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https://www.readbyqxmd.com/read/29161091/dealing-with-stress-defective-metabolic-adaptation-in-chronic-obstructive-pulmonary-disease-pathogenesis
#1
Charalambos Michaeloudes, Pankaj K Bhavsar, Sharon Mumby, Kian Fan Chung, Ian M Adcock
The mitochondrion is the main site of energy production and a hub of key signaling pathways. It is also central in stress-adaptive response due to its dynamic morphology and ability to interact with other organelles. In response to stress, mitochondria fuse into networks to increase bioenergetic efficiency and protect against oxidative damage. Mitochondrial damage triggers segregation of damaged mitochondria from the mitochondrial network through fission and their proteolytic degradation by mitophagy. Post-translational modifications of the mitochondrial proteome and nuclear cross-talk lead to reprogramming of metabolic gene expression to maintain energy production and redox balance...
November 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29160846/a-triphenylphosphonium-functionalized-mitochondriotropic-nanocarrier-for-efficient-co-delivery-of-doxorubicin-and-chloroquine-and-enhanced-antineoplastic-activity
#2
Katerina N Panagiotaki, Zili Sideratou, Spiros A Vlahopoulos, Maria Paravatou-Petsotas, Michael Zachariadis, Nikolas Khoury, Vassilis Zoumpourlis, Dimitris Tsiourvas
Drug delivery systems that target subcellular organelles and, in particular, mitochondria are considered to have great potential in treating disorders that are associated with mitochondrial dysfunction, including cancer or neurodegenerative diseases. To this end, a novel hyperbranched mitochondriotropic nanocarrier was developed for the efficient co-delivery of two different (both in chemical and pharmacological terms) bioactive compounds. The carrier is based on hyperbranched poly(ethyleneimine) functionalized with triphenylphosphonium groups that forms ~100 nm diameter nanoparticles in aqueous media and can encapsulate doxorubicin (DOX), a well-known anti-cancer drug, and chloroquine (CQ), a known chemosensitizer with arising potential in anticancer medication...
November 21, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/29160745/the-unveiling-of-the-warburg-effect-and-the-inscribed-innovative-approach-to-a-radical-non-toxic-anticancer-therapy
#3
Olivia Crociani, Ilaria Marzi, Maria Grazia Cipolleschi, Antonella Mannini, Massimo Contini, Massimo Olivotto
The purpose of this research has been deciphering the Warburg paradox, the biochemical enigma unsolved since 1923. This paradox consists of the aerobic pyruvate conversion to lactate brought about by anaplastic cancer, through the metabolic pathway known as aerobic glycolysis. This pathway implies a heavy energetic waste. We solved the enigma by demonstrating that its specific character, i.e. the forced aerobic lactate exportation, represents a crucial metabolic device to counteract the cytotoxic effect produced by an excess of pyruvate at the connection of glycolysis with the Krebs cycle...
November 21, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29159707/propionyl-coa-carboxylase-pcca-1-and-pccb-1-gene-deletions-in-caenorhabditis-elegans-globally-impair-mitochondrial-energy-metabolism
#4
Kimberly A Chapman, Julian Ostrovsky, Meera Rao, Stephen D Dingley, Erzsebet Polyak, Marc Yudkoff, Rui Xiao, Michael J Bennett, Marni J Falk
Propionic acidemia (PA) is a classical inborn error of metabolism with high morbidity that results from the inability of the propionyl-CoA carboxylase (PCC) enzyme to convert propionyl-CoA to methylmalonyl-CoA. PA is inherited in an autosomal recessive fashion due to functional loss of both alleles of either PCCA or PCCB. These genes are highly conserved across evolutionarily diverse species and share extensive similarity with pcca-1 and pccb-1 in the nematode, Caenorhabditis elegans. Here, we report the global metabolic effects of deletion in a single PCC gene, either pcca-1 or pccb-1, in C...
November 20, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29158815/tethering-interleukin-22-to-apolipoprotein-a-i-ameliorates-mice-from-acetaminophen-induced-liver-injury
#5
Wei Chen, Xuyao Zhang, Jiajun Fan, Wenjing Zai, Jingyun Luan, Yubin Li, Shaofei Wang, Qicheng Chen, Yichen Wang, Yanxu Liang, Dianwen Ju
Increasing evidence indicates that interleukin-22 (IL-22) holds tremendous potential as a protective agent in preventing liver injury, but its pleiotropic effects and pathogenic role in carcinogenesis, rheumatoid arthritis and psoriasis restrict its systemic application. Here, we first developed a nanoparticle (liposIA) as a liver-targeted agent through IL-22 tethered to apolipoprotein A-I (ApoA-I) in a gene therapy vector. LiposIA was prepared using thin film dispersion method and the complexes exhibited desirable nanoparticle size, fine polydisperse index, highly efficient transfection, and excellent serum and storage stability...
