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https://www.readbyqxmd.com/read/28132899/pathological-consequences-of-micu1-mutations-on-mitochondrial-calcium-signalling-and-bioenergetics
#1
Gauri Bhosale, Jenny Sharpe, Amanda Koh, Antonina Kouli, Gyorgy Szabadkai, Michael R Duchen
Loss of function mutations of the protein MICU1, a regulator of mitochondrial Ca(2+) uptake, cause a neuronal and muscular disorder characterised by impaired cognition, muscle weakness and an extrapyramidal motor disorder. We have shown previously that MICU1 mutations cause increased resting mitochondrial Ca(2+) concentration ([Ca(2+)]m). We now explore the functional consequences of MICU1 mutations in patient derived fibroblasts in order to clarify the underlying pathophysiology of this disorder. We propose that deregulation of mitochondrial Ca(2+) uptake through loss of MICU1 raises resting [Ca(2+)]m, initiating a futile Ca(2+) cycle, whereby continuous mitochondrial Ca(2+) influx is balanced by Ca(2+) efflux through the sodium calcium exchanger (NLCXm)...
January 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28126627/effects-of-dietary-chromium-exposure-to-rockfish-sebastes-schlegelii-are-ameliorated-by-ascorbic-acid
#2
Jun-Hwan Kim, Ju-Chan Kang
Juvenile rockfish Sebastes schlegelii (mean length 10.8±1.4cm, and mean weight 31.7±3.6g) were exposed for 4 weeks with the different levels of dietary chromium (Cr(6+)) at 0, 120 and 240mg/L and ascorbic acids (AsA) at 100, 200 and 400mg/L. Significant accumulation occurred in specific tissues and hematological parameters were altered: red blood cell count, hematocrit, and hemoglobin increased; plasma components were altered including calcium, glucose, cholesterol, total protein, glutamic oxalate transaminase, and glutamic pyruvate transaminase...
January 23, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28119059/chronic-fluoxetine-treatment-directs-energy-metabolism-towards-the-citric-acid-cycle-and-oxidative-phosphorylation-in-rat-hippocampal-nonsynaptic-mitochondria
#3
Dragana Filipović, Victor Costina, Ivana Perić, Andrijana Stanisavljević, Peter Findeisen
Fluoxetine (Flx) is the principal treatment for depression; however, the precise mechanisms of its actions remain elusive. Our aim was to identify protein expression changes within rat hippocampus regulated by chronic Flx treatment versus vehicle-controls using proteomics. Fluoxetine-hydrohloride (15 mg/kg) was administered daily to adult male Wistar rats for 3 weeks, and cytosolic and nonsynaptic mitochondrial hippocampal proteomes were analyzed. All differentially expressed proteins were functionally annotated according to biological process and molecular function using Uniprot and Blast2GO...
January 21, 2017: Brain Research
https://www.readbyqxmd.com/read/28073120/nano-pelargonidin-protects-hyperglycemic-induced-l6-cells-against-mitochondrial-dysfunction
#4
Asmita Samadder, Debojyoti Tarafdar, Suresh K Abraham, Kumaresh Ghosh, Anisur Rahman Khuda-Bukhsh
Nano-encapsulation of several natural products has become an important tool in enhancing the bioavailability of some modern drugs against many diseases. Pelargonidin is an anthocyanidin found in many fruits and vegetables. Pelargonidin is loaded with poly-lactide-co-glycolic-acid, a non-toxic biodegradable polymer, to produce nano-pelargonidin. Size, morphology, zeta potential, and planar uniformity of formulated nano-pelargonidin were determined by atomic force microscopy and dynamic light scattering. The time required for cellular entry, folds of nano-pelargonidin, and drug encapsulation efficiency of poly-lactide-co-glycolic-acid were also ascertained...
