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https://www.readbyqxmd.com/read/28330953/your-mitochondria-are-what-you-eat-a-high-fat-or-a-high-sucrose-diet-eliminates-metabolic-flexibility-in-isolated-mitochondria-from-rat-skeletal-muscle
#1
Wenche Jørgensen, Kasper A Rud, Ole H Mortensen, Lis Frandsen, Niels Grunnet, Bjørn Quistorff
Extreme diets consisting of either high fat (HF) or high sucrose (HS) may lead to insulin resistance in skeletal muscle, often associated with mitochondrial dysfunction. However, it is not known if these diets alter normal interactions of pyruvate and fatty acid oxidation at the level of the mitochondria. Here, we report that rat muscle mitochondria does show the normal Randle-type fat-carbohydrate interaction seen in vivo. The mechanism behind this metabolic flexibility at the level of the isolated mitochondria is a regulation of the flux-ratio: pyruvate dehydrogenase (PDH)/β-oxidation to suit the actual substrate availability, with the PDH flux as the major point of regulation...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28329008/insulin-and-diet-induced-changes-in-the-ubiquitin-modified-proteome-of-rat-liver
#2
Shilpa R Nagarajan, Amanda E Brandon, Jessie A McKenna, Harrison C Shtein, Thinh Q Nguyen, Eurwin Suryana, Philip Poronnik, Gregory J Cooney, Darren N Saunders, Andrew J Hoy
Ubiquitin is a crucial post-translational modification regulating numerous cellular processes, but its role in metabolic disease is not well characterized. In this study, we identified the in vivo ubiquitin-modified proteome in rat liver and determined changes in this ubiquitome under acute insulin stimulation and high-fat and sucrose diet-induced insulin resistance. We identified 1267 ubiquitinated proteins in rat liver across diet and insulin-stimulated conditions, with 882 proteins common to all conditions...
2017: PloS One
https://www.readbyqxmd.com/read/28323497/potential-mechanisms-underlying-cdk5-related-osteosarcoma-progression
#3
Hang-Xing Bao, Qing Bi, Yong Han, Chen Zhao, Hai Zou
OBJECTIVES: Identification of new prognostic biomarkers and therapeutic targets is of crucial importance for patients with osteosarcoma. Cyclin-dependent kinase 5 (CDK5) is overexpressed in several tumor types. However, the exact role CDK5 plays in osteosarcoma is still unknown. METHODS: In this study, we explored the association between CDK5 expression and the prognosis of osteosarcoma patients using publicly available gene expression datasets. Potential molecular mechanisms underlying its pro-malignant role in cancer progression were also discussed...
March 21, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28323243/proteomics-of-facs-sorted-heterogeneous-corynebacterium-glutamicum-populations
#4
Andreas Harst, Stefan P Albaum, Tanja Bojarzyn, Christian Trötschel, Ansgar Poetsch
The metabolic status of individual cells in microbial cultures can differ, being relevant for biotechnology, environmental and medical microbiology. However, it is hardly understood in molecular detail due to limitations of current analytical tools. Here, we demonstrate that FACS in combination with proteomics can be used to sort and analyze cell populations based on their metabolic state. A previously established GFP reporter system was used to detect and sort single Corynebacterium glutamicum cells based on the concentration of branched chain amino acids (BCAA) using FACS...
March 17, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28322849/trans-cinnamic-acid-and-xenorhabdus-szentirmaii-metabolites-synergize-the-potency-of-some-commercial-fungicides
#5
Selcuk Hazir