2017: Theranostics
https://www.readbyqxmd.com/read/29146241/cardiac-progenitor-cells-activated-by-mitochondrial-delivery-of-resveratrol-enhance-the-survival-of-a-doxorubicin-induced-cardiomyopathy-mouse-model-via-the-mitochondrial-activation-of-a-damaged-myocardium
#6
Jiro Abe, Yuma Yamada, Atsuhito Takeda, Hideyoshi Harashima
It has been reported that transplanting native cells would lack efficiency without producing artificial cell-tissue, due to the exaggerated oxidative stress in doxorubicin-induced cardiomyopathy. We attempted to activate cardiac progenitor cells (CPCs) by delivering resveratrol to mitochondria using a mitochondrial drug delivery system (MITO-Porter system). We first evaluated the viability of H9c2 cells (a cardio myoblast cell line) after doxorubicin treatment, where H9c2 cells were co-cultured with or without the mitochondria activated CPCs (referred to herein as MITO cell)...
November 14, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29145496/insights-into-soybean-transcriptome-reconfiguration-under-hypoxic-stress-functional-regulatory-structural-and-compositional-characterization
#7
Thiago J Nakayama, Fabiana A Rodrigues, Norman Neumaier, Juliana Marcolino-Gomes, Hugo B C Molinari, Thaís R Santiago, Eduardo F Formighieri, Marcos F Basso, José R B Farias, Beatriz M Emygdio, Ana C B de Oliveira, Ângela D Campos, Aluízio Borém, Frank G Harmon, Liliane M Mertz-Henning, Alexandre L Nepomuceno
Soybean (Glycine max) is one of the major crops worldwide and flooding stress affects the production and expansion of cultivated areas. Oxygen is essential for mitochondrial aerobic respiration to supply the energy demand of plant cells. Because oxygen diffusion in water is 10,000 times lower than in air, partial (hypoxic) or total (anoxic) oxygen deficiency is important component of flooding. Even when oxygen is externally available, oxygen deficiency frequently occurs in bulky, dense or metabolically active tissues such as phloem, meristems, seeds, and fruits...
2017: PloS One
https://www.readbyqxmd.com/read/29143843/mitochondria-targetable-carbon-quantum-dots-for-differentiating-cancerous-cells-from-normal-cells
#8
Ge Gao, Yao-Wen Jiang, Jingjing Yang, Fu-Gen Wu
In this study, a series of fluorescent carbon quantum dots (or carbon dots, CDs) with inherent mitochondrial targeting/imaging and cancerous/normal cell differentiation capabilities were prepared by a one-pot solvothermal treatment of glycerol and a silane molecule. Glycerol acted as a solvent and carbon source, and the silane molecule acted as a passivation agent. The as-prepared CDs could specifically and stably (for at least 24 h) visualize mitochondria of various types of cells without the introduction of mitochondria-targeting ligands (such as triphenylphosphonium)...
November 16, 2017: Nanoscale
https://www.readbyqxmd.com/read/29143658/a-key-enzyme-of-animal-steroidogenesis-can-function-in-plants-enhancing-their-immunity-and-accelerating-the-processes-of-growth-and-development
#9
George V Shpakovski, Svetlana G Spivak, Irina N Berdichevets, Olga G Babak, Svetlana V Kubrak, Alexander V Kilchevsky, Andrey V Aralov, Ivan Yu Slovokhotov, Dmitry G Shpakovski, Ekaterina N Baranova, Marat R Khaliluev, Elena K Shematorova
BACKGROUND: The initial stage of the biosynthesis of steroid hormones in animals occurs in the mitochondria of steroidogenic tissues, where cytochrome P450SCC (CYP11A1) encoded by the CYP11A1 gene catalyzes the conversion of cholesterol into pregnenolone - the general precursor of all the steroid hormones, starting with progesterone. This stage is missing in plants where mitochondrial cytochromes P450 (the mito CYP clan) have not been found. Generating transgenic plants with a mitochondrial type P450 from animals would offer an interesting option to verify whether plant mitochondria could serve as another site of P450 monooxygenase reaction for the steroid hormones biosynthesis...
November 14, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/29143438/protective-effects-of-coenzyme-q10-nanoparticles-on-dichlorvos-induced-hepatotoxicity-and-mitochondrial-lysosomal-injury
#10
Aziz Eftekhari, Elham Ahmadian, Aida Azami, Mohammad Johari-Ahar, Mohammad Ali Eghbal
Development of biocompatible antioxidant nanoparticles for xenobiotic-induced liver disease treatment by oral or parenteral administration is of great interest in medicine. In the current study, we demonstrate the protective effects of coenzyme Q10 nanoparticles (CoQ10-NPs) on hepatotoxicity induced by dichlorvos (DDVP) as an organophosphate. Although CoQ10 is an efficient antioxidant, its poor bioavailability has limited the applications of this useful agent. First, CoQ10-NPs were prepared then characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM)...