January 10, 2017: Planta Medica
https://www.readbyqxmd.com/read/28072864/1h-nmr-metabolomics-reveals-association-of-high-expression-of-inositol-1-4-5-trisphosphate-receptor-and-metabolites-in-breast-cancer-patients
#5
Aru Singh, Raj Kumar Sharma, Megha Chagtoo, Gaurav Agarwal, Nelson George, Neeraj Sinha, Madan M Godbole
1H NMR is used to detect alterations in metabolites and their linkage to metabolic processes in a number of pathological conditions including breast cancer. Inositol 1, 4, 5 trisphosphate (IP3R) receptor is an intracellular calcium channel known to regulate metabolism and cellular bioenergetics. Its expression is up regulated in a number of cancers. However, its linkage to metabolism in disease conditions has not been evaluated. This study was designed to determine the association if any, of these metabolites with altered expression of IP3R in breast cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28069436/streptozotocin-causes-neurotoxic-effect-in-cultured-cerebellar-granule-neurons
#6
Elisaveta E Genrikhs, Elena V Stelmashook, Sergey A Golyshev, Olga P Aleksandrova, Nickolay K Isaev
Streptozotocin (STZ) is a glucosamine-nitrosourea compound used for experimental simulation of sporadic Alzheimer's disease at intracerebroventricular administration in vivo. The studies of STZ influence on neurons of central nervous system performed on the primary cultures are practically absent. We have shown the application of STZ (1-5mM) in primary culture for 48h induced strong dose-dependent death in cultured cerebellar granule neurons. This toxic effect was decreased by pyruvate, insulin partially. Using the indicator Fluo-4 AM for measurements of intracellular calcium ions and tetramethylrhodamine ethyl ester (TMRE) for detection of changes of mitochondrial membrane potential in live cells we have shown that 5 h-exposure to STZ induced intensive increase of Fluo-4 and decrease TMRE fluorescence in neurons...
January 6, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28057501/cloning-and-characterization-of-pyruvate-carboxylase-gene-responsible-for-calcium-malate-overproduction-in-penicillium-viticola-152-and-its-expression-analysis
#7
Ibrar Khan, Sadia Qayyum, Shehzad Ahmed, Farhana Maqbool, Isfahan Tauseef, Kashif Syed Haleem, Zhen-Ming Chi
In this study, a pyruvate carboxylase gene (PYC) from a marine fungus Penicillium viticola 152 isolated from marine algae was cloned and characterized by using Genome Walking method. An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa. A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences...
March 20, 2017: Gene
https://www.readbyqxmd.com/read/28052355/mitochondrial-ryanodine-sensitive-ca-2-channels-of-rat-liver
#8
N I Kupynyak, O V Ikkert, S G Shlykov, L G Babich, V V Manko
To examine ryanodine-sensitive Ca(2+) channels in mitochondria of rat hepatocytes and their role in energy state of the cells via investigation of the ryanodine effect on mitochondrial membrane potential. Oxygen consumption was measured by polarography using the Clark electrode. The substrates of oxidation such as pyruvate (5mM), α-ketoglutarate (5mM), or succinate (5mM) were used. Oxidative phosphorylation was stimulated by the addition of adenosine diphosphate (200nM). Mitochondrial membrane potential was measured using a voltage-sensitive fluorescent probe tetramethylrhodamine-methyl-ester (0...
January 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/28005946/the-mitochondrial-permeability-transition-pore-regulator-cyclophilin-d-exhibits-tissue-specific-control-of-metabolic-homeostasis
#9
Rhianna C Laker, Evan P Taddeo, Yasir N Akhtar, Mei Zhang, Kyle L Hoehn, Zhen Yan
The mitochondrial permeability transition pore (mPTP) is a key regulator of mitochondrial function that has been implicated in the pathogenesis of metabolic disease. Cyclophilin D (CypD) is a critical regulator that directly binds to mPTP constituents to facilitate the pore opening. We previously found that global CypD knockout mice (KO) are protected from diet-induced glucose intolerance; however, the tissue-specific function of CypD and mPTP, particularly in the control of glucose homeostasis, has not been ascertained...
2016: PloS One
https://www.readbyqxmd.com/read/27909264/global-ablation-of-the-mitochondrial-calcium-uniporter-increases-glycolysis-in-cortical-neurons-subjected-to-energetic-stressors
#10
Matthew Nichols, Pia A Elustondo, Jordan Warford, Aruloli Thirumaran, Evgeny V Pavlov, George S Robertson
The effects of global mitochondrial calcium (Ca(2+)) uniporter (MCU) deficiency on hypoxic-ischemic (HI) brain injury, neuronal Ca(2+) handling, bioenergetics and hypoxic preconditioning (HPC) were examined. Forebrain mitochondria isolated from global MCU nulls displayed markedly reduced Ca(2+) uptake and Ca(2+)-induced opening of the membrane permeability transition pore. Despite evidence that these effects should be neuroprotective, global MCU nulls and wild-type (WT) mice suffered comparable HI brain damage...
