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https://www.readbyqxmd.com/read/28922425/hypoxia-inducible-factor-1-alpha-as-a-therapeutic-target-for-primary-effusion-lymphoma
#1
Prabha Shrestha, David A Davis, Ravindra P Veeranna, Robert F Carey, Coralie Viollet, Robert Yarchoan
Primary effusion lymphoma (PEL) is an aggressive B-cell lymphoma with poor prognosis caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Previous studies have revealed that HIF-1α, which mediates much of the cellular response to hypoxia, plays an important role in life cycle of KSHV. KSHV infection promotes HIF-1α activity, and several KSHV genes are in turn activated by HIF-1α. In this study, we investigated the effects of knocking down HIF-1α in PELs. We observed that HIF-1α knockdown in each of two PEL lines leads to a reduction in both aerobic and anaerobic glycolysis as well as lipid biogenesis, indicating that HIF-1α is necessary for maintaining a metabolic state optimal for growth of PEL...
September 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28922415/rewiring-monocyte-glucose-metabolism-via-c-type-lectin-signaling-protects-against-disseminated-candidiasis
#2
Jorge Domínguez-Andrés, Rob J W Arts, Rob Ter Horst, Mark S Gresnigt, Sanne P Smeekens, Jacqueline M Ratter, Ekta Lachmandas, Lily Boutens, Frank L van de Veerdonk, Leo A B Joosten, Richard A Notebaart, Carlos Ardavín, Mihai G Netea
Monocytes are innate immune cells that play a pivotal role in antifungal immunity, but little is known regarding the cellular metabolic events that regulate their function during infection. Using complementary transcriptomic and immunological studies in human primary monocytes, we show that activation of monocytes by Candida albicans yeast and hyphae was accompanied by metabolic rewiring induced through C-type lectin-signaling pathways. We describe that the innate immune responses against Candida yeast are energy-demanding processes that lead to the mobilization of intracellular metabolite pools and require induction of glucose metabolism, oxidative phosphorylation and glutaminolysis, while responses to hyphae primarily rely on glycolysis...
September 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28922372/reduction-of-organelle-motility-by-removal-of-potassium-and-other-solutes
#3
John W Murray, David Yin, Allan W Wolkoff
There are surprisingly few studies that describe how the composition of cell culture medium may affect the trafficking of organelles. Here we utilize time lapse multi-channel fluorescent imaging to show that short term exposure of Huh-7 cells to medium lacking potassium, sodium, or chloride strongly reduces but does not eliminate the characteristic back and forth and cell-traversing movement of fluorescent EGF (FL-EGF) containing organelles. We focused on potassium because of its relatively low abundance in media and serum and its energy requiring accumulation into cells...
2017: PloS One
https://www.readbyqxmd.com/read/28922027/further-evidence-of-how-unbuffered-starvation-at-4%C3%A2-c-influences-listeria-monocytogenes-egd-e-hcc23-f2365-and-scott-a
#4
Nathan A Jarvis, Corliss A O'Bryan, Elizabeth M Martin, Steven C Ricke, Michael G Johnson, Philip G Crandall
The soilborne pathogen Listeria monocytogenes frequently contaminates food products and food processing environments and is able to survive desiccation, high osmotic pressures, and starvation. However, little is known about how this pathogen survives starvation at 4°C. This study provides evidence that L. monocytogenes is able to survive total nutrient starvation for 4 weeks. L. monocytogenes strains EGD-e, Scott A, F2365, and HCC23 were starved individually in sterile water. Colony counts declined over 4 weeks, with Scott A declining the most rapidly...
September 18, 2017: Journal of Food Protection
https://www.readbyqxmd.com/read/28920951/srebp-controlled-glucose-metabolism-is-essential-for-nk-cell-functional-responses
#5
Nadine Assmann, Katie L O'Brien, Raymond P Donnelly, Lydia Dyck, Vanessa Zaiatz-Bittencourt, Róisín M Loftus, Paul Heinrich, Peter J Oefner, Lydia Lynch, Clair M Gardiner, Katja Dettmer, David K Finlay
Activated natural killer (NK) cells engage in a robust metabolic response that is required for normal effector function. Using genetic, pharmacological and metabolic analyses, we demonstrated an essential role for Srebp transcription factors in cytokine-induced metabolic reprogramming of NK cells that was independent of their conventional role in the control of lipid synthesis. Srebp was required for elevated glycolysis and oxidative phosphorylation and promoted a distinct metabolic pathway configuration in which glucose was metabolized to cytosolic citrate via the citrate-malate shuttle...