November 16, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29138502/crystal-structures-of-the-mitochondrial-deacylase-sirtuin-4-reveal-isoform-specific-acyl-recognition-and-regulation-features
#11
Martin Pannek, Zeljko Simic, Matthew Fuszard, Marat Meleshin, Dante Rotili, Antonello Mai, Mike Schutkowski, Clemens Steegborn
Sirtuins are evolutionary conserved NAD(+)-dependent protein lysine deacylases. The seven human isoforms, Sirt1-7, regulate metabolism and stress responses and are considered therapeutic targets for aging-related diseases. Sirt4 locates to mitochondria and regulates fatty acid metabolism and apoptosis. In contrast to the mitochondrial deacetylase Sirt3 and desuccinylase Sirt5, no prominent deacylase activity and structural information are available for Sirt4. Here we describe acyl substrates and crystal structures for Sirt4...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29136592/human-sirtuin-3-sirt3-deacetylates-histone-h3-lysine-56-to-promote-nonhomologous-end-joining-repair
#12
Amrita Sengupta, Devyani Haldar
Human sirtuin 3 (SIRT3) is a conserved NAD(+) dependent deacetylase, which functions in important cellular processes including transcription, metabolism, oxidative stress response. It is a robust mitochondrial deacetylase; however, few studies have indicated its nuclear functions. Here we report interaction of SIRT3 with core histones and identified acetylated histone H3 lysine 56 (H3K56ac) as its novel substrate, in addition to known substrates acetylated H4K16 and H3K9. Further, we showed in response to DNA damage SIRT3 localizes to the repair foci colocalizing with γH2AX and nonhomologous end joining (NHEJ) marker p53-binding protein 1 (53BP1)...
November 8, 2017: DNA Repair
https://www.readbyqxmd.com/read/29135280/factors-affecting-mouse-somatic-cell-nuclear-reprogramming-by-rabbit-ooplasms
#13
Xia Huang, Lili Song, Zhiyan Zhan, Haihui Gu, Haizhong Feng, Yanxin Li
Successful development of interspecies somatic cell nuclear transfer (iSCNT) embryos depends on compatibilities between ooplasmic and nuclear components. However, the mechanisms by which the compatibilities are regulated are still unknown. In this study, using mouse Oct4-green fluorescent protein (GFP) cells as donors and rabbit oocytes as recipients, we show that Oct4 and other pluripotency related genes were reactivated in some of mouse-rabbit iSCNT embryos, which could also activate Oct4 promoter-driven GFP reporter gene expression...
November 14, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/29133864/effects-of-microgravity-on-osteoblast-mitochondria-a-proteomic-and-metabolomics-profile
#14
Anna Michaletti, Magda Gioia, Umberto Tarantino, Lello Zolla
The response of human primary osteoblasts exposed to simulated microgravity has been investigated and analysis of metabolomic and proteomic profiles demonstrated a prominent dysregulation of mitochondrion homeostasis. Gravitational unloading treatment induced a decrease in mitochondrial proteins, mainly affecting efficiency of the respiratory chain. Metabolomic analysis revealed that microgravity influenced several metabolic pathways; stimulating glycolysis and the pentose phosphate pathways, while the Krebs cycle was interrupted at succinate-fumarate transformation...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29132417/quantifying-mitochondrial-dna-copy-number-using-robust-regression-to-interpret-real-time-pcr-results
#15
Paulo Refinetti, David Warren, Stephan Morgenthaler, Per O Ekstrøm
BACKGROUND: Real time PCR (rtPCR) is a quantitative assay to determine the relative DNA copy number in a sample versus a reference. The [Formula: see text] method is the standard for the analysis of the output data generated by an rtPCR experiment. We developed an alternative based on fitting a robust regression to the rtPCR signal. This new data analysis tool reduces potential biases and does not require all of the compared DNA fragments to have the same PCR efficiency. RESULTS: Comparing the two methods when analysing 96 identical PCR preparations showed similar distributions of the estimated copy numbers...
November 13, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29132331/adaptation-of-the-goldenbraid-modular-cloning-system-and-creation-of-a-toolkit-for-the-expression-of-heterologous-proteins-in-yeast-mitochondria
#16
Ana Pérez-González, Ryan Kniewel, Marcel Veldhuizen, Hemant K Verma, Mónica Navarro-Rodríguez, Luis M Rubio, Elena Caro
BACKGROUND: There is a need for the development of synthetic biology methods and tools to facilitate rapid and efficient engineering of yeast that accommodates the needs of specific biotechnology projects. In particular, the manipulation of the mitochondrial proteome has interesting potential applications due to its compartmentalized nature. One of these advantages resides in the fact that metalation occurs after protein import into mitochondria, which contains pools of iron, zinc, copper and manganese ions that can be utilized in recombinant metalloprotein metalation reactions...