December 1, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27833053/western-diet-enhances-intestinal-tumorigenesis-in-min-mice-associating-with-mucosal-metabolic-and-inflammatory-stress-and-loss-of-apc-heterozygosity
#11
Mikael Niku, Anne-Maria Pajari, Laura Sarantaus, Essi Päivärinta, Markus Storvik, Anu Heiman-Lindh, Santeri Suokas, Minna Nyström, Marja Mutanen
Western-type diet (WD) is a risk factor for colorectal cancer, but the underlying mechanisms are poorly understood. We investigated the interaction of WD and heterozygous mutation in the Apc gene on adenoma formation and metabolic and immunological changes in the histologically normal intestinal mucosa of Apc(Min/+) (Min/+) mice. The diet used was high in saturated fat and low in calcium, vitamin D, fiber and folate. The number of adenomas was twofold higher in the WD mice compared to controls, but adenoma size, proliferation or apoptosis did not differ...
January 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27776698/ethyl-pyruvate-modulates-delayed-paralysis-following-thoracic-aortic-ischemia-reperfusion-in-mice
#12
Bao-Ngoc Nguyen, Hassan Albadawi, Rahmi Oklu, Robert S Crawford, Mitchell P Fink, Richard P Cambria, Michael T Watkins
OBJECTIVE: Delayed paralysis is an unpredictable problem for patients undergoing complex repair of the thoracic/thoracoabdominal aorta. These experiments were designed to determine whether ethyl pyruvate (EP), a potent anti-inflammatory and antioxidant agent, might ameliorate delayed paralysis following thoracic aortic ischemia reperfusion (TAR). METHODS: C57BL6 mice were subjected to 5 minutes of thoracic aortic ischemia followed by reperfusion for up to 48 hours...
November 2016: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/27746306/direct-lactic-acid-production-from-beech-wood-by-transgenic-white-rot-fungus-phanerochaete-sordida-yk-624
#13
Toshio Mori, Hiroko Kako, Tomoki Sumiya, Hirokazu Kawagishi, Hirofumi Hirai
A lactic acid (LA)-producing strain of the hyper-lignin-degrading fungus Phanerochaete sordida YK-624 with the lactate dehydrogenase-encoding gene from Bifidobacterium longum (Blldh) was constructed. When the endogenous pyruvate decarboxylase gene-knocked down and Blldh-expressing transformant was cultured with beech wood meal, the transformant was able to successively delignify and ferment the substrate. Supplementation of calcium carbonate into the culture medium, significantly increased the level of LA accumulation...
December 10, 2016: Journal of Biotechnology
https://www.readbyqxmd.com/read/27714634/zinc-oxide-nanoparticle-induces-microglial-death-by-nadph-oxidase-independent-reactive-oxygen-species-as-well-as-energy-depletion
#14
Anuj Kumar Sharma, Vikas Singh, Ruchi Gera, Mahaveer Prasad Purohit, Debabrata Ghosh
Zinc oxide nanoparticle (ZnO-NP) is one of the most widely used engineered nanoparticles. Upon exposure, nanoparticle can eventually reach the brain through various routes, interact with different brain cells, and alter their activity. Microglia is the fastest glial cell to respond to any toxic insult. Nanoparticle exposure can activate microglia and induce neuroinflammation. Simultaneous to activation, microglial death can exacerbate the scenario. Therefore, we focused on studying the effect of ZnO-NP on microglia and finding out the pathway involved in the microglial death...
October 6, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27688055/proteomic-analysis-of-pear-pyrus-pyrifolia-ripening-process-provides-new-evidence-for-the-sugar-acid-metabolism-difference-between-core-and-mesocarp
#15
Zhen Gao, Chengjun Zhang, Meng Luo, Yusen Wu, Shuyan Duan, Jiefa Li, Lei Wang, Shiren Song, Wenping Xu, Shiping Wang, Caixi Zhang, Chao Ma
Pears are one of the most popular nutrient-rich fruits in the world. The pear core and mesocarp have significantly different metabolism, although they display similar profiles. Most strikingly, the core is more acidic in taste. Our results showed that there is more titrated acid but lower total soluble solids in the core compared to the mesocarp, and the content of citric acid was more than 17-fold higher in the core compared to the mesocarp at the ripening stage. Proteomics was used to investigate the difference between core and mesocarp tissues during "Cuiguan" pear ripening...
December 2016: Proteomics
https://www.readbyqxmd.com/read/27681178/expression-of-the-mitochondrial-calcium-uniporter-in-cardiac-myocytes-improves-impaired-mitochondrial-calcium-handling-and-metabolism-in-simulated-hyperglycemia
#16
Julieta Diaz-Juarez, Jorge Suarez, Federico Cividini, Brian T Scott, Tanja Diemer, Anzhi Dai, Wolfgang H Dillmann
Diabetic cardiomyopathy is associated with metabolic changes, including decreased glucose oxidation (Gox) and increased fatty acid oxidation (FAox), which result in cardiac energetic deficiency. Diabetic hyperglycemia is a pathophysiological mechanism that triggers multiple maladaptive phenomena. The mitochondrial Ca(2+) uniporter (MCU) is the channel responsible for Ca(2+) uptake in mitochondria, and free mitochondrial Ca(2+) concentration ([Ca(2+)]m) regulates mitochondrial metabolism. Experiments with cardiac myocytes (CM) exposed to simulated hyperglycemia revealed reduced [Ca(2+)]m and MCU protein levels...
