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Mitochondrial respiration

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https://www.readbyqxmd.com/read/28528289/platelet-hyperactivation-apoptosis-and-hypercoagulability-in-patients-with-acute-pulmonary-embolism
#1
Samin Rezania, Michael A Puskarich, Daniela N Petrusca, Evandro M Neto-Neves, Matthew T Rondina, Jeffrey A Kline
Changes in systemic redox balance can alter platelet activation and aggregation. Acute pulmonary embolism (PE) is a systematic inflammatory disease associated with mechanical shear stress, increased thrombin, catecholamines, serotonin and hemolysis, which cumulatively can hyperactivate platelets and accelerate their turnover. We tested the hypothesis that platelets from patients with moderately severe PE will show hyperstimulation and a pre-apoptotic phenotype associated with microparticles (MPs) in plasma...
May 13, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28527718/rotenone-decreases-ischemia-induced-injury-by-inhibiting-mitochondrial-permeability-transition-in-mature-brains
#2
Evelina Rekuviene, Laima Ivanoviene, Vilmante Borutaite, Ramune Morkuniene
The mitochondrial permeability transition pore (mPTP) is thought to be implicated in brain ischemia-induced cell death. Here we sought to determine whether complex I (CI) of the mitochondrial electron transfer system may be involved in regulation of mPTP opening during ischemia and whether a specific inhibitor of this complex - rotenone can protect against ischemia-induced cell death in an experimental model of total ischemia in adult rat brains. Anesthetized Wistar rats were administered a single injection of rotenone (0...
May 17, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28527697/antibiotics-induce-mitonuclear-protein-imbalance-but-fail-to-inhibit-respiration-and-nutrient-activation-in-pancreatic-%C3%AE-cells
#3
Jaime Santo-Domingo, Isabelle Chareyron, Charlotte Broenimann, Steve Lassueur, Andreas Wiederkehr
Chloramphenicol and several other antibiotics targeting bacterial ribosomes inhibit mitochondrial protein translation. Inhibition of mitochondrial protein synthesis leads to mitonuclear protein imbalance and reduced respiratory rates as confirmed here in HeLa and PC12 cells. Unexpectedly, respiration in INS-1E insulinoma cells and primary human islets was unaltered in the presence of chloramphenicol. Resting respiratory rates and glucose stimulated acceleration of respiration were also not lowered when a range of antibiotics including, thiamphenicol, streptomycin, gentamycin and doxycycline known to interfere with bacterial protein synthesis were tested...
May 17, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28527631/the-thiol-switch-c684-in-mitofusin-2-mediates-redox-induced-alterations-of-mitochondrial-shape-and-respiration
#4
Osamah Thaher, Christina Wolf, Partha Narayan Dey, Alireza Pouya, Verena Wüllner, Stefan Tenzer, Axel Methner
Mitofusin-2 (MFN2) is a GTPase in the outer mitochondrial membrane involved in the regulation of mitochondrial fusion and bioenergetics. MFN2 also plays a role in mitochondrial fusion induced by changes in the intracellular redox state. Adding oxidized glutathione (GSSG), the core cellular stress indicator, to mitochondrial preparations stimulates mitochondrial fusion by inducing disulphide bond-mediated oligomer formation of MFN2 and its homolog MFN1 which involve cysteine 684 (C684) of MFN2. Mitochondrial hyperfusion represents an adaptive stress response that confers transient protection by increasing mitochondrial ATP production but how this depends on the thiol switch C684 in MFN2 has not been investigated...
May 17, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28526448/the-catechol-o-methyltransferase-inhibitors-tolcapone-and-entacapone-uncouple-and-inhibit-the-mitochondrial-respiratory-chain-in-heparg-cells
#5
David Grünig, Andrea Felser, Jamal Bouitbir, Stephan Krähenbühl
The catechol-O-methyltransferase inhibitor tolcapone causes hepatotoxicity and mitochondrial damage in animal models. We studied the interaction of tolcapone with mitochondrial respiration in comparison to entacapone in different experimental models. In HepaRG cells (human cell-line), tolcapone decreased the ATP content (estimated IC50 100±15μM) and was cytotoxic (estimated IC50 333±45μM), whereas entacapone caused no cytotoxicity and no ATP depletion up to 200μM. Cytochrome P450 induction did not increase the toxicity of the compounds...
