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https://www.readbyqxmd.com/read/28736244/the-use-of-stable-isotopes-in-the-study-of-human-pathophysiology
#1
Evelina Charidemou, Tom Ashmore, Julian L Griffin
The growing prevalence of metabolic diseases including fatty liver disease and Type 2 diabetes has increased the emphasis on understanding metabolism at the mechanistic level and how it is perturbed in disease. Metabolomics is a continually expanding field that seeks to measure metabolites in biological systems during a physiological stimulus or a genetic alteration. Typically, metabolomics studies provide total pool sizes of metabolites rather than dynamic flux measurements. More recently there has been a resurgence in approaches that use stable isotopes (e...
July 20, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28735082/aeromonas-caviae-alters-the-cytosolic-and-mitochondrial-creatine-kinase-activities-in-experimentally-infected-silver-catfish-impairment-on-renal-bioenergetics
#2
Matheus D Baldissera, Carine F Souza, Guerino B Júnior, Camila Marina Verdi, Karen L S Moreira, Maria Izabel U M da Rocha, Marcelo L da Veiga, Roberto C V Santos, Bruno S Vizzotto, Bernardo Baldisserotto
Cytosolic and mitochondrial creatine kinases (CK), through the creatine kinase-phosphocreatine (CK/PCr) system, provide a temporal and spatial energy buffer to maintain cellular energy homeostasis. However, the effects of bacterial infections on the kidney remain poorly understood and are limited only to histopathological analyses. Thus, the aim of this study was to investigate the involvement of cytosolic and mitochondrial CK activities in renal energetic homeostasis in silver catfish experimentally infected with Aeromonas caviae...
July 19, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28733449/mitochondrial-function-in-engineered-cardiac-tissues-is-co-regulated-by-extracellular-matrix-elasticity-and-tissue-alignment
#3
Davi Marco Lyra-Leite, Allen Mariano Andres, Andrew Patrick Petersen, Nethika Ruvini Ariyasinghe, Nathan Cho, Jezell Athena Lee, Roberta A Gottlieb, Megan L McCain
Mitochondria in cardiac myocytes are critical for generating ATP to meet the high metabolic demands associated with sarcomere shortening. Distinct remodeling of mitochondrial structure and function occur in cardiac myocytes in both developmental and pathological settings. However, the factors that underlie these changes are poorly understood. Because remodeling of tissue architecture and extracellular matrix (ECM) elasticity are also hallmarks of ventricular development and disease, we hypothesize that these environmental factors regulate mitochondrial function in cardiac myocytes...
July 21, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28732077/mutations-in-the-caenorhabditis-elegans-orthologs-of-human-genes-required-for-mitochondrial-trna-modification-cause-similar-electron-transport-chain-defects-but-different-nuclear-responses
#4
Carmen Navarro-González, Ismaïl Moukadiri, Magda Villarroya, Ernesto López-Pascual, Simon Tuck, M-Eugenia Armengod
Several oxidative phosphorylation (OXPHOS) diseases are caused by defects in the post-transcriptional modification of mitochondrial tRNAs (mt-tRNAs). Mutations in MTO1 or GTPBP3 impair the modification of the wobble uridine at position 5 of the pyrimidine ring and cause heart failure. Mutations in TRMU affect modification at position 2 and cause liver disease. Presently, the molecular basis of the diseases and why mutations in the different genes lead to such different clinical symptoms is poorly understood...
July 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28730540/gigaspora-margarita-with-and-without-its-endobacterium-shows-adaptive-responses-to-oxidative-stress
#5
Francesco Venice, Maria Concetta de Pinto, Mara Novero, Stefano Ghignone, Alessandra Salvioli, Paola Bonfante
Arbuscular mycorrhizal (AM) fungi experience oxidative stress during the plant-fungal interaction, due to endogenous reactive oxygen species (ROS) produced by fungal metabolism and exogenous ROS produced by plant cells. Here, we examine the responses to H2O2 in Gigaspora margarita, an AM fungus containing the endobacterial symbiont Candidatus Glomeribacter gigasporarum (CaGg). Previous studies revealed that G. margarita with its endobacterium produces more ATP and has higher respiratory activity than a cured line that lacks the endobacterium...
