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Henry H Nguyen, Abdel Aziz Shaheen, Natalia Baeza, Ellina Lytvyak, Stefan J Urbanski, Andrew L Mason, Gary L Norman, Marvin J Fritzler, Mark G Swain
BACKGROUND AND AIMS: Up to 20% of Primary Biliary Cholangitis (PBC) patients are estimated to have features that overlap with Autoimmune Hepatitis (AIH). Patients with PBC-AIH overlap syndrome (PBC-AIH OS) have been reported to exhibit suboptimal responses to ursodeoxycholic acid therapy, and are more likely to progress to cirrhosis. Anti-double stranded DNA (anti-dsDNA) and anti-p53 have been previously suggested to be potential autoantibodies for identifying patients with PBC-AIH OS...
2018: PloS One
Haohua Wang, Roujun Peng, Xiuxing Chen, Rui Jia, Chunyue Huang, Yuanyuan Huang, Liangping Xia, Guifang Guo
Although hexokinase (HK) 2, pyruvate kinase muscle (PKM) isozyme 2 and lactate dehydrogenase (LDH) A predict the efficacy of medicines in various solid tumors, their ability to predict the efficacy of cetuximab in metastatic colorectal cancer (mCRC) remains unclear. mCRC patients with pathological specimens who received cetuximab and chemotherapy from 2005 to 2015 in the present institution were enrolled. Immunohistochemistry was used to detect HK2, PKM2 and LDHA expression. SPSS20 was used for statistical analysis...
April 2018: Oncology Letters
Krishna B Singh, Eun-Ryeong Hahm, Lora H Rigatti, Daniel P Normolle, Jian-Min Yuan, Shivendra V Singh
We have shown previously that dietary administration of phenethyl isothiocyanate (PEITC), a small molecule from edible cruciferous vegetables, significantly decreases the incidence of poorly-differentiated prostate cancer in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice without any side effects. In this study, we investigated the role of c-Myc-regulated glycolysis in prostate cancer chemoprevention by PEITC. Exposure of LNCaP (androgen-responsive) and 22Rv1 (castration-resistant) human prostate cancer cells to PEITC resulted in suppression of expression as well as transcriptional activity of c-Myc...
March 15, 2018: Cancer Prevention Research
Jun-Ho Cho, Goo-Young Kim, Brian C Mansfield, Janice Y Chou
Glycogen storage disease type Ia (GSD-Ia) is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC), a key enzyme in endogenous glucose production. This autosomal recessive disorder is characterized by impaired glucose homeostasis and long-term complications of hepatocellular adenoma/carcinoma (HCA/HCC). We have shown that hepatic G6Pase-α deficiency-mediated steatosis leads to defective autophagy that is frequently associated with carcinogenesis. We now show that hepatic G6Pase-α deficiency also leads to enhancement of hepatic glycolysis and hexose monophosphate shunt (HMS) that can contribute to hepatocarcinogenesis...
March 12, 2018: Biochemical and Biophysical Research Communications
Glenn R Bantug, Marco Fischer, Jasmin Grählert, Maria L Balmer, Gunhild Unterstab, Leyla Develioglu, Rebekah Steiner, Lianjun Zhang, Ana S H Costa, Patrick M Gubser, Anne-Valérie Burgener, Ursula Sauder, Jordan Löliger, Réka Belle, Sarah Dimeloe, Jonas Lötscher, Annaïse Jauch, Mike Recher, Gideon Hönger, Michael N Hall, Pedro Romero, Christian Frezza, Christoph Hess
Glycolysis is linked to the rapid response of memory CD8+ T cells, but the molecular and subcellular structural elements enabling enhanced glucose metabolism in nascent activated memory CD8+ T cells are unknown. We found that rapid activation of protein kinase B (PKB or AKT) by mammalian target of rapamycin complex 2 (mTORC2) led to inhibition of glycogen synthase kinase 3β (GSK3β) at mitochondria-endoplasmic reticulum (ER) junctions. This enabled recruitment of hexokinase I (HK-I) to the voltage-dependent anion channel (VDAC) on mitochondria...
