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Hexokinase 2

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https://www.readbyqxmd.com/read/29334666/effects-of-berberine-chloride-on-the-liver-of-streptozotocin-induced-diabetes-in-albino-wistar-rats
#1
Govindasami Chandirasegaran, Chakkaravarthy Elanchezhiyan, Kavisa Ghosh
The goal of the present study is to evaluate the effect of Berberine chloride (BC) on the liver of streptozotocin (STZ) induced diabetic rat. Diabetic rats were treated with BC (50 mg/kg b.w) or glibenclamide (6 mg/kg b.w), daily for 45 days. After BC treatment in diabetic rats, there was a significant (P < 0.05) decline in the levels of hepatic markers, lipid peroxidation markers such as lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARS), and pro-inflammatory mediators like tumor necrosis factor-alpha (TNF-α), phosphorylated nuclear factor kappa-B-p65 (phospho-NF-κB p65), cyclooxygenase (COX-2), nitric oxide synthase (iNOS) as well as pro-apoptotic mediators such as Bax and cytochrome c...
January 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29318370/the-metabolism-and-transport-of-1-5-anhydroglucitol-in-cells
#2
Lingwen Ying, Xiaojing Ma, Jun Yin, Yufei Wang, Xingxing He, Jiahui Peng, Yuqian Bao, Jian Zhou, Weiping Jia
AIMS: Our previous studies demonstrated that serum 1,5-anhydroglucitol (1,5-AG) levels increased slightly rather than declined after an acute glucose load. Therefore, the current study aims at exploring the transport and metabolic characteristics of 1,5-AG, as well as the effect of glucose on 1,5-AG transport. METHODS: Km and Vmax were determined to measure the affinity of glucose oxidase (GOD) and hexokinase (HK) for 1,5-AG and glucose. HepG2, C2C12, and primary mouse hepatocytes were incubated for 2 h with 1,5-AG at concentrations of 0, 80, and 160 μg/mL...
January 9, 2018: Acta Diabetologica
https://www.readbyqxmd.com/read/29305912/new-natural-inhibitors-of-hexokinase-2-hk2-steroids-from-ganoderma-sinense
#3
Fengyan Bao, Kaiyin Yang, Canrong Wu, Suyu Gao, Penghe Wang, Lixia Chen, Hua Li
Hexokinase 2 (HK2), a rate-limiting enzyme in the first step of glycolysis pathway, expresses at high level in cancer cells compared with normal cells. HK2 provides a new target for cancer therapy due to its pivotal role in tumor tumourigenic and metastatic process. The structure-based virtual ligand screening in a small in-house database of natural products predicted that a new steroid, (22E,24R)-6β-methoxyergosta-7,9(11),22-triene-3β,5α-diol (2) from Ganoderma sinense has high binding affinity to HK2 with significant calculated binding free energy...
January 3, 2018: Fitoterapia
https://www.readbyqxmd.com/read/29298880/the-catalytic-inactivation-of-the-n-half-of-human-hexokinase-2-and-structural-and-biochemical-characterization-of-its-mitochondrial-conformation
#4
Mir Hussain Nawaz, Juliana C Ferreira, Lyudmila Nedyalkova, Haizhong Zhu, César Carrasco-López, Serdal Kirmizialtin, Wael M Rabeh
The high proliferation rate of tumor cells demands high energy and metabolites that are sustained by a high glycolytic flux known as the "Warburg effect". The activation and further metabolism of glucose is initiated by hexokinase, a focal point of metabolic regulation. The human hexokinase 2 (HK2) is overexpressed in all aggressive tumors and predominantly found on the mitochondria, where interactions through its N-terminus initiates and maintains tumorigenesis. Here, we report the structure of HK2 in complex with glucose and glucose 6-phosphate...
January 3, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29298131/a-systematic-review-of-p53-regulation-of-oxidative-stress-in-skeletal-muscle
#5
Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
January 3, 2018: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/29291405/enhanced-glycometabolism-as-a-mechanism-of-nqo1-potentiated-growth-of-nsclc-revealed-by-metabolomic-profiling
#6
Xuefang Cheng, Fang Liu, Huiying Liu, Guangji Wang, Haiping Hao
NAD(P)H:quinone oxidoreductase 1 (NQO1), a cytoplasmic 2-electron reductase, has been considered as a potential poor prognostic biomarker and a promising therapeutic target for patients with non-small cell lung cancer (NSCLC) due to its frequent overexpression and significantly increased activity in NSCLC. Previous studies have shown that depleting tumor-NQO1 potentiates anoikis and inhibits growth of NSCLC. However, the underlying mechanisms whereby NQO1 potentiates proliferation have not been fully understood...