July 20, 2017: Mycorrhiza
https://www.readbyqxmd.com/read/28730528/sulforaphane-promotes-mitochondrial-protection-in-sh-sy5y-cells-exposed-to-hydrogen-peroxide-by-an-nrf2-dependent-mechanism
#6
Marcos Roberto de Oliveira, Flávia de Bittencourt Brasil, Cristina Ribas Fürstenau
Sulforaphane (SFN; C6H11NOS2) is an isothiocyanate found in cruciferous vegetables, such as broccoli, kale, and radish. SFN exhibits antioxidant, anti-apoptotic, anti-tumor, and anti-inflammatory activities in different cell types. However, it was not previously demonstrated whether and how this natural compound would exert mitochondrial protection experimentally. Therefore, we investigated here the effects of a pretreatment (for 30 min) with SFN at 5 μM on mitochondria obtained from human neuroblastoma SH-SY5Y cells exposed to hydrogen peroxide (H2O2) at 300 μM for 24 h...
July 20, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28725193/annual-meeting-of-the-international-society-of-cancer-metabolism-iscam-metabolic-networks-in-cancer
#7
Nicola Baldini, Angelo De Milito, Olivier Feron, Robert J Gillies, Carine Michiels, Angela M Otto, Silvia Pastoreková, Stine F Pedersen, Paolo E Porporato, Pierre Sonveaux, Claudiu T Supuran, Sofia Avnet
Cancers are metabolic entities wherein cancer cells adapt their metabolism to their oncogenic agenda and microenvironmental influences. Metabolically different cancer cell subpopulations collaborate to optimize nutrient delivery with respect to immediate bioenergetic and biosynthetic needs. They can also metabolically exploit host cells. These metabolic networks are directly linked with cancer progression, treatment resistance and relapse. Conversely, metabolic alterations in cancer are exploited for anticancer therapy, imaging and personalized medicine...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28724806/nicotinamide-mononucleotide-requires-sirt3-to-improve-cardiac-function-and-bioenergetics-in-a-friedreich-s-ataxia-cardiomyopathy-model
#8
Angelical S Martin, Dennis M Abraham, Kathleen A Hershberger, Dhaval P Bhatt, Lan Mao, Huaxia Cui, Juan Liu, Xiaojing Liu, Michael J Muehlbauer, Paul A Grimsrud, Jason W Locasale, R Mark Payne, Matthew D Hirschey
Increasing NAD+ levels by supplementing with the precursor nicotinamide mononucleotide (NMN) improves cardiac function in multiple mouse models of disease. While NMN influences several aspects of mitochondrial metabolism, the molecular mechanisms by which increased NAD+ enhances cardiac function are poorly understood. A putative mechanism of NAD+ therapeutic action exists via activation of the mitochondrial NAD+-dependent protein deacetylase sirtuin 3 (SIRT3). We assessed the therapeutic efficacy of NMN and the role of SIRT3 in the Friedreich's ataxia cardiomyopathy mouse model (FXN-KO)...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28724704/physiological-responses-to-short-term-thermal-stress-in-mayfly-neocloeon-triangulifer-larvae-in-relation-to-upper-thermal-limits
#9
Kyoung Sun Kim, Hsuan Chou, David H Funk, John K Jackson, Bernard W Sweeney, David B Buchwalter
Understanding species' thermal limits and their physiological determinants is critical in light of climate change and other human activities that warm freshwater ecosystems. Here, we ask whether oxygen limitation determines the chronic upper thermal limits in larvae of the mayfly Neocloeon triangulifer, an emerging model for ecological and physiological studies. Our experiments are based on a robust understanding of the upper acute (∼40°C) and chronic thermal limits of this species (>28°C, ≤30°C) derived from full life cycle rearing experiments across temperatures...