March 1, 2018: Immunity
Maia Kavanagh Williamson, Naomi Coombes, Florian Juszczak, Marios Athanasopoulos, Mariam B Khan, Thomas R Eykyn, Ushani Srenathan, Leonie S Taams, Julianna Dias Zeidler, Andrea T Da Poian, Hendrik Huthoff
Infection of primary CD4+ T cells with HIV-1 coincides with an increase in glycolysis. We investigated the expression of glucose transporters (GLUT) and glycolytic enzymes in human CD4+ T cells in response to infection with HIV-1. We demonstrate the co-expression of GLUT1, GLUT3, GLUT4, and GLUT6 in human CD4+ T cells after activation, and their concerted overexpression in HIV-1 infected cells. The investigation of glycolytic enzymes demonstrated activation-dependent expression of hexokinases HK1 and HK2 in human CD4+ T cells, and a highly significant increase in cellular hexokinase enzyme activity in response to infection with HIV-1...
March 7, 2018: Viruses
Zengpeng Lv, Hao Fan, Beibei Zhang, Chao Ning, Kun Xing, Yuming Guo
Genistein (GEN) is a type of isoflavone mainly derived from soy products. In this experiment, we added 40 and 400 mg/kg GEN to the diet of laying broiler breeder hens to clarify the maternal effects of GEN on the development and metabolism of chick embryos. GEN treatment at 40 mg/kg increased embryonic length, weight, and liver index, as well as the width of the proliferative zone in the tibial growth plate of chick embryos. Gene ontology (GO) cluster analysis of the hepatic transcriptome showed that GEN treatment promoted embryonic development and cell proliferation...
March 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Minglin Pan, Ying Han, Aninda Basu, Anzhi Dai, Rui Si, Conor Willson, Angela Balistrieri, Brian T Scott, Ayako Makino
Coronary microvascular rarefaction due to endothelial cell (EC) dysfunction is one of the causes of increased morbidity and mortality in diabetes. Coronary ECs in diabetes are more apoptotic due partly to mitochondrial calcium overload. This study was designed to investigate the role of hexokinase 2 (HK2, an endogenous inhibitor of voltage-dependent anion channel) in coronary endothelial dysfunction in type 2 diabetes. We used mouse coronary ECs (MCECs) isolated from type 2 diabetic mice and human coronary ECs (HCECs) from type 2 diabetic patients to examine protein levels and mitochondrial functions...
March 7, 2018: American Journal of Physiology. Cell Physiology
Theodoros Eleftheriadis, Georgios Pissas, Vassilios Liakopoulos, Ioannis Stefanidis
Indoleamine 2, 3-dioxygenase (IDO) suppresses T-cell function at least in part by altering cell metabolism. Hypoxia-inducible factor-1 (HIF-1) increases upon T-cell activation and alters cell metabolism favoring their differentiation to effector cells. The effect of IDO on HIF-1α expression and activity was evaluated. For this purpose, mixed lymphocyte reaction (MLR) was performed using the IDO inhibitor 1-DL-methyl-tryptophan and the p53 inhibitor pifithrin-α. L-tryptophan degradation and cell proliferation were assessed by enzyme-linked immunosorbent assay, whereas the expression of proteins of interest by western blotting...
February 2018: Iranian Journal of Allergy, Asthma, and Immunology
Sarah Morar Schneider, Vidya Sridhar, Amanda K Bettis, Heather Heath-Barnett, Cynthia J Balog-Alvarez, Lee-Jae Guo, Rachel Johnson, Scott Jaques, Stanislav Vitha, Alan C Glowcwski, Joe N Kornegay, Peter P Nghiem
PURPOSE: Metabolic dysfunction in Duchenne muscular dystrophy (DMD) is characterized by reduced glycolytic and oxidative enzymes, decreased and abnormal mitochondria, decreased ATP, and increased oxidative stress. We analyzed glucose metabolism as a potential disease biomarker in the genetically homologous golden retriever muscular dystrophy (GRMD) dog with molecular, biochemical, and in vivo imaging. PROCEDURES: Pelvic limb skeletal muscle and left ventricle tissue from the heart were analyzed by mRNA profiling, qPCR, western blotting, and immunofluorescence microscopy for the primary glucose transporter (GLUT4)...
