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https://www.readbyqxmd.com/read/28930961/impact-of-a-novel-phosphoinositol-3-kinase-inhibitor-in-preventing-mitochondrial-dna-damage-and-damage-associated-molecular-pattern-accumulation-results-from-the-biochronicity-project
#1
George Edward Black, Kyle K Sokol, Donald M Moe, Jon D Simmons, David Muscat, Victor Pastukh, Gina Capley, Olena Gorodnya, Mykhaylo Ruchko, Mark B Roth, Mark Gillespie, Matthew J Martin
BACKGROUND: Despite improvements in the management of severely injured patients, development of multiple organ dysfunction syndrome (MODS) remains a morbid complication of traumatic shock. One of the key attributes of MODS is a profound bioenergetics crisis, for which the mediators and mechanisms are poorly understood. We hypothesized that metabolic uncoupling using an experimental phosphoinositol-3 kinase (PI3-K) inhibitor, LY294002 (LY), may prevent mitochondrial abnormalities that lead to the generation of mitochondrial DNA (mtDNA) damage and the release of mtDNA damage-associated molecular patterns (DAMPs)...
October 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28927964/behavioral-responses-of-beluga-whales-delphinapterus-leucas-to-environmental-variation-in-an-arctic-estuary
#2
Paul A Anderson, Russell B Poe, Laura A Thompson, Nansen Weber, Tracy A Romano
Some Arctic estuaries serve as substrate rubbing sites for beluga whales (Delphinapterus leucas) in the summer, representing a specialized resource for the species. Understanding how environmental variation affects the species' behavior is essential to management of these habitats in coming years as the climate changes. Spatiotemporal and environmental variables were recorded for behavioral observations, during which focal groups of whales in an estuary were video-recorded for enumeration and behavioral analysis...
September 16, 2017: Behavioural Processes
https://www.readbyqxmd.com/read/28925557/analysis-of-multiple-haloarchaeal-genomes-suggests-that-the-quinone-dependent-respiratory-nitric-oxide-reductase-is-an-important-source-of-nitrous-oxide-in-hypersaline-environments
#3
Javier Torregrosa-Crespo, Pedro González-Torres, Vanesa Bautista, Julia M Esclapez, Carmen Pire, Mónica Camacho, María José Bonete, David J Richardson, Nicholas J Watmough, Rosa María Martínez-Espinosa
Microorganisms, including Bacteria and Archaea, play a key role in denitrification, which is the major mechanism by which fixed nitrogen returns to the atmosphere from soil and water. Whilst the enzymology of denitrification is well understood in Bacteria, the details of the last two reactions in this pathway, which catalyse the reduction of nitric oxide (NO) via nitrous oxide (N2 O) to nitrogen (N2 ), are little studied in Archaea, and hardly at all in haloarchaea. This work describes an extensive interspecies analysis of both complete and draft haloarchaeal genomes aimed at identifying the genes that encode respiratory nitric oxide reductases (Nors)...
September 19, 2017: Environmental Microbiology Reports
https://www.readbyqxmd.com/read/28925102/continued-alcohol-misuse-in-human-cirrhosis-is-associated-with-an-impaired-gut-liver-axis
#4
Jasmohan S Bajaj, Genta Kakiyama, Derrick Zhao, Hajime Takei, Andrew Fagan, Phillip Hylemon, Huiping Zhou, William M Pandak, Hiroshi Nittono, Oliver Fiehn, Nita Salzman, Mary Holtz, Pippa Simpson, Edith A Gavis, Douglas M Heuman, Runping Liu, Dae Joong Kang, Masoumeh Sikaroodi, Patrick M Gillevet
BACKGROUND: Cirrhosis and alcohol can independently affect the gut-liver axis with systemic inflammation. However their concurrent impact in humans is unclear. AIM: Determine the effect of continued alcohol misuse on the gut-liver axis in cirrhotic patients. METHODS: Age and MELD-balanced cirrhotic patients who were currently drinking (Alc) or abstinent (NAlc), and healthy controls underwent serum and stool collection. A subset underwent upper endoscopy and colonoscopy for biopsies and duodenal fluid collection...