May 16, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28526246/impaired-mitophagy-facilitates-mitochondrial-damage-in-danon-disease
#6
Sherin I Hashem, Anne N Murphy, Ajit S Divakaruni, Matthew L Klos, Bradley C Nelson, Emily C Gault, Teisha J Rowland, Cynthia N Perry, Yusu Gu, Nancy D Dalton, William H Bradford, Eric J Devaney, Kirk L Peterson, Kenneth L Jones, Matthew R G Taylor, Ju Chen, Neil C Chi, Eric D Adler
RATIONALE: Lysosomal associated membrane protein type-2 (LAMP-2) is a highly conserved, ubiquitous protein that is critical for autophagic flux. Loss of function mutations in the LAMP-2 gene cause Danon disease, a rare X-linked disorder characterized by developmental delay, skeletal muscle weakness, and severe cardiomyopathy. We previously found that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from Danon patients exhibited significant mitochondrial oxidative stress and apoptosis...
May 16, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28524096/itraq-mitoproteome-analysis-reveals-mechanisms-of-programmed-cell-death-in-arabidopsis-thaliana-induced-by-ochratoxin-a
#7
Yan Wang, Xiaoli Peng, Zhuojun Yang, Weiwei Zhao, Wentao Xu, Junran Hao, Weihong Wu, Xiao Li Shen, Yunbo Luo, Kunlun Huang
Ochratoxin A (OTA) is one of the most common and dangerous mycotoxins in the world. Previous work indicated that OTA could elicit spontaneous HR-like lesions formation Arabidopsis thaliana, reactive oxygen species (ROS) play an important role in OTA toxicity, and their major endogenous source is mitochondria. However, there has been no evidence as to whether OTA induces directly PCD in plants until now. In this study, the presence of OTA in Arabidopsisthaliana leaves triggered accelerated respiration, increased production of mitochondrial ROS, the opening of ROS-dependent mitochondrial permeability transition pores and a decrease in mitochondrial membrane potential as well as the release of cytochrome c into the cytosol...
May 18, 2017: Toxins
https://www.readbyqxmd.com/read/28522765/exercise-training-in-tg%C3%AE-q-44-mice-during-the-progression-of-chronic-heart-failure-cardiac-vs-peripheral-soleus-muscle-impairments-to-oxidative-metabolism
#8
Bruno Grassi, Joanna Majerczak, Eleonora Bardi, Alessia Buso, Marina Comelli, Stefan Chlopicki, Magdalena Guzik, Irene Mavelli, Zenon Nieckarz, Desy Salvadego, Urszula Tyrankiewicz, Tomasz Skorka, Roberto Bottinelli, Jerzy A Zoladz, Maria Antonietta Pellegrino
Cardiac function, skeletal (soleus) muscle oxidative metabolism and the effects of exercise training were evaluated in a transgenic murine model (Tgαq*44) of chronic heart failure (CHF) during the critical period between the occurrence of an impairment of cardiac function and the stage at which overt cardiac failure ensues (i.e. from 10 to 12 months of age). Forty-eight Tgαq*44 mice and 43 wild-type (WT) FVB controls were randomly assigned to control groups and to groups undergoing 2 months of intense exercise training (spontaneous running on a instrumented wheel)...