September 18, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28920148/differential-gene-expression-profiles-and-alternative-isoform-regulations-in-gill-of-nile-tilapia-in-response-to-acute-hypoxia
#6
Hong Lian Li, Hao Ran Lin, Jun Hong Xia
Fish often encounters exposures to acute environmental hypoxia either spatially or temporally. Gill organ plays important roles in response to hypoxic stress in fish. Few studies focus on the molecular regulation mechanisms of gills under hypoxic stress. In this study, we investigated the transcriptomic response to 12-h acute hypoxia in gill of a hypoxia tolerant fish, Nile tilapia Oreochromis niloticus through RNA sequencing (RNA-Seq). We sequenced messenger RNA from three control samples and three hypoxia-treated samples...
September 18, 2017: Marine Biotechnology
https://www.readbyqxmd.com/read/28918740/methylglyoxal-and-small-heat-shock-proteins
#7
REVIEW
M V Sudnitsyna, N B Gusev
Methylglyoxal is a highly reactive dicarbonyl compound formed during glucose metabolism and able to modify phospholipids, nucleic acids, and proteins belonging to the so-called dicarbonyl proteome. Small heat shock proteins participating in protection of the cell against different unfavorable conditions can be modified by methylglyoxal. The probability of methylglyoxal modification is increased in the case of distortion of glucose metabolism (diabetes), in the case of utilization of glycolysis as the main source of energy (malignancy), and/or at low rate of modified protein turnover...
July 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28917447/cell-penetrating-peptides-to-dissect-host-pathogen-protein-protein-interactions-in-theileria-transformed-leukocytes
#8
REVIEW
Malak Haidar, Perle Latré de Laté, Eileen J Kennedy, Gordon Langsley
One powerful application of cell penetrating peptides is the delivery into cells of molecules that function as specific competitors or inhibitors of protein-protein interactions. Ablating defined protein-protein interactions is a refined way to explore their contribution to a particular cellular phenotype in a given disease context. Cell-penetrating peptides can be synthetically constrained through various chemical modifications that stabilize a given structural fold with the potential to improve competitive binding to specific targets...
September 7, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28916775/measuring-glucose-cerebral-metabolism-in-the-healthy-mouse-using-hyperpolarized-13-c-magnetic-resonance
#9
Mor Mishkovsky, Brian Anderson, Magnus Karlsson, Mathilde H Lerche, A Dean Sherry, Rolf Gruetter, Zoltan Kovacs, Arnaud Comment
The mammalian brain relies primarily on glucose as a fuel to meet its high metabolic demand. Among the various techniques used to study cerebral metabolism, (13)C magnetic resonance spectroscopy (MRS) allows following the fate of (13)C-enriched substrates through metabolic pathways. We herein demonstrate that it is possible to measure cerebral glucose metabolism in vivo with sub-second time resolution using hyperpolarized (13)C MRS. In particular, the dynamic (13)C-labeling of pyruvate and lactate formed from (13)C-glucose was observed in real time...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916747/hormetic-potential-of-methylglyoxal-a-side-product-of-glycolysis-in-switching-tumours-from-growth-to-death
#10
Marie-Julie Nokin, Florence Durieux, Justine Bellier, Olivier Peulen, Koji Uchida, David A Spiegel, James R Cochrane, Craig A Hutton, Vincent Castronovo, Akeila Bellahcène
Metabolic reprogramming toward aerobic glycolysis unavoidably favours methylglyoxal (MG) and advanced glycation end products (AGEs) formation in cancer cells. MG was initially considered a highly cytotoxic molecule with potential anti-cancer value. However, we have recently demonstrated that MG enhanced tumour growth and metastasis. In an attempt to understand this dual role, we explored MG-mediated dicarbonyl stress status in four breast and glioblastoma cancer cell lines in relation with their glycolytic phenotype and MG detoxifying capacity...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916726/the-nqo1-bioactivatable-drug-%C3%AE-lapachone-alters-the-redox-state-of-nqo1-pancreatic-cancer-cells-causing-perturbation-in-central-carbon-metabolism
#11
Molly A Silvers, Stanislaw Deja, Naveen Singh, Robert A Egnatchik, Jessica Sudderth, Xiuquan Luo, Muhammad S Beg, Shawn C Burgess, Ralph J DeBerardinis, David A Boothman, Matthew E Merritt