September 19, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28923861/mct1-inhibitor-azd3965-increases-mitochondrial-metabolism-facilitating-combination-therapy-and-non-invasive-magnetic-resonance-spectroscopy
#5
Mounia Beloueche-Babari, Slawomir Wantuch, Teresa Casals Galobart, Markela Koniordou, Harold G Parkes, Vaitha Arunan, Yuen-Li Chung, Thomas R Eykyn, Paul D Smith, Martin O Leach
Monocarboxylate transporters (MCT) modulate tumor cell metabolism and offer promising therapeutic targets for cancer treatment. Understanding the impact of MCT blockade on tumor cell metabolism may help develop combination strategies or identify pharmacodynamic biomarkers to support the clinical development of MCT inhibitors now in clinical trials. In this study, we assessed the impact of the MCT1 inhibitor AZD3965 on cancer cell metabolism in vitro and in vivo. Exposing human lymphoma and colon carcinoma cells to AZD3965 increased MCT4-dependent accumulation of intracellular lactate, inhibiting monocarboxylate influx and efflux...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28923859/upregulation-of-cystathionine-%C3%AE-synthase-in-colonic-epithelia-reprograms-metabolism-and-promotes-carcinogenesis
#6
Ches'Nique M Phillips, John Zatarain, Michael E Nicholls, Craig Porter, Steve G Widen, Ketan Thanki, Paul Johnson, Muhammad U Jawad, Mary Pat Moyer, James W Randall, Judith L Hellmich, Manjit Maskey, Suimin Qiu, Thomas Wood, Nadiya Druzhyna, Bartosz Szczesny, Katalin Modis, Csaba Szabo, Celia Chao, Mark R Hellmich
The transsulfuration enzyme cystathionine-β-synthase (CBS) and its product hydrogen sulfide (H2S) are aberrantly upregulated in colorectal cancers, where they contribute to tumor growth and progression by both autocrine and paracrine mechanisms. However, it is unknown whether the CBS/H2S axis plays a role in colorectal carcinogenesis. Here, we report upregulation of CBS in human biopsies of precancerous adenomatous polyps and show that forced upregulation of CBS in an adenoma-like colonic epithelial cell line is sufficient to induce metabolic and gene expression profiles characteristic of colorectal cancer cells...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28923556/de-novo-assembly-and-transcriptome-characterization-of-the-freshwater-prawn-palaemonetes-argentinus-implications-for-a-detoxification-response
#7
C Fernando García, Nicolas Pedrini, Arturo Sánchez-Paz, Carlos S Reyna-Blanco, Sabrina Lavarias, Adriana Muhlia-Almazán, Analía Fernández-Giménez, Aldana Laino, Enrique de-la-Re-Vega, German Lukaszewicz, Alonso A López-Zavala, Luis G Brieba, Michael F Criscitello, Jesús S Carrasco-Miranda, Karina D García-Orozco, Adrian Ochoa-Leyva, Enrique Rudiño-Piñera, Alejandro Sanchez-Flores, Rogerio R Sotelo-Mundo
Palaemonetes argentinus, an abundant freshwater prawn species in the northern and central region of Argentina, has been used as a bioindicator of environmental pollutants as it displays a very high sensitivity to pollutants exposure. Despite their extraordinary ecological relevance, a lack of genomic information has hindered a more thorough understanding of the molecular mechanisms potentially involved in detoxification processes of this species. Thus, transcriptomic profiling studies represent a promising approach to overcome the limitations imposed by the lack of extensive genomic resources for P...