May 18, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28515438/mitochondrial-retrograde-signaling-connects-respiratory-capacity-to-thermogenic-gene-expression
#9
Minwoo Nam, Thomas E Akie, Masato Sanosaka, Siobhan M Craige, Shashi Kant, John F Keaney, Marcus P Cooper
Mitochondrial respiration plays a crucial role in determining the metabolic state of brown adipose tissue (BAT), due to its direct roles in thermogenesis, as well as through additional mechanisms. Here, we show that respiration-dependent retrograde signaling from mitochondria to nucleus contributes to genetic and metabolic reprogramming of BAT. In mouse BAT, ablation of LRPPRC (LRP130), a potent regulator of mitochondrial transcription and respiratory capacity, triggers down-regulation of thermogenic genes, promoting a storage phenotype in BAT...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515169/osmoregulation-bioenergetics-and-oxidative-stress-in-coastal-marine-invertebrates-raising-the-questions-for-future-research
#10
REVIEW
Georgina A Rivera-Ingraham, Jehan-Hervé Lignot
Osmoregulation is by no means an energetically cheap process, and its costs have been extensively quantified in terms of respiration and aerobic metabolism. Common products of mitochondrial activity are reactive oxygen and nitrogen species, which may cause oxidative stress by degrading key cell components, while playing essential roles in cell homeostasis. Given the delicate equilibrium between pro- and antioxidants in fueling acclimation responses, the need for a thorough understanding of the relationship between salinity-induced oxidative stress and osmoregulation arises as an important issue, especially in the context of global changes and anthropogenic impacts on coastal habitats...
May 15, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28515085/regulation-of-atp-production-dependences-on-calcium-concentration-and-respiratory-state
#11
Brian D Fink, Fan Bai, Liping Yu, William I Sivitz
Nanomolar free calcium enhances oxidative phosphorylation. However, the effects over a broad concentration range, at different respiratory states, or on specific energy substrates are less clear. We examined the action of varying [Ca(2+)] over respiratory states ranging 4 to 3 on skeletal muscle mitochondrial respiration, potential, ATP production, and H2O2 production using ADP recycling to clamp external [ADP]. 450 nM calcium enhanced respiration in mitochondria energized by the complex I substrates, glutamate/malate (but not succinate) at [ADP] of 4-256 µM, but more substantially at intermediate respiratory states and not all at state 4...
May 17, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28514055/caveolin-1-deficiency-induces-premature-senescence-with-mitochondrial-dysfunction
#12
Dong-Min Yu, Seung Hee Jung, Hyoung-Tae An, Sungsoo Lee, Jin Hong, Jun Sub Park, Hyun Lee, Hwayeon Lee, Myeong-Suk Bahn, Hyung Chul Lee, Na-Kyung Han, Jesang Ko, Jae-Seon Lee, Young-Gyu Ko
Paradoxical observations have been made regarding the role of caveolin-1 (Cav-1) during cellular senescence. For example, caveolin-1 deficiency prevents reactive oxygen species-induced cellular senescence despite mitochondrial dysfunction, which leads to senescence. To resolve this paradox, we re-addressed the role of caveolin-1 in cellular senescence in human diploid fibroblasts, A549, HCT116, and Cav-1(-/-) mouse embryonic fibroblasts. Cav-1 deficiency (knockout or knockdown) induced cellular senescence via a p53-p21-dependent pathway, downregulating the expression level of the cardiolipin biosynthesis enzymes and then reducing the content of cardiolipin, a critical lipid for mitochondrial respiration...
May 17, 2017: Aging Cell
https://www.readbyqxmd.com/read/28513179/consumption-of-watermelon-juice-enriched-in-l-citrulline-and-pomegranate-ellagitannins-enhanced-metabolism-during-physical-exercise
#13
Ascension Martinez-Sanchez, Fernando Alacid, Jacobo A Rubio-Arias, Bárbara Fernandez-Lobato, Domingo J Ramos-Campo, Encarna Aguayo
L-citrulline is a non-essential amino acid precursor of arginine and indirectly a precursor of nitric oxide (NO), which is a vasodilator and increases mitochondrial respiration. On the other hand, the antioxidant pomegranate ellagitannins are precursors of urolithin A, which has been associated with mitophagy and increased muscle function. To elucidate if a single dose of watermelon enrichment with these compounds have a positive effect after a high intensity exercise (8 sets of 8 repetitions of half squat exercise), a double-blind randomized crossover in vivo study was performed in healthy male subjects (n=19)...
