering-effects-of-berberrubine-9-o-%C3%AE-d-glucuronide-an-active-metabolite-of-berberrubine
#12
Na Yang, Run-Bin Sun, Xing-Long Chen, Le Zhen, Chun Ge, Yu-Qing Zhao, Jun He, Jian-Liang Geng, Jia-Hua Guo, Xiao-Yi Yu, Fei Fei, Si-Qi Feng, Xuan-Xuan Zhu, Hong-Bo Wang, Feng-Hua Fu, Ji-Ye Aa, Guang-Ji Wang
Berberrubine (BRB) is the primary metabolite of berberine (BBR) that has shown a stronger glucose-lowering effect than BBR in vivo. On the other hand, BRB is quickly and extensively metabolized into berberrubine-9-O-β-D-glucuronide (BRBG) in rats after oral administration. In this study we compared the pharmacokinetic properties of BRB and BRBG in rats, and explored the mechanisms underlying their glucose-lowering activities. C57BL/6 mice with HFD-induced hyperglycemia were administered BRB (50 mg·kg(-1)·d(-1), ig) for 6 weeks, which caused greater reduction in the plasma glucose levels than those caused by BBR (120 mg·kg(-1)·d(-1)) or BRB (25 mg·kg(-1)·d(-1))...
January 2, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28028442/regulation-of-vdac-trafficking-modulates-cell-death
#13
Ashvini K Dubey, Ashwini Godbole, M K Mathew
The voltage-dependent anion channel (VDAC) and mitochondria-associated hexokinase (HxK) have crucial roles in both cell survival and death. Both the individual abundances and their ratio seem to influence the balance of survival and death and are thus critical in scenarios, such as neurodegeneration and cancer. Elevated levels of both VDAC and HxK have been reported in cancerous cells. Physical interaction is surmised and specific residues or regions involved have been identified, but details of the interaction and the mechanism by which it modulates survival are yet to be elucidated...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/28025803/metabolic-transition-of-milk-lactose-synthesis-and-up-regulation-by-akt1-in-sows-from-late-pregnancy-to-lactation
#14
Fang Chen, Baoliang Chen, Wutai Guan, Jun Chen, Yantao Lv, Hanzhen Qiao, Chaoxian Wang, Yinzhi Zhang
Lactose plays a crucial role in controlling milk volume by inducing water toward into the mammary secretory vesicles from the mammary epithelial cell cytoplasm, thereby maintaining osmolality. In current study, we determined the expression of several lactose synthesis related genes, including glucose transporters (glucose transporter 1, glucose transporter 8, sodium-glucose cotransporter 1, sodium-glucose cotransporter 3, and sodium-glucose cotransporter 5), lactose synthases (α-lactalbumin and β1,4-galactosyltransferase), and hexokinases (hexokinase-1 and hexokinase-2) in sow mammary gland tissue at day 17 before delivery, on the 1st day of lactation and at peak lactation...
December 26, 2016: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28025745/microrna-98-suppress-warburg-effect-by-targeting-hk2-in-colon-cancer-cells
#15
Weimin Zhu, Yijiao Huang, Qi Pan, Pei Xiang, Nanlan Xie, Hao Yu
BACKGROUND: Warburg effect is a hallmark of cancer cells. Accumulating evidence suggests that microRNAs (miRs) could regulate such metabolic reprograming. Aberrant expression of miR-98 has been observed in many types of cancers. However, its functions and significance in colon cancer remain largely elusive. AIMS: To investigate miR-98 expression and the biological functions in colon cancer progression. METHODS: miR-98 expression levels were determined by quantitative RT-PCR in 215 cases of colon cancer samples...
December 26, 2016: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28013175/isolation-and-expression-features-of-hexose-kinase-genes-under-various-abiotic-stresses-in-the-tea-plant-camellia-sinensis
#16
Na-Na Li, Wen-Jun Qian, Lu Wang, Hong-Li Cao, Xin-Yuan Hao, Ya-Jun Yang, Xin-Chao Wang
Hexokinases (HXKs, EC 2.7.1.1) and fructokinases (FRKs, EC 2.7.1.4) play important roles in carbohydrate metabolism and sugar signaling during the growth and development of plants. However, the HXKs and FRKs in the tea plant (Camellia sinensis) remain largely unknown. In this manuscript, we present the molecular characterization, phylogenetic relationships, conserved domains and expression profiles of four HXK and seven FRK genes of the tea plant. The 11 deduced CsHXK and CsFRK proteins were grouped into six main classes...