September 8, 2017: Marine Genomics
https://www.readbyqxmd.com/read/28920697/n%C3%AE%C2%B5-and-o-acetylation-in-mycobacterium-tuberculosis-lineage-7-and-lineage-4-strains-proteins-involved-in-bioenergetics-virulence-and-antimicrobial-resistance-are-acetylated
#8
Alemayehu Godana Birhanu, Solomon Abebe Yimer, Carol Holm-Hansen, Gunnstein Norheim, Abraham Aseffa, Markos Abebe, Tone Tønjum
Increasing evidence demonstrates that lysine acetylation is involved in Mycobacterium tuberculosis (Mtb) virulence and pathogenesis. However, previous investigations in Mtb have only monitored acetylation at lysine residues using selected reference strains. We analyzed the global Nε- and O-acetylation of 3 Mtb isolates; 2 lineage 7 clinical isolates and the lineage 4 H37Rv reference strain. Quantitative acetylome analysis resulted in identification of 2490 class-I acetylation sites, among them 2349 O-acetylation and 141 Nε-acetylation sites, derived from 953 unique proteins...
September 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28919076/mitochondrial-priming-by-cd28
#9
Ramon I Klein Geltink, David O'Sullivan, Mauro Corrado, Anna Bremser, Michael D Buck, Joerg M Buescher, Elke Firat, Xuekai Zhu, Gabriele Niedermann, George Caputa, Beth Kelly, Ursula Warthorst, Anne Rensing-Ehl, Ryan L Kyle, Lana Vandersarren, Jonathan D Curtis, Annette E Patterson, Simon Lawless, Katarzyna Grzes, Jing Qiu, David E Sanin, Oliver Kretz, Tobias B Huber, Sophie Janssens, Bart N Lambrecht, Angelika S Rambold, Edward J Pearce, Erika L Pearce
T cell receptor (TCR) signaling without CD28 can elicit primary effector T cells, but memory T cells generated during this process are anergic, failing to respond to secondary antigen exposure. We show that, upon T cell activation, CD28 transiently promotes expression of carnitine palmitoyltransferase 1a (Cpt1a), an enzyme that facilitates mitochondrial fatty acid oxidation (FAO), before the first cell division, coinciding with mitochondrial elongation and enhanced spare respiratory capacity (SRC). microRNA-33 (miR33), a target of thioredoxin-interacting protein (TXNIP), attenuates Cpt1a expression in the absence of CD28, resulting in cells that thereafter are metabolically compromised during reactivation or periods of increased bioenergetic demand...
September 1, 2017: Cell
https://www.readbyqxmd.com/read/28918113/regulation-of-mitochondrial-bioenergetics-by-the-non-canonical-roles-of-mitochondrial-dynamics-proteins-in-the-heart
#10
REVIEW
Wang Wang, Celia Fernandez-Sanz, Shey-Shing Sheu
Recent advancement in mitochondrial research has significantly extended our knowledge on the role and regulation of mitochondria in health and disease. One important breakthrough is the delineation of how mitochondrial morphological changes, termed mitochondrial dynamics, are coupled to the bioenergetics and signaling functions of mitochondria. In general, it is believed that fusion leads to an increased mitochondrial respiration efficiency and resistance to stress-induced dysfunction while fission does the contrary...
September 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28912578/tumour-acidosis-from-the-passenger-to-the-driver-s-seat
#11
REVIEW
Cyril Corbet, Olivier Feron
The high metabolic demand of cancer cells leads to an accumulation of H(+) ions in the tumour microenvironment. The disorganized tumour vasculature prevents an efficient wash-out of H(+) ions released into the extracellular medium but also favours the development of tumour hypoxic regions associated with a shift towards glycolytic metabolism. Under hypoxia, the final balance of glycolysis, including breakdown of generated ATP, is the production of lactate and a stoichiometric amount of H(+) ions. Another major source of H(+) ions results from hydration of CO2 produced in the more oxidative tumour areas...