Many cancer treatments, such as those for managing recalcitrant tumors like pancreatic ductal adenocarcinoma, cause off-target toxicities in normal, healthy tissue, highlighting the need for more tumor-selective chemotherapies. β-Lapachone is bioactivated by NAD(P)H:quinone oxidoreductase 1 (NQO1). This enzyme exhibits elevated expression in most solid cancers and therefore is a potential cancer-specific target. β-Lapachone's therapeutic efficacy partially stems from the drug's induction of a futile NQO1-mediated redox cycle that causes high levels of superoxide, then peroxide formation, which damages DNA and causes hyperactivation of poly (ADP-ribose) polymerase (PARP), resulting in extensive NAD+/ATP depletion...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28916706/the-expression-of-ldh-c-in-the-skeletal-muscle-of-plateau-pika-ochotona-curzoniae-enhances-adaptation-to-a-hypoxic-environment
#12
Zhi F An, Deng B Wei, Lian Wei, Yang Wang, Lin N Wei
The plateau pika (Ochotona curzoniae) is a species of sprint-running alpine animals in the Qinghai-Tibet Plateau, which is a harsh highland hypoxic environment. Ldh-c is expressed in the testis, sperm and somatic tissues of plateau pika. To reveal the role and physiological mechanisms of sperm-specific lactate dehydrogenase (LDH-C4), in plateau pika to adapt to hypoxic environment, an adenoviral line of pMultiRNAi-Ldhc was constructed and injected into the bilateral biceps femoris of the hind legs. The swimming times of the pikas, and the Ldh-c expression levels, total LDH activities and ATP levels in skeletal muscle, were measured after the pikas were raised in the trapped site for 5 days...
September 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28916476/pharmacologic-ascorbate-induces-neuroblastoma-cell-death-by-hydrogen-peroxide-mediated-dna-damage-and-reduction-in-cancer-cell-glycolysis
#13
Enlong Ma, Ping Chen, Heather M Wilkins, Tao Wang, Russell H Swerdlow, Qi Chen
An ascorbate-mediated production of oxidative stress has been shown to retard tumor growth. Subsequent glycolysis inhibition has been suggested. Here, we further define the mechanisms relevant to this observation. Ascorbate was cytotoxic to human neuroblastoma cells through the production of H2O2, which led to ATP depletion, inhibited GAPDH, and non-apoptotic and non-autophagic cell death. The mechanism of cytotoxicity is different when PARP-dependent DNA repair machinery is active or inhibited. Ascorbate-generated H2O2 damaged DNA, activated PARP, depleted NAD+, and reduced glycolysis flux...
September 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28915790/the-process-related-dynamics-of-microbial-community-during-a-simulated-fermentation-of-chinese-strong-flavored-liquor
#14
Yanyan Zhang, Xiaoyu Zhu, Xiangzhen Li, Yong Tao, Jia Jia, Xiaohong He
BACKGROUND: Famous Chinese strong-flavored liquor (CSFL) is brewed by microbial consortia in a special fermentation pit (FT). However, the fermentation process was not fully understood owing to the complicate community structure and metabolism. In this study, the process-related dynamics of microbial communities and main flavor compounds during the 70-day fermentation process were investigated in a simulated fermentation system. RESULTS: A three-phase model was proposed to characterize the process of the CSFL fermentation...
September 15, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28915575/hexokinase-2-promotes-tumor-growth-and-metastasis-by-regulating-lactate-production-in-pancreatic-cancer
#15
Marybeth Anderson, Raoud Marayati, Richard Moffitt, Jen Jen Yeh
Pancreatic ductal adenocarcinoma (PDAC) is a KRAS-driven cancer with a high incidence of metastasis and an overall poor prognosis. Previous work in a genetically engineered mouse model of PDAC showed glucose metabolism to be important for maintaining tumor growth. Multiple glycolytic enzymes, including hexokinase 2 (HK2), were upregulated in primary PDAC patient tumors, supporting a role for glycolysis in promoting human disease. HK2 was most highly expressed in PDAC metastases, suggesting a link between HK2 and aggressive tumor biology...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915394/overcoming-the-warburg-effect-is-it-the-key-to-survival-in-sepsis
#16
REVIEW
David Bar-Or, Matthew Carrick, Allen Tanner, Mark J Lieser, Leonard T Rael, Edward Brody
Sepsis is a leading cause of mortality in the U.S. and Europe. Sepsis and septic shock are the results of severe metabolic abnormalities following infection. Aerobic glycolysis (the Warburg Effect) is as much a hallmark of sepsis as it is of cancer. Warburg observed that cancer cells generated energy through glycolysis (generation of ATP through degradation of glucose, usually associated with anaerobic conditions) rather than through oxidative phosphorylation (generation of ATP through the mitochondrial inner membrane via the tricarboxylic acid cycle, usually associated with aerobic conditions)...