December 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29290953/viral-e6-e7-oncogene-and-cellular-hexokinase-2-expression-in-hpv-positive-cancer-cell-lines
#7
Karin Hoppe-Seyler, Anja Honegger, Felicitas Bossler, Jasmin Sponagel, Julia Bulkescher, Claudia Lohrey, Felix Hoppe-Seyler
Oncogenic types of human papillomaviruses (HPVs) are major human carcinogens. Cancer cells typically exhibit metabolic alterations which support their malignant growth. These include an enhanced rate of aerobic glycolysis ('Warburg effect') which in cancer cells is often linked to an increased expression of the rate-limiting glycolytic enzyme Hexokinase 2 (HK2). Intriguingly, recent studies indicate that the HPV E6/E7 oncogenes cause the metabolic reprogramming in HPV-positive cancer cells by directly upregulating HK2 expression...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29287724/paris-reprograms-glucose-metabolism-by-hif-1%C3%AE-induction-in-dopaminergic-neurodegeneration
#8
Hojin Kang, Areum Jo, Hyein Kim, Rin Khang, Ji-Yeong Lee, Hanna Kim, Chi-Hu Park, Jeong-Yun Choi, Yunjong Lee, Joo-Ho Shin
Our previous study found that PARIS (ZNF746) transcriptionally suppressed transketolase (TKT), a key enzyme in pentose phosphate pathway (PPP) in the substantia nigra (SN) of AAV-PARIS injected mice. In this study, we revealed that PARIS overexpression reprogrammed glucose metabolic pathway, leading to the increment of glycolytic proteins along with TKT reduction in the SN of AAV-PARIS injected mice. Knock-down of TKT in differentiated SH-SY5Y cells led to an increase of glycolytic enzymes and decrease of PPP-related enzymes whereas overexpression of TKT restored PARIS-mediated glucose metabolic shift, suggesting that glucose metabolic alteration by PARIS is TKT-dependent...
December 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29286170/licochalcone-a-suppresses-hexokinase-2-mediated-tumor-glycolysis-in-gastric-cancer-via-downregulation-of-the-akt-signaling-pathway
#9
Jian Wu, Xingxing Zhang, Yaohui Wang, Qingmin Sun, Min Chen, Shenlin Liu, Xi Zou
Licochalcone A (LicA) is a chalcone extracted from liquorice which has been used as a traditional Chinese medicine for many generations. Increased glucose consumption and glycolytic activity are important hallmarks of cancer cells, and hexokinase 2 (HK2) upregulation is a major contributor to the elevation of glycolysis. Recently, the antitumor activities of LicA have been reported in various cancers; however, its effect on tumor glycolysis in gastric cancer and the underlying mechanisms are completely unknown...
December 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29285270/metformin-alleviates-nickel-induced-autophagy-and-apoptosis-via-inhibition-of-hexokinase-2-activating-lipocalin-2-in-human-bronchial-epithelial-cells
#10
Yu-Ting Kang, Wen-Cheng Hsu, Chih-Hsien Wu, I-Lun Hsin, Pei-Ru Wu, Kun-Tu Yeh, Jiunn-Liang Ko
Autophagy is an intracellular recycling and degradation process for regulating tumor progression, survival and drug resistance. Nickel compounds have been identified as human carcinogens. However, the role of nickel-induced autophagy in lung carcinogenesis has not yet been fully elucidated. In this study, we determined that hexokinase 2 (HK2), which phosphorylates glucose and regulates autophagy, is the key mediator in nickel-induced autophagy in lung bronchial epithelial cells. We attempted to investigate the effects of the antidiabetic drug metformin on HK2 expression and lung cancer chemoprevention...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29258429/mesenchymal-stem-cell-conditioned-medium-alleviates-oxidative-stress-injury-induced-by-hydrogen-peroxide-via-regulating-mir143-and-its-target-protein-in-hepatocytes
#11
Xuejing Xu, Dong Li, Xue Li, Qing Shi, Xiuli Ju
BACKGROUND: To investigate the impact of miRNA (microRNA) on hepatic oxidative stress damage under the human mesenchymal stem cell conditioned medium (MSC-CM) and explore the roles of the beta-1 adrenergic receptor (ADRB1) and hexokinase 2 (HK2) in this process. METHODS: Hydrogen peroxide was used to induce oxidative stress injury in the human normal liver cell line L02. MSC-CM was separately prepared. After treatment with MSC-CM, the protective effects of MSC-CM on oxidative stress injury were assessed by changes in apoptosis, cell viability, cell cycle, and mitochondrial membrane potential...