May 17, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28512249/p62-sqstm1-cooperates-with-hyperactive-mtorc1-to-regulate-glutathione-production-maintain-mitochondrial-integrity-and-promote-tumorigenesis
#14
Hilaire C Lam, Christian V Baglini, Alicia Llorente Lope, Andrey Parkhitko, Heng-Jia Liu, Nicola Alesi, Izabela A Malinowska, Darius Ebrahimi-Fakhari, Afshin Saffari, Jane J Yu, Ana Pereira, Damir Khabibullin, Barbara Ogorek, Julie S Nijmeh, Taylor Kavanagh, Adam Handen, Stephen Y Chan, John M Asara, William M Oldham, Maria Diaz-Meco, Jorge Moscat, Mustafa Sahin, Carmen Priolo, Elizabeth P Henske
p62/sequestosome-1 (SQSTM1) is a multifunctional adaptor protein and autophagic substrate which accumulates in cells with hyperactive mTORC1, such as kidney cells with mutations in the tumor suppressor genes TSC1 or TSC2. Here we report that p62 is a critical mediator of TSC2-driven tumorigenesis, as Tsc2+/- and Tsc2f/f Ksp-CreERT2+ mice crossed to p62-/- mice were protected from renal tumor development. Metabolic profiling revealed that depletion of p62 in Tsc2-null cells decreased intracellular glutamine, glutamate, and glutathione (GSH)...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28511992/rna-seq-analyses-reveal-that-cervical-spinal-cords-and-anterior-motor-neurons-from-amyotrophic-lateral-sclerosis-subjects-show-reduced-expression-of-mitochondrial-dna-encoded-respiratory-genes-and-rhtfam-may-correct-this-respiratory-deficiency
#15
Amy C Ladd, David G Brohawn, Ravindar R Thomas, Paula M Keeney, Stuart S Berr, Shaharyar M Khan, Francisco R Portell, Meiram Zh Shakenov, Patrick F Antkowiak, Bijoy Kundu, Nicholas Tustison, James P Bennett
Amyotrophic lateral sclerosis (ALS) is a generally fatal neurodegenerative disease of adults that produces weakness and atrophy due to dysfunction and death of upper and lower motor neurons. We used RNA-sequencing (RNA-seq) to analyze expression of all mitochondrial DNA (mtDNA)-encoded respiratory genes in ALS and CTL human cervical spinal cords (hCSC) and isolated motor neurons. We analyzed with RNA-seq mtDNA gene expression in human neural stem cells (hNSC) exposed to recombinant human mitochondrial transcription factor A (rhTFAM), visualized in 3-dimensions clustered gene networks activated by rhTFAM, quantitated their interactions with other genes and determined their gene ontology (GO) families...
May 13, 2017: Brain Research
https://www.readbyqxmd.com/read/28507314/metabolic-imaging-of-energy-metabolism-in-traumatic-brain-injury-using-hyperpolarized-1-13-c-pyruvate
#16
Stephen J DeVience, Xin Lu, Julie Proctor, Parisa Rangghran, Elias R Melhem, Rao Gullapalli, Gary M Fiskum, Dirk Mayer
Traumatic brain injury (TBI) is known to cause perturbations in the energy metabolism of the brain, but current tests of metabolic activity are only indirect markers of energy use or are highly invasive. Here we show that hyperpolarized (13)C magnetic resonance spectroscopic imaging (MRSI) can be used as a direct, non-invasive method for studying the effects of TBI on energy metabolism. Measurements were performed on rats with moderate TBI induced by controlled cortical impact on one cerebral hemisphere. Following injection of hyperpolarized [1-(13)C]pyruvate, the resulting (13)C-bicarbonate signal was found to be 24 ± 6% lower in the injured hemisphere compared with the non-injured hemisphere, while the hyperpolarized bicarbonate-to-lactate ratio was 33 ± 8% lower in the injured hemisphere...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28504706/the-mitochondrial-respiratory-chain-is-essential-for-haematopoietic-stem-cell-function
#17
Elena Ansó, Samuel E Weinberg, Lauren P Diebold, Benjamin J Thompson, Sébastien Malinge, Paul T Schumacker, Xin Liu, Yuannyu Zhang, Zhen Shao, Mya Steadman, Kelly M Marsh, Jian Xu, John D Crispino, Navdeep S Chandel
Adult and fetal haematopoietic stem cells (HSCs) display a glycolytic phenotype, which is required for maintenance of stemness; however, whether mitochondrial respiration is required to maintain HSC function is not known. Here we report that loss of the mitochondrial complex III subunit Rieske iron-sulfur protein (RISP) in fetal mouse HSCs allows them to proliferate but impairs their differentiation, resulting in anaemia and prenatal death. RISP-null fetal HSCs displayed impaired respiration resulting in a decreased NAD(+)/NADH ratio...