September 8, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/28915065/targeting-hif-1%C3%AE-pdk1-axis-by-dichloroacetate-dca-suppresses-bleomycin-induced-pulmonary-fibrosis
#17
Justin Goodwin, Hyunsung Choi, Meng-Hsiung Hsieh, Michael L Neugent, Jung-Mo Ahn, Heather N Hayenga, Pankaj K Singh, David B Shackelford, In-Kyu Lee, Vladimir Shulaev, Shanta Dhar, Norihiko Takeda, Jung-Whan Kim
RATIONALE: Hypoxia has long been implicated in the pathogenesis of fibrotic diseases. Aberrantly activated myofibroblasts are the primary pathological driver of fibrotic progression, yet how various microenvironmental influences such as hypoxia contribute to their sustained activation and differentiation is poorly understood. OBJECTIVES: As a defining feature of hypoxia is its impact on cellular metabolism, we sought to investigate how hypoxia-induced metabolic reprogramming affects myofibroblast differentiation and fibrotic progression, and to test the pre-clinical efficacy of targeting glycolytic metabolism for the treatment of pulmonary fibrosis...
September 15, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28914242/assessment-of-plaque-regrowth-with-a-probiotic-toothpaste-containing-lactobacillus-paracasei-a-spectrophotometric-study
#18
Shruti Srinivasan, Bhojraj Nandlal, M Vsst Subba Rao
BACKGROUND: Probiotics are live microorganisms which when administered in adequate amounts confer health benefits on the host. Commonly, most of the organisms ascribed as having probiotic properties belong to the genera Lactobacillus and Bifidobacterium and milk is the most commonly used vehicle. OBJECTIVES: The study was aimed at analyzing the biofilm formation by plaque regrowth method upon the usage of a probiotic toothpaste containing Lactobacillus paracasei by measuring the optical density using a spectrophotometer...
October 2017: Journal of the Indian Society of Pedodontics and Preventive Dentistry
https://www.readbyqxmd.com/read/28913935/induction-of-cancer-cell-stemness-by-depletion-of-macrohistone-h2a1-in-hepatocellular-carcinoma
#19
Oriana Lo Re, Caterina Fusilli, Francesca Rappa, Matthias Van Haele, Julien Douet, Jana Pindjakova, Sura Wanessa Rocha, Illar Pata, Barbora Valčíková, Stjepan Uldrijan, Raymond S Yeung, Christina Alves Peixoto, Tania Roskams, Marcus Buschbeck, Tommaso Mazza, Manlio Vinciguerra
Hepatocellular carcinomas (HCC) contain a sub-population of cancer stem cells (CSCs), which exhibit stem-cell like features and are responsible for tumor relapse, metastasis, and chemoresistance. The development of effective treatments for HCC will depend on a molecular-level understanding of the specific pathways driving CSC emergence and stemness. MacroH2A1 is a variant of the histone H2A and an epigenetic regulator of stem cell function, where it promotes differentiation and, conversely, acts as a barrier to somatic cell reprogramming...
September 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28913617/fingolimod-induces-neuronal-specific-gene-expression-with-potential-neuroprotective-outcomes-in-maturing-neuronal-progenitor-cells-exposed-to-hiv
#20
Rebeca Geffin, Ricardo Martinez, Alicia de Las Pozas, Biju Issac, Micheline McCarthy
Fingolimod (FTY720), a structural analogue of sphingosine, targets sphingosine-1-phosphate receptor signaling and is currently an immunomodulatory therapy for multiple sclerosis. Fingolimod accesses the central nervous system (CNS) where its active metabolite, fingolimod phosphate (FTY720-P), has pleotropic neuroprotective effects in an inflammatory microenvironment. To investigate potential neuronal-specific mechanisms of fingolimod neuroprotection, we cultured the human neuronal progenitor cell line, hNP1, in differentiation medium supplemented with HIV- or Mock-infected supernatants, with or without FTY720-P...
September 14, 2017: Journal of Neurovirology
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