November 13, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/29130633/the-mitochondrial-metabolic-reprogramming-agent-trimetazidine-as-an-exercise-mimetic-in-cachectic-c26-bearing-mice
#17
Francesca Molinari, Fabrizio Pin, Stefania Gorini, Sergio Chiandotto, Laura Pontecorvo, Fabio Penna, Emanuele Rizzuto, Simona Pisu, Antonio Musarò, Paola Costelli, Giuseppe Rosano, Elisabetta Ferraro
BACKGROUND: Cancer cachexia is characterized by muscle depletion and exercise intolerance caused by an imbalance between protein synthesis and degradation and by impaired myogenesis. Myofibre metabolic efficiency is crucial so as to assure optimal muscle function. Some drugs are able to reprogram cell metabolism and, in some cases, to enhance metabolic efficiency. Based on these premises, we chose to investigate the ability of the metabolic modulator trimetazidine (TMZ) to counteract skeletal muscle dysfunctions and wasting occurring in cancer cachexia...
November 11, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29130533/liver-mitochondrial-oxygen-consumption-and-efficiency-of-milk-production-in-lactating-holstein-cows-supplemented-with-copper-manganese-and-zinc
#18
G Acetoze, J Champagne, J J Ramsey, H A Rossow
The objective of this study was to examine the relationship between mitochondrial proton leak and feed efficiency with supplementation of different levels of Cu, Mn and Zn (Bioplex, Alltech) at levels above Nutrient Requirements of Dairy Cattle (NRC, 2001). Milk yield and composition, mineral excretion in milk and faeces, feed efficiency and liver mitochondrial proton leak were measured in 60 Holstein dairy cows at approximately 70 days in milk on a commercial dairy. Treatments reflect total Cu, Mn and Zn intake/day and are as follows: (i) High: 444 mg/day Cu, 3492 mg/day Mn, 2234 mg/day Zn; (ii) Med: 436 mg/day Cu, 3002 mg/day Mn, 2047 mg/day Zn; (iii) Low: 420 mg/day Cu, 2764 mg/day Mn, 2186 mg/day Zn; (iv) LowMn: 391 mg/day Cu, 2617 mg/day Mn, 1849 mg/day Zn; and (v) Control: 264 mg/day Cu, 2850 mg/day Mn, 1593 mg/day Zn...
November 11, 2017: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/29129912/reflective-imaging-improves-spatiotemporal-resolution-and-collection-efficiency-in-light-sheet-microscopy
#19
Yicong Wu, Abhishek Kumar, Corey Smith, Evan Ardiel, Panagiotis Chandris, Ryan Christensen, Ivan Rey-Suarez, Min Guo, Harshad D Vishwasrao, Jiji Chen, Jianyong Tang, Arpita Upadhyaya, Patrick J La Riviere, Hari Shroff
Light-sheet fluorescence microscopy (LSFM) enables high-speed, high-resolution, and gentle imaging of live specimens over extended periods. Here we describe a technique that improves the spatiotemporal resolution and collection efficiency of LSFM without modifying the underlying microscope. By imaging samples on reflective coverslips, we enable simultaneous collection of four complementary views in 250 ms, doubling speed and improving information content relative to symmetric dual-view LSFM. We also report a modified deconvolution algorithm that removes associated epifluorescence contamination and fuses all views for resolution recovery...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29128845/mitochondrial-alkaline-ph-responsive-drug-release-mediated-by-celastrol-loaded-glycolipid-like-micelles-for-cancer-therapy
#20
Yanan Tan, Yun Zhu, Yue Zhao, Lijuan Wen, Tingting Meng, Xuan Liu, Xiqin Yang, Suhuan Dai, Hong Yuan, Fuqiang Hu
Mitochondria, crucial regulators of inducing tumor cells apoptosis, can be treated as the prime target for tumor therapy. The selective and responsive release of proapoptotic therapeutics into mitochondria may notably improve antitumor efficiency. Herein, (4-Carboxybutyl) triphenylphosphonium bromide (CTPP), a lipophilic cation, was conjugated with glucolipid-like conjugates (CSOSA) to produce mitochondria-targeted conjugates (CTPP-CSOSA). Loading with weakly acidic drug Celastrol (Cela), CTPP-CSOSA/Cela micelles could selectively respond to mitochondrial alkaline pH (pH 8...
July 31, 2017: Biomaterials
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