September 15, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28904018/dyslipidemia-impairs-mitochondrial-trafficking-and-function-in-sensory-neurons
#12
Amy E Rumora, Stephen I Lentz, Lucy M Hinder, Samuel W Jackson, Andrew Valesano, Gideon E Levinson, Eva L Feldman
Mitochondrial trafficking plays a central role in dorsal root ganglion (DRG) neuronal cell survival and neurotransmission by transporting mitochondria from the neuronal cell body throughout the bundles of DRG axons. In type 2 diabetes (T2DM), dyslipidemia and hyperglycemia damage DRG neurons and induce mitochondrial dysfunction; however, the impact of free fatty acids and glucose on mitochondrial trafficking in DRG neurons remains unknown. To evaluate the impact of free fatty acids compared to hyperglycemia on mitochondrial transport, primary adult mouse DRG neuron cultures were treated with physiologic concentrations of palmitate and glucose and assessed for alterations in mitochondrial trafficking, mitochondrial membrane potential, and mitochondrial bioenergetics...
September 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28901530/metabolic-orchestration-of-t-lineage-differentiation-and-function
#13
REVIEW
Carmen S Yong, Daouda Mousatpha Abba Moussa, Gaspard Cretenet, Sandrina Kinet, Valérie Dardalhon, Naomi Taylor
T cells are stimulated by the engagement of antigen, cytokine, pathogen and hormone receptors. While research performed over many years has focused on deciphering the molecular components of these pathways, recent data underscore the importance of the metabolic environment in conditioning responses to receptor engagement. The ability of T cells to undergo a massive proliferation and cytokine secretion in response to receptor signals requires alterations to their bioenergetic homeostasis, allowing them to meet new energetic and biosynthetic demands...
September 13, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28901527/hypoxia-promotes-migration-invasion-and-glycolysis-in-head-and-neck-squamous-cell-carcinoma-via-an-hif-1%C3%AE-mtdh-loop
#14
Gangcai Zhu, Fusen Peng, Wei Gong, Li She, Ming Wei, Haolei Tan, Changhan Chen, Diekuo Zhang, Guo Li, Donghai Huang, Xin Zhang, Yong Liu
Hypoxia is a hallmark of progressive cancer. Hypoxic cancer cells trigger glycolysis in response to a decreased O2 supply to meet metabolic and bioenergetic demands. Meanwhile, these responses to hypoxia and alterations of the microenvironment promote cancer cell metastasis by increasing transcription of hypoxia-inducible factor (HIF)-regulated genes. However, the detailed mechanism by which hypoxia regulates cancer cell metastasis and glycolysis remains to be investigated. In the present study, we identified that metadherin (MTDH), a multifaceted oncogene, is involved in the regulation of head and neck squamous cell carcinoma (HNSCC) metastasis and invasion under hypoxic conditions...
September 7, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28899812/the-starving-brain-overfed-meets-undernourished-in-the-pathology-of-mild-cognitive-impairment-mci-and-alzheimer-s-disease-ad
#15
REVIEW
Kelly J Gibas
Type II Diabetes affects 400 million people worldwide (IDF, 2013). The pathology is paradoxical: internal starvation activated by overfeeding. Hyperinsulinemic impairments of glucose homeostasis are treated with anti-hyperglycemics exacerbating cell starvation, inducing hypoglycemia and raising respiratory quotient. Reductions in hyperglycemia are achieved at the expense of glucose dependency and metabolic inflexibility (Gibas & Gibas, 2017). The brain is not immune from these cycles of starvation. The bioenergetic model characterizes propagation of late-onset, sporadic Alzheimer's disease as loss of molecular fidelity and compromised energy originating in brain networks with highest metabolic demand...
September 9, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28899755/nad-in-aging-molecular-mechanisms-and-translational-implications
#16
REVIEW
Evandro F Fang, Sofie Lautrup, Yujun Hou, Tyler G Demarest, Deborah L Croteau, Mark P Mattson, Vilhelm A Bohr
The coenzyme NAD(+) is critical in cellular bioenergetics and adaptive stress responses. Its depletion has emerged as a fundamental feature of aging that may predispose to a wide range of chronic diseases. Maintenance of NAD(+) levels is important for cells with high energy demands and for proficient neuronal function. NAD(+) depletion is detected in major neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, cardiovascular disease and muscle atrophy. Emerging evidence suggests that NAD(+) decrements occur in various tissues during aging, and that physiological and pharmacological interventions bolstering cellular NAD(+) levels might retard aspects of aging and forestall some age-related diseases...