May 15, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28504693/cyclin-dependent-kinase-7-is-a-therapeutic-target-in-high-grade-glioma
#18
S A Greenall, Y C Lim, C B Mitchell, K S Ensbey, B W Stringer, A L Wilding, G M O'Neill, K L McDonald, D J Gough, B W Day, T G Johns
High-grade glioma (HGG) is an incurable brain cancer. The transcriptomes of cells within HGG tumors are highly heterogeneous. This renders the tumors unresponsive or able to adapt to therapeutics targeted at single pathways, thereby causing treatment failure. To overcome this, we focused on cyclin-dependent kinase 7 (CDK7), a ubiquitously expressed molecule involved in two major drivers of HGG pathogenesis: cell cycle progression and RNA polymerase-II-based transcription. We tested the activity of THZ1, an irreversible CDK7 inhibitor, on patient-derived primary HGG cell lines and ex vivo HGG patient tissue slices, using proliferation assays, microarray analysis, high-resolution respirometry, cell cycle analysis and in vivo tumor orthografts...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28502921/umbilical-cord-mscs-reverse-d-galactose-induced-hepatic-mitochondrial-dysfunction-via-activation-of-nrf2-ho-1-pathway
#19
Weihong Yan, Dong Li, Tong Chen, Guiying Tian, Panpan Zhou, Xiuli Ju
Mitochondria are the central hubs for cellular bioenergetics and are crucial to cell survival. It is well accepted that compromised mitochondrial function is linked with hepatocytes injury and contribute to progression of liver diseases. Despite the therapeutic potential of mesenchymal stem cells (MSCs) transplantation on hepatic disorders have been extensively investigated, the effects of MSCs on mitochondrial function in liver injury models remain unknown. Here we investigated the effects of treatment with umbilical cord (UC) MSC in a rat model of D-Gal induced liver injury, characterized by organ damage, oxidative stress and mitochondrial dysfunction...
May 13, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28501615/the-changes-in-glucose-metabolism-and-cell-proliferation-in-the-kidneys-of-polycystic-kidney-disease-mini-pig-models
#20
Xiaoying Lian, Jing Zhao, Xiaoyuan Wu, Yingjie Zhang, Qinggang Li, Shupeng Lin, Xue-Yuan Bai, Xiangmei Chen
The pathogenic mechanism of polycystic kidney disease (PKD) is unclear. Abnormal glucose metabolism is maybe involved in hyper-proliferation of renal cyst epithelial cells. Mini-pigs are more similar to humans than rodents and therefore, are an ideal large animal model. In this study, for the first time, we systematically investigated the changes in glucose metabolism and cell proliferation signaling pathways in the kidney tissues of chronic progressive PKD mini-pig models created by knock-outing PKD1gene. The results showed that in the kidneys of PKD mini-pigs, the glycolysis is increased and the expressions of key oxidative phosphorylation enzymes Complexes I and IV significantly decreased...
May 10, 2017: Biochemical and Biophysical Research Communications
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