December 19, 2017: BMC Immunology
https://www.readbyqxmd.com/read/29247727/comparative-investigation-for-hypoglycemic-effects-of-polysaccharides-from-four-substitutes-of-lonicera-japonica-in-chinese-medicine
#12
Xiangmei Zhao, Dongying Wang, Lijie Qin, Xianzhi Yang, Chuanyu Gao
The polysaccharide fractions were obtained from flower buds of the four substitutes of Lonicera japonica, L. macranthoides (LMPB), L. hypoglauca (LHPB), L. fulvotomentosa (LFPB) and L. confuse (LCPB), and their hypoglycemic effects were investigated. In study, streptozocin (STZ)-induced diabetic rats were orally administrated once daily with LMPB, LHPB, LFPB and LCPB (each 800 mg/kg) for 42 days. Reduction for food and water intake (p < 0.05, p < 0.01) and levels of sugar and insulin (p < 0...
December 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29247711/hexokinase-2-confers-resistance-to-cisplatin-in-ovarian-cancer-cells-by-enhancing-cisplatin-induced-autophagy
#13
Xiao-Yan Zhang, Meng Zhang, Qing Cong, Ming-Xing Zhang, Meng-Yu Zhang, Ying-Ying Lu, Cong-Jian Xu
The high mortality rate of ovarian cancer is connected with the development of acquired resistance to multiple cancer drugs, especially cisplatin. Activation of cytoprotective autophagy has been implicated as a contributing mechanism for acquired cisplatin resistance in ovarian cancer cells. Hexokinase 2 (HK2) phosphorylates glucose to generate glucose-6-phosphate, the rate-limiting step in glycolysis. Higher HK2 expression has been associated with chemoresistance in ovarian cancer. However, whether HK2 functionally contributes to cisplatin resistance in ovarian cancer is unclear...
December 13, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29225201/3-bromopyruvate-as-a-potential-pharmaceutical-in-the-light-of-experimental-data
#14
Izabela Szczuka, Andrzej Gamian, Grzegorz Terlecki
3-Bromopyruvate (3-BrPA) is an halogenated analogue of pyruvic acid known for over four decades as an alkylating agent reacting with thiol groups of many proteins. It enters animal cells like a lactate: via monocarboxylic acid transporters. Increasing interest in this compound, in recent times, is mainly due to hopes associated with its anticancer action. It is based on the impairment of energy metabolism of tumor cells by inhibiting enzymes in the glycolysis pathway (hexokinase II, glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate kinase) and the oxidative phosphorylation (succinate dehydrogenase)...
December 8, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/29220380/hexokinase-2-hk2-the-tumor-promoter-in-glioma-is-downregulated-by-mir-218-bmi1-pathway
#15
Hui Liu, Nan Liu, Yingduan Cheng, Weilin Jin, Pengxing Zhang, Xin Wang, Hongwei Yang, Xiaoshan Xu, Zhen Wang, Yanyang Tu
In cancer, glycolysis driving enzymes and their regulating microRNAs are one of the key focus of oncology research lately. The glycolytic enzyme hexokinase 2 (HK2) is crucial for the Warburg effect in human glioma, the most common malignant brain tumor. In the present study, we studied the tumorigenic role of HK2 in glioma, and clarified the mechanism of miR-218 induced HK2 regulation in glioma development. The HK2 expression in patient derived glioma and non neoplastic brain tissue was quantified. The HK2 silenced U87 and U251 cell lines were assessed for their proliferation, migration and invasive potential in vitro, while the tumor forming potential of U87 cells was evaluated in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/29212451/a-small-pancreatic-hamartoma-with-an-obstruction-of-the-main-pancreatic-duct-and-avid-fdg-uptake-mimicking-a-malignant-pancreatic-tumor-a-systematic-case-review
#16
Hiroaki Nagano, Masayuki Nakajo, Yoshihiko Fukukura, Yoriko Kajiya, Atsushi Tani, Sadao Tanaka, Mari Toyota, Toru Niihara, Masaki Kitazono, Toyokuni Suenaga, Takashi Yoshiura
BACKGROUND: Pancreatic hamartomas are extremely rare and may be misdiagnosed as malignant tumors. We report herein a case of a small, solid-type pancreatic hamartoma. CASE PRESENTATION: A 72-year-old female was incidentally detected pancreatic lesion by ultrasonography. Computed tomography and magnetic resonance imaging revealed a 2.0-cm solid lesion. The main pancreatic duct (MPD) was obstructed by the lesion in the head of the pancreas, and the upstream MPD was dilated...