July 15, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28716817/pi3k-gamma-delta-and-notch1-cross-regulate-pathways-that-define-the-t-cell-acute-lymphoblastic-leukemia-disease-signature
#10
Evgeni Efimenko, Utpal P Davé, Irina V Lebedeva, Yao Shen, Maria J Sanchez-Quintero, Daniel Diolaiti, Andrew Kung, Brian J Lannutti, Jianchung Chen, Ronald Realubit, Zoya Niatsetskiya, Vadim Ten, Charles Karan, Xi Chen, Andrea Califano, Thomas G Diacovo
PI3K/AKT and NOTCH1 signaling pathways are frequently dysregulated in T-cell acute lymphoblastic leukemias (T-ALL). Although we have shown that the combined activities of the class I PI3K isoforms p110γ and p110δ play a major role in the development and progression of PTEN null T-ALL, it has yet to be determined whether their contribution to leukemogenic programing is unique from that associated with NOTCH1 activation. Using a Lmo2-driven mouse model of T-ALL in which both the PI3K/AKT and NOTCH1 pathways are aberrantly upregulated, we now demonstrate that the combined activities of PI3Kγ/δ have both overlapping and distinct roles from NOTCH1 in generating T-ALL disease signature and in promoting tumor cell growth...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28716632/mitochondrial-estrogen-receptors-as-a-vulnerability-factor-of-chronic-stress-and-mediator-of-fluoxetine-treatment-in-female-and-male-rat-hippocampus
#11
Miroslav Adzic, Milos Mitic, Marija Radojcic
Depression is a disease of an abnormal brain energy metabolism also marked with increased apoptosis in specific brain regions. Mounting evidence indicates that the mitochondrial oxidative phosphorylation and apoptosis are novel targets for the actions of estrogen receptors (ERs). In this study, we examined the effects of antidepressant (AD) fluoxetine (FLU) treatment on the mitochondrial ER alpha (ERα), ER beta (total and phospo-pERβ) and their association with cytochrome c (cyt c) oxidase activity and apoptotic Bcl2/Bax-molecules in the hippocampal mitochondria of chronically isolated (CPSI) female and male rats depicting depression...
July 14, 2017: Brain Research
https://www.readbyqxmd.com/read/28712849/structure-function-and-mechanism-of-proline-utilization-a-puta
#12
REVIEW
Li-Kai Liu, Donald F Becker, John J Tanner
Proline has important roles in multiple biological processes such as cellular bioenergetics, cell growth, oxidative and osmotic stress response, protein folding and stability, and redox signaling. The proline catabolic pathway, which forms glutamate, enables organisms to utilize proline as a carbon, nitrogen, and energy source. FAD-dependent proline dehydrogenase (PRODH) and NAD(+)-dependent glutamate semialdehyde dehydrogenase (GSALDH) convert proline to glutamate in two sequential oxidative steps. Depletion of PRODH and GSALDH in humans leads to hyperprolinemia, which is associated with mental disorders such as schizophrenia...
July 13, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28711594/hepatic-mitochondrial-bioenergetics-in-aged-c57bl-6-mice-exhibit-delayed-recovery-from-severe-burn-injury
#13
Christopher Auger, Thibacg Sivayoganathan, Abdikarim Abdullahi, Alexandra Parousis, Marc G Jeschke
Severe burn injuries initiate a cascade of downstream events, culminating in multiple organ dysfunction, sepsis, and even death. The elderly are in particular vulnerable to such outcomes, due primarily to a scarcity of knowledge on trauma progression at the biomolecular level in this population. Mitochondria, the cellular powerhouses, have been increasingly scrutinized recently for their contribution to trauma outcomes. We hypothesized that elderly have a worse outcome compared to adult patients due to failed recovery of hepatic mitochondria...
July 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28709769/exploring-the-mitochondrial-microrna-import-pathway-through-polynucleotide-phosphorylase-pnpase
#14
Danielle L Shepherd, Quincy A Hathaway, Mark V Pinti, Cody E Nichols, Andrya J Durr, Shruthi Sreekumar, Kristen M Hughes, Seth M Stine, Ivan Martinez, John M Hollander
Cardiovascular disease is the primary cause of mortality for individuals with type 2 diabetes mellitus. During the diabetic condition, cardiovascular dysfunction can be partially attributed to molecular changes in the tissue, including alterations in microRNA (miRNA) interactions. MiRNAs have been reported in the mitochondrion and their presence may influence cellular bioenergetics, creating decrements in functional capacity. In this study, we examined the roles of Argonaute 2 (Ago2), a protein associated with cytosolic and mitochondrial miRNAs, and Polynucleotide Phosphorylase (PNPase), a protein found in the inner membrane space of the mitochondrion, to determine their role in mitochondrial miRNA import...
July 11, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28708972/uv-irradiation-of-skin-enhances-glycolytic-flux-and-reduces-migration-capabilities-in-bone-marrow-differentiated-dendritic-cells
#15
Terence A McGonigle, Kevin N Keane, Simon Ghaly, Kim W Carter, Denise Anderson, Naomi M Scott, Helen S Goodridge, Amy Dwyer, Eloise Greenland, Fiona J Pixley, Philip Newsholme, Prue H Hart
A systemic immunosuppression follows UV irradiation of the skin of humans and mice. In this study, dendritic cells (DCs) differentiating from the bone marrow of UV-irradiated mice had a reduced ability to migrate toward the chemokine (C-C motif) ligand 21. Fewer DCs also accumulated in the peritoneal cavity of UV-chimeric mice (ie, mice transplanted with bone marrow from UV-irradiated mice) after injection of an inflammatory stimulus into that site. We hypothesized that different metabolic states underpin altered DC motility...