September 9, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28895059/central-nervous-system-penetrating-antiretrovirals-impair-energetic-reserve-in-striatal-nerve-terminals
#17
Kelly L Stauch, Katy Emanuel, Benjamin G Lamberty, Brenda Morsey, Howard S Fox
The use of antiretroviral (ARV) drugs with central nervous system (CNS) penetration effectiveness (CPE) may be useful in the treatment of HIV-associated neurocognitive disorder (HAND) as well as targeting a CNS reservoir in strategies to achieve a functional cure for HIV. However, increased cognitive deficits are linked to at least one of these drugs (efavirenz). As mitochondrial dysfunction has been found with a number of ARVs, and as such can affect neuronal function, the objective of this study was to assess the effects of ARV with high CPE for toxicological profiles on presynaptic nerve terminal energy metabolism...
September 11, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28891816/syntaphilin-controls-a-mitochondrial-rheostat-for-proliferation-motility-decisions-in-cancer
#18
M Cecilia Caino, Jae Ho Seo, Yuan Wang, Dayana B Rivadeneira, Dmitry I Gabrilovich, Eui Tae Kim, Ashani T Weeraratna, Lucia R Languino, Dario C Altieri
Tumors adapt to an unfavorable microenvironment by controlling the balance between cell proliferation and cell motility, but the regulators of this process are largely unknown. Here, we show that an alternatively spliced isoform of syntaphilin (SNPH), a cytoskeletal regulator of mitochondrial movements in neurons, is directed to mitochondria of tumor cells. Mitochondrial SNPH buffers oxidative stress and maintains complex II-dependent bioenergetics, sustaining local tumor growth while restricting mitochondrial redistribution to the cortical cytoskeleton and tumor cell motility...
September 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28890369/selenium-incorporated-guar-gum-nanoparticles-safeguards-mitochondrial-bioenergetics-during-ischemia-reperfusion-injury-in-h9c2-cardiac-cells
#19
R S Soumya, Prathapan Ayyappan, P Salin Raj, V P Vineetha, K G Raghu
The application of nanotechnology has created high impact in diagnosis and prognosis of various disorders including cardiovascular diseases. In the present study, we investigated the beneficial effect of selenium incorporated guar gum nanoparticles (SGG) compared to nascent selenium (Se) and guar gum nanoparticle (GGN) against ischemia-reperfusion induced alterations in oxidative phosphorylation and energy metabolism in H9c2 cardiac cells. Ischemia and reperfusion were induced for 1h. The alterations in activities of various complexes (complex 1, II, III and IV) of mitochondrial electron transport chain (ETC), aconitase activity, oxygen consumption rate, and the ATP content were seen...
September 7, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28888963/sex-differences-in-the-mitochondrial-bioenergetics-of-astrocytes-but-not-microglia-at-a-physiologically-relevant-brain-oxygen-tension
#20
Sausan M Jaber, Evan A Bordt, Niraj M Bhatt, Daniel M Lewis, Sharon Gerecht, Gary Fiskum, Brian M Polster
Biological sex is thought to influence mitochondrial bioenergetic function. Previous respiration measurements examining brain mitochondrial sex differences were made at atmospheric oxygen using isolated brain mitochondria. Oxygen is 160 mm Hg (21%) in the atmosphere, while the oxygen tension in the brain generally ranges from ∼5 to 45 mm Hg (∼1-6% O2). This study tested the hypothesis that sex and/or brain physiological oxygen tension influence the mitochondrial bioenergetic properties of primary rat cortical astrocytes and microglia...
September 6, 2017: Neurochemistry International
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