November 25, 2016: Journal of Plant Physiology
https://www.readbyqxmd.com/read/28012288/peach-leaf-curl-disease-shifts-sugar-metabolism-in-severely-infected-leaves-from-source-to-sink
#17
Stefano Moscatello, Simona Proietti, Roberto Buonaurio, Franco Famiani, Vittorio Raggi, Robert P Walker, Alberto Battistelli
Peach leaf curl is a disease that affects the leaves of peach trees, and in severe cases all of the leaf can be similarly affected. This study investigated some effects of this disease on the metabolism of peach leaves in which all parts of the leaf were infected. These diseased leaves contained very little chlorophyll and performed little or no photosynthesis. Compared to uninfected leaves, diseased leaves possessed higher contents of fructose and especially glucose, but lowered contents of sucrose, sorbitol and especially starch...
December 1, 2016: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28002512/pharmacotoxicological-screening-on-new-derivatives-of-beta-phenylethylamine-potential-agonists-of-beta3-adrenergic-receptors
#18
Simona Negreş, Anca Zanfirescu, Floriana Elvira Ionică, Elena Moroşan, Bruno Ştefan Velescu, Oana Cristina Şeremet, Cristina Elena Zbârcea, Emil Ştefănescu, Manuella Militaru, Andreea LetiŢia Arsene, Denisa Marilena Margină, Livia Uncu, Corina Scutari, Cornel ChiriŢă
BACKGROUND AND AIMS: Beta3-adrenergic receptors (beta3-ARs) have been initially characterized in 1989. Afterwards, their tissue distribution was established: white and brown adipose tissue, central nervous system, myocardium (atrial and ventricular), blood vessels, smooth gastrointestinal muscles (stomach, small intestine, colon), gallbladder, urinary bladder, prostate, skeletal muscles. Non-clinical trials have demonstrated the major implication of beta3-ARs in glucose metabolism, implicitly, in insulin release, and also in obesity...
2016: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/27989634/heterologous-expression-of-paranosema-antonospora-locustae-hexokinase-in-lepidopteran-sf9-cells-is-followed-by-accumulation-of-the-microsporidian-protein-in-insect-cell-nuclei
#19
Sergey A Timofeev, Igor V Senderskiy, Alexander A Tsarev, Yuri S Tokarev, Viacheslav V Dolgikh
Paranosema (Nosema, Antonospora) locustae is the only microsporidium produced as a commercial product for biological control. Molecular mechanisms of the effects of this pathogen and other invertebrate microsporidia on host cells remain uncharacterized. Previously, we immunolocalized P. locustae hexokinase in nuclei of Locusta migratoria infected adipocytes. Here, the microsporidian protein was expressed in the yeast Pichia pastoris and in lepidopteran Sf9 cells. During heterologous expression, P. locustae hexokinase was accumulated in the nuclei of insect cells but not in yeast cell nuclei...
December 16, 2016: Journal of Invertebrate Pathology
https://www.readbyqxmd.com/read/27983708/the-hk2-dependent-warburg-effect-and-mitochondrial-oxidative-phosphorylation-in-cancer-targets-for-effective-therapy-with-3-bromopyruvate
#20
REVIEW
Paweł Lis, Mariusz Dyląg, Katarzyna Niedźwiecka, Young H Ko, Peter L Pedersen, Andre Goffeau, Stanisław Ułaszewski
This review summarizes the current state of knowledge about the metabolism of cancer cells, especially with respect to the "Warburg" and "Crabtree" effects. This work also summarizes two key discoveries, one of which relates to hexokinase-2 (HK2), a major player in both the "Warburg effect" and cancer cell immortalization. The second discovery relates to the finding that cancer cells, unlike normal cells, derive as much as 60% of their ATP from glycolysis via the "Warburg effect", and the remaining 40% is derived from mitochondrial oxidative phosphorylation...
December 15, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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