December 6, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/29207019/stromal-epithelial-lactate-shuttle-induced-by-tumor%C3%A2-derived-interleukin%C3%A2-1%C3%AE-promotes-cell-proliferation-in-oral-squamous-cell-carcinoma
#17
Jie Wu, Yun Hong, Tong Wu, Juan Wang, Xiaobing Chen, Zhi Wang, Bin Cheng, Juan Xia
Stromal-epithelial lactate shuttle is an essential process to support fast‑growing tumor cells, however, the underlying mechanism remains ambiguous. Interleukin‑1β (IL‑1β), which is a key node gene in both stromal and epithelial cells of oral squamous cell carcinoma (OSCC), may participate in this metabolic reprogramming. In the present study, anaerobic glycolysis of cancer‑associated fibroblasts (CAFs) was evaluated and the role of IL‑1β in regulating stromal‑epithelial lactate shuttle was determined...
November 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29205357/hexokinase-2-dependent-hyperglycolysis-driving-microglial-activation-contributes-to-ischemic-brain-injury
#18
Yuan Li, Bingzheng Lu, Longxiang Sheng, Zhu Zhu, Hongjiaqi Sun, Yuwei Zhou, Yang Yang, Dongdong Xue, Wenli Chen, Xuyan Tian, Yun Du, Min Yan, Wenbo Zhu, Fan Xing, Kai Li, Suizhen Lin, Pengxin Qiu, Xingwen Su, Yijun Huang, Guangmei Yan, Wei Yin
Hyperglycolysis, observed within the penumbra zone during brain ischemia, was shown to be detrimental for tissue survival due to lactate accumulation and reactive oxygen species (ROS) overproduction in clinical and experimental settings. Recently, mounting evidence suggests that glycolytic reprogramming and induced metabolic enzymes can fuel the activation of peripheral immune cells. However, the possible roles and details regarding hyperglycolysis in neuroinflammation during ischemia are relatively poorly understood...
December 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29203613/nfe2l1-silenced-insulinoma-cells-acquire-aggressiveness-and-chemo-resistance
#19
Jingqi Fu, Hongzhi Zheng, Qi Cui, Chengjie Chen, Simeng Bao, Jing Sun, Lu Li, Bei Yang, Huihui Wang, Yongyong Hou, Yuanyuan Xu, Yuanhong Xu, Qiang Zhang, Jingbo Pi
The transcription factor nuclear factor erythroid 2 like 1 (NFE2L1 or NRF1) is involved in various critical cell processes such as maintenance of ubiquitin-proteasome system and regulation of the cellular antioxidant response. We previously determined that pancreatic β-cell-specific Nfe2l1-knockout mice had hyperinsulinemia, and that silencing of Nfe2l1 in mouse islets or MIN6 insulinoma β-cells induced elevated basal insulin release and altered glucose metabolism. Hypoglycemia is a major issue with aggressive insulinomas, although a role of NFE2L1 in this pathology is not defined...
December 4, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29187279/upstream-signalling-of-mtorc1-and-its-hyperactivation-in-type-2-diabetes-t2d
#20
Muhammad Ali, Shazia Anwer Bukhari, Muhammad Ali, Han-Woong Lee
Mammalian target of rapamycin complex 1 (mTORC1) plays a major role in cell growth, proliferation, polarity, differentiation, development, and controls transitioning between anabolic and catabolic states of the cell. It collects almost all extracellular and intracellular signals from growth factors, nutrients, and maintains cellular homeostasis, and is involved in several pathological conditions including, neurodegeneration, Type 2 diabetes (T2D), obesity, and cancer. In this review, we summarize current knowledge of upstream signaling of mTORC1 to explain etiology of T2D and hypertriglyceridemia, in which state, the role of telomere attrition is explained...
October 30, 2017: BMB Reports
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