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https://www.readbyqxmd.com/read/28716817/pi3k-gamma-delta-and-notch1-cross-regulate-pathways-that-define-the-t-cell-acute-lymphoblastic-leukemia-disease-signature
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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 1, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28688322/blood-based-bioenergetic-profiling-a-readout-of-systemic-bioenergetic-capacity-that-is-related-to-differences-in-body-composition
#12
EDITORIAL
Anthony J A Molina
No abstract text is available yet for this article.
June 30, 2017: Redox Biology
https://www.readbyqxmd.com/read/28688222/assembly-pathway-of-a-bacterial-complex-iron-sulfur-molybdoenzyme
#13
REVIEW
Stephana J Cherak, Raymond J Turner
Protein folding and assembly into macromolecule complexes within the living cell are complex processes requiring intimate coordination. The biogenesis of complex iron sulfur molybdoenzymes (CISM) requires use of a system specific chaperone - a redox enzyme maturation protein (REMP) - to help mediate final folding and assembly. The CISM dimethyl sulfoxide (DMSO) reductase is a bacterial oxidoreductase that utilizes DMSO as a final electron acceptor for anaerobic respiration. The REMP DmsD strongly interacts with DMSO reductase to facilitate folding, cofactor-insertion, subunit assembly and targeting of the multi-subunit enzyme prior to membrane translocation and final assembly and maturation into a bioenergetic catalytic unit...
July 8, 2017: Biomolecular Concepts
https://www.readbyqxmd.com/read/28688166/triheptanoin-for-the-treatment-of-brain-energy-deficit-a-14-year-experience
#14
REVIEW
Fanny Mochel
Triheptanoin is an odd-chain triglyceride with anaplerotic properties-that is, replenishing the pool of metabolic intermediates in the Krebs cycle. Unlike even-chain fatty acids metabolized to acetyl-CoA only, triheptanoin can indeed provide both acetyl-CoA and propionyl-CoA, two key carbon sources for the Krebs cycle. Triheptanoin was initially used in patients with long-chain fatty acid oxidation disorders. The first demonstration of the possible benefit of triheptanoin for brain energy deficit came from a patient with pyruvate carboxylase deficiency, a severe metabolic disease that affects anaplerosis in the brain...
July 8, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28687629/muscling-in-on-mitochondrial-sexual-dimorphism-role-of-mitochondrial-dimorphism-in-skeletal-muscle-health-and-disease
#15
Gareth A Nye, Giorgos K Sakellariou, Hans Degens, Adam P Lightfoot
Mitochondria are no longer solely regarded as the cellular powerhouse; instead, they are now implicated in mediating a wide-range of cellular processes, in the context of health and disease. A recent article in Clinical Science, Ventura-Clapier et al. highlights the role of sexual dimorphism in mitochondrial function in health and disease. However, we feel the authors have overlooked arguably one of the most mitochondria-rich organs in skeletal muscle. Many studies have demonstrated that mitochondria have a central role in mediating the pathogenesis of myopathologies...
August 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28685841/krebs-cycle-rewired-for-macrophage-and-dendritic-cell-effector-functions
#16
REVIEW
D G Ryan, L A O'Neill
The Krebs cycle is an amphibolic pathway operating in the mitochondrial matrix of all eukaryotic organisms. In response to pro-inflammatory stimuli, macrophages and dendritic cells undergo profound metabolic remodelling to support the biosynthetic and bioenergetic requirements of the cell. Recently it has been discovered that this metabolic shift also involves the rewiring of the Krebs cycle to regulate cellular metabolic flux and the accumulation of Krebs cycle intermediates, notably, citrate, succinate and fumarate...
July 7, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28685691/metabolomics-applications-in-precision-medicine-an-oncological-perspective
#17
Leonor Puchades-Carrasco, Antonio Pineda-Lucena
Nowadays, cancer therapy remains limited by the conventional one-size-fits-all approach. In this context, treatment decisions are based on the clinical stage of disease but fail to ascertain the individual´s underlying biology and its role in driving malignancy. The identification of better therapies for cancer treatment is thus limited by the lack of sufficient data regarding the characterization of specific biochemical signatures associated with each particular cancer patient or group of patients. Metabolomics approaches promise a better understanding of cancer, a disease characterized by significant alterations in bioenergetic metabolism, by identifying changes in the pattern of metabolite expression in addition to changes in the concentration of individual metabolites as well as alterations in biochemical pathways...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28684211/age-related-accumulation-of-phosphorylated-mitofusin-2-protein-in-retinal-ganglion-cells-correlates-with-glaucoma-progression
#18
Mary P Nivison, Nolan G Ericson, Virginia M Green, Jason H Bielas, Jean S Campbell, Philip J Horner
Dysregulation of axonal bioenergetics is likely a key mechanism in the initiation and progression of age-related neurodegenerative diseases. Glaucoma is a quintessential neurodegenerative disorder characterized by progressive deterioration of the optic nerve (ON) and eventual death of retinal ganglion cells (RGCs). Age and elevation of intraocular pressure are key risk factors in glaucoma, but the common early hallmarks of decreased axonal transport and increased bioenergetic vulnerability likely underlie disease initiation...
July 3, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28683280/ancillary-activity-beyond-core-metabolism-in-immune-cells
#19
REVIEW
Daniel J Puleston, Matteo Villa, Erika L Pearce
Immune cell function and fate are intimately linked to engagement of metabolic pathways. The contribution of core metabolic pathways to immune cell bioenergetics has been vigorously investigated in recent years. However, precisely how other peripheral metabolic pathways support immune cells beyond energy generation is less well understood. Here we survey the literature and highlight recent advances in our understanding of several ancillary metabolic pathways and how they support processes beyond ATP production and ultimately contribute to protective immunity...
July 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28682633/cost-of-tolerance-physiological-consequences-of-evolved-resistance-to-inhabit-a-polluted-environment-in-teleost-fish-fundulus-heteroclitus
#20
Nishad Jayasundara, Pani W Fernando, Joshua S Osterberg, Kristina M Cammen, Thomas F Schultz, Richard T Di Giulio
Anthropogenic stressors, including pollutants, are key evolutionary drivers. It is hypothesized that rapid evolution to anthropogenic changes may alter fundamental physiological processes (e.g., energy metabolism), compromising an organism's capacity to respond to additional stressors. The Elizabeth River (ER) Superfund site represents a "natural-experiment" to explore this hypothesis in several subpopulations of Atlantic killifish that have evolved a gradation of resistance to a ubiquitous pollutant-polycyclic aromatic hydrocarbons (PAH)...
July 19, 2017: Environmental Science & Technology
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