March 5, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Debora Vignali, Elisa Cantarelli, Carlotta Bordignon, Adriana Canu, Antonio Citro, Andrea Annoni, Lorenzo Piemonti, Paolo Monti
Stem memory T cells (Tscm) constitute the earliest developmental stage of memory T cells, displaying stem cell-like properties such as self-renewal capacity. Their superior immune reconstitution potential has sparked interest in cancer immune-therapy, vaccine development and immune reconstitution, whereas their role in autoimmunity is largely unexplored. Here we show that autoreactive CD8+ Tscm specific for β cell antigens GAD65, insulin and IGRP are present in patients with type 1 diabetes (T1D). In vitro, generation of autoreactive Tscm from naïve precursors required the presence of the homeostatic cytokine interleukin-7 (IL-7)...
March 5, 2018: Diabetes
Yanyan Wang, Xueting Han, Mingqiang Fu, Jingfeng Wang, Yu Song, Yuan Liu, Jingjing Zhang, Jingmin Zhou, Junbo Ge
Protection of cardiac microvascular endothelial cells (CMECs) against hypoxia injury is an important therapeutic strategy for treating ischaemic cardiovascular disease. In this study, we investigated the effects of qiliqiangxin (QL) on primary rat CMECs exposed to hypoxia and the underlying mechanisms. Rat CMECs were successfully isolated and passaged to the second generation. CMECs that were pre-treated with QL (0.5 mg/mL) and/or HIF-1α siRNA were cultured in a three-gas hypoxic incubator chamber (5% CO2 , 1% O2 , 94% N2 ) for 12 hours...
March 4, 2018: Journal of Cellular and Molecular Medicine
Zongdong Li, Natasha M Nesbitt, Lisa E Malone, Dimitri V Gnatenko, Song Wu, Daifeng Wang, Wei Zhu, Geoffrey D Girnun, Wadie F Bahou
Bioenergetic requirements of hematopoietic stem cells (HSC) and pluripotent stem cells (PSC) vary with lineage fate, and cellular adaptations rely largely on substrate (glucose/glutamine) availability and mitochondrial function to balance TCA-derived anabolic and redox-regulated antioxidant functions.  Heme synthesis and degradation converge in a linear pathway that utilizes TCA cycle-derived carbon in cataplerotic reactions of tetrapyrrole biosynthesis, terminated by NAD(P)H-dependent biliverdin reductases (IXα, BLVRA and IXβ, BLVRB) that lead to bilirubin generation and cellular antioxidant functions...
March 2, 2018: Biochemical Journal
Courtney R Sullivan, Rachael H Koene, Kathryn Hasselfeld, Sinead M O'Donovan, Amy Ramsey, Robert E McCullumsmith
Schizophrenia is a devastating illness that affects over 2 million people in the United States and costs society billions of dollars annually. New insights into the pathophysiology of schizophrenia are needed to provide the conceptual framework to facilitate development of new treatment strategies. We examined bioenergetic pathways in the dorsolateral prefrontal cortex (DLPFC) of subjects with schizophrenia and control subjects using western blot analysis, quantitative real-time polymerase chain reaction, and enzyme/substrate assays...
March 1, 2018: Molecular Psychiatry
Chia-Lin Wu, Ching-Ching Chang, Jie-Kai Wu, Meng-Hsuan Chiang, Chu-Huai Yang, Hsueh-Cheng Chiang
Glucose catabolism, also known as glycolysis, is important for energy generation and involves a sequence of enzymatic reactions that convert a glucose molecule into two pyruvate molecules. The glycolysis process generates adenosine triphosphate as a byproduct. In this study, we investigated whether glycolysis plays a role in maintaining neuronal functions in the Drosophila mushroom bodies (MBs), which are generally accepted to be an olfactory learning and memory center. Our data showed that individual knockdown of glycolytic enzymes in the MBs, including hexokinase (HexA), phosphofructokinase (Pfk), or pyruvate kinase (PyK), disrupts olfactory memory...