July 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28701793/the-mir-29-transcriptome-in-endocrine-sensitive-and-resistant-breast-cancer-cells
#16
Penn Muluhngwi, Negin Alizadeh-Rad, Stephany L Vittitow, Ted S Kalbfleisch, Carolyn M Klinge
Aberrant microRNA expression contributes to breast cancer progression and endocrine resistance. We reported that although tamoxifen stimulated miR-29b-1/a transcription in tamoxifen (TAM)-resistant breast cancer cells, ectopic expression of miR-29b-1/a did not drive TAM-resistance in MCF-7 breast cancer cells. However, miR-29b-1/a overexpression significantly repressed TAM-resistant LCC9 cell proliferation, suggesting that miR-29b-1/a is not mediating TAM resistance but acts as a tumor suppressor in TAM-resistant cells...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698153/curcumin-prevents-cisplatin-induced-renal-alterations-in-mitochondrial-bioenergetics-and-dynamic
#17
Bibiana Ortega-Domínguez, Omar Emiliano Aparicio-Trejo, Fernando E García-Arroyo, Juan Carlos León-Contreras, Edilia Tapia, Eduardo Molina-Jijón, Rogelio Hernández-Pando, Laura Gabriela Sánchez-Lozada, Diana Barrera-Oviedo, José Pedraza-Chaverri
Cisplatin is widely used as chemotherapeutic agent for treatment of diverse types of cancer, however, acute kidney injury (AKI) is an important side effect of this treatment. Diverse mechanisms have been involved in cisplatin-induced AKI, such as oxidative stress, apoptosis and mitochondrial damage. On the other hand, curcumin is a polyphenol extracted from the rhizome of Curcuma longa L. Previous studies have shown that curcumin protects against the cisplatin-induced AKI; however, it is unknown whether curcumin can reduce alterations in mitochondrial bioenergetics and dynamic in this model...
July 8, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28695536/molecular-mechanisms-underlying-the-anti-depressant-effects-of-resveratrol-a-review
#18
REVIEW
Marcos Roberto de Oliveira, Aline Lukasievicz Chenet, Adriane Ribeiro Duarte, Giselli Scaini, João Quevedo
Major depression is a public health problem, affecting 121 million people worldwide. Patients suffering from depression present high rates of morbidity, causing profound economic and social impacts. Furthermore, patients with depression present cognitive impairments, which could influence on treatment adherence and long-term outcomes. The pathophysiology of major depression is not completely understood yet but involves reduced levels of monoamine neurotransmitters, bioenergetics, and redox disturbances, as well as inflammation and neuronal loss...
July 10, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28694655/antioxidant-dietary-approach-in-treatment-of-fatty-liver-new-insights-and-updates
#19
REVIEW
Alessandra Ferramosca, Mariangela Di Giacomo, Vincenzo Zara
Non-alcoholic fatty liver disease (NAFLD) is a common clinicopathological condition, encompassing a range of conditions caused by lipid deposition within liver cells. To date, no approved drugs are available for the treatment of NAFLD, despite the fact that it represents a serious and growing clinical problem in the Western world. Identification of the molecular mechanisms leading to NAFLD-related fat accumulation, mitochondrial dysfunction and oxidative balance impairment facilitates the development of specific interventions aimed at preventing the progression of hepatic steatosis...
June 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28689661/nuclear-acetyl-coa-production-by-acly-promotes-homologous-recombination
#20
Sharanya Sivanand, Seth Rhoades, Qinqin Jiang, Joyce V Lee, Joseph Benci, Jingwen Zhang, Salina Yuan, Isabella Viney, Steven Zhao, Alessandro Carrer, Michael J Bennett, Andy J Minn, Aalim M Weljie, Roger A Greenberg, Kathryn E Wellen
While maintaining the integrity of the genome and sustaining bioenergetics are both fundamental functions of the cell, potential crosstalk between metabolic and DNA repair pathways is poorly understood. Since histone acetylation plays important roles in DNA repair and is sensitive to the availability of acetyl coenzyme A (acetyl-CoA), we investigated a role for metabolic regulation of histone acetylation during the DNA damage response. In this study, we report that nuclear ATP-citrate lyase (ACLY) is phosphorylated at S455 downstream of ataxia telangiectasia mutated (ATM) and AKT following DNA damage...
July 20, 2017: Molecular Cell
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