December 1, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27651676/studies-on-clinical-signs-and-biochemical-alteration-in-pregnancy-toxemic-goats
#17
Prasannkumar R Vasava, R G Jani, H V Goswami, S D Rathwa, F B Tandel
AIM: This study was planned to reveal the clinical signs and biochemical alterations in pregnancy toxemic goats. MATERIALS AND METHODS: Blood samples were collected from 20 healthy pregnant and 45 pregnancy toxemic goats and analyzed biochemically. RESULTS: The most significant clinical findings were observed in naturally affected goats with pregnancy toxemia included anorexia, recumbency, lethargy, opisthotonos, dropped head, periodic convulsion, sweetish fruity odor from breath, apparent blindness, bloat, grinding of teeth, and frothy salivation...
August 2016: Veterinary World
https://www.readbyqxmd.com/read/27648837/microrna-138-and-microrna-25-down-regulate-mitochondrial-calcium-uniporter-causing-the-pulmonary-arterial-hypertension-cancer-phenotype
#18
Zhigang Hong, Kuang-Hueih Chen, Asish DasGupta, Francois Potus, Kimberly Dunham-Snary, Sebastien Bonnet, Lian Tian, Jennifer Fu, Sandra Breuils-Bonnet, Steeve Provencher, Danchen Wu, Jeffrey Mewburn, Mark L Ormiston, Stephen L Archer
RATIONALE: Pulmonary arterial hypertension (PAH) is an obstructive vasculopathy characterized by excessive pulmonary artery smooth muscle cell (PASMC) proliferation, migration, and apoptosis resistance. This cancer-like phenotype is promoted by increased cytosolic calcium ([Ca(2+)]cyto), aerobic glycolysis, and mitochondrial fission. OBJECTIVES: To determine how changes in mitochondrial calcium uniporter (MCU) complex (MCUC) function influence mitochondrial dynamics and contribute to PAH's cancer-like phenotype...
February 15, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27636676/effects-of-arsenic-supplementation-in-feed-on-laying-performance-arsenic-retention-of-eggs-and-organs-biochemical-indices-and-endocrine-hormones
#19
X Y Zhang, M Y Zhou, L L Li, Y J Jiang, X T Zou
1. The primary objective of this experiment was to estimate the toxic effects of arsenic (As) supplementation in feed on laying performance, As retention by eggs and organs, serum biochemical indices and endocrine hormones in laying hens. 2. A total of 320 "Jinghong Number 1" hens, 56-week-old, were randomly allocated into four treatments of four replicates with 20 layers in each. Graded arsenical was added to the basal diet in the experimental diets at As levels of 0, 17, 34 and 51 mg/kg, respectively. The trial lasted for 9 weeks including 1 week for acclimatisation...
February 2017: British Poultry Science
https://www.readbyqxmd.com/read/27621312/cardiac-ryanodine-receptor-ryr2-mediated-calcium-signals-specifically-promote-glucose-oxidation-via-pyruvate-dehydrogenase
#20
Michael J Bround, Rich Wambolt, Haoning Cen, Parisa Asghari, Razvan F Albu, Jun Han, Donald McAfee, Marc Pourrier, Nichollas E Scott, Lubos Bohunek, Jerzy E Kulpa, S R Wayne Chen, David Fedida, Roger W Brownsey, Christoph H Borchers, Leonard J Foster, Thibault Mayor, Edwin D W Moore, Michael F Allard, James D Johnson
Cardiac ryanodine receptor (Ryr2) Ca(2+) release channels and cellular metabolism are both disrupted in heart disease. Recently, we demonstrated that total loss of Ryr2 leads to cardiomyocyte contractile dysfunction, arrhythmia, and reduced heart rate. Acute total Ryr2 ablation also impaired metabolism, but it was not clear whether this was a cause or consequence of heart failure. Previous in vitro studies revealed that Ca(2+) flux into the mitochondria helps pace oxidative metabolism, but there is limited in vivo evidence supporting this concept...
November 4, 2016: Journal of Biological Chemistry
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