February 22, 2018: Neurobiology of Learning and Memory
Marine Fuhrmann, Lizenn Delisle, Bruno Petton, Charlotte Corporeau, Fabrice Pernet
The Pacific oyster, Crassostrea gigas , is an osmoconforming bivalve exposed to wide salinity fluctuations. The physiological mechanisms used by oysters to cope with salinity stress are energy demanding and may impair other processes, such as defense against pathogens. This oyster species has been experiencing recurrent mortality events caused by the Ostreid herpesvirus 1 (OsHV-1). The objectives of this study were to investigate the effect of salinity (10, 15, 25 and 35‰) on energetic reserves, key enzyme activities and membrane fatty acids, and to identify the metabolic risk factors related to OsHV-1-induced mortality of oysters...
February 20, 2018: Biology Open
Zhimin Lu, Tony Hunter
Protein kinases regulate every aspect of cellular activity, whereas metabolic enzymes are responsible for energy production and catabolic and anabolic processes. Emerging evidence demonstrates that some metabolic enzymes, such as pyruvate kinase M2 (PKM2), phosphoglycerate kinase 1 (PGK1), ketohexokinase (KHK) isoform A (KHK-A), hexokinase (HK), and nucleoside diphosphate kinase 1 and 2 (NME1/2), that phosphorylate soluble metabolites can also function as protein kinases and phosphorylate a variety of protein substrates to regulate the Warburg effect, gene expression, cell cycle progression and proliferation, apoptosis, autophagy, exosome secretion, T cell activation, iron transport, ion channel opening, and many other fundamental cellular functions...
February 17, 2018: Trends in Biochemical Sciences
Jae-Il Roh, Yujin Kim, Jahyun Oh, Yunmi Kim, Jeehyun Lee, Jaehoon Lee, Kyung-Hee Chun, Han-Woong Lee
Autophagy is systematically regulated by upstream factors and nutrients. Recent studies reported that telomerase and hexokinase 2 [HK2) regulate autophagy through mTOR and that telomerase has the capacity to bind to the HK2 promoter. However, the molecular linkage among telomerase, HK2, and autophagy is not fully understood. Here, we show that HK2 connects telomerase to autophagy. HK2 inhibition in HepG2 cells suppressed TERT-induced autophagy activation and further enhancement by glucose deprivation. The HK2 downstream factor mTOR was responsible for the TERT-induced autophagy activation under glucose deprivation, implying that TERT promotes autophagy through an HK2-mTOR pathway...
2018: PloS One
Xi Zhao, Henri Palacci, Vinita Yadav, Michelle M Spiering, Michael K Gilson, Peter J Butler, Henry Hess, Stephen J Benkovic, Ayusman Sen
Enzymatic catalysis is essential to cell survival. In many instances, enzymes that participate in reaction cascades have been shown to assemble into metabolons in response to the presence of the substrate for the first enzyme. However, what triggers metabolon formation has remained an open question. Through a combination of theory and experiments, we show that enzymes in a cascade can assemble via chemotaxis. We apply microfluidic and fluorescent spectroscopy techniques to study the coordinated movement of the first four enzymes of the glycolysis cascade: hexokinase, phosphoglucose isomerase, phosphofructokinase and aldolase...
March 2018: Nature Chemistry
Xinli Mao, Hongyuan Zhu, Dinghai Luo, Liping Ye, Huifei Yin, Jinshun Zhang, Yan Zhang, Yu Zhang
Capsaicin is a principal component of hot red peppers and chili peppers. Previous studies have reported that capsaicin exhibits antitumor functions in a variety of tumor models. Although various mechanisms underlying the capsaicin‑mediated inhibition of tumor growth have been demonstrated, the impact of capsaicin on tumor metabolism has rarely been reported. The present study demonstrated that capsaicin exhibited an inhibitory effect on tumor glycolysis in esophageal squamous cell carcinoma (ESCC) cells. Following treatment with capsaicin, glucose consumption and lactate production in ESCC cells was decreased...
February 8, 2018: Molecular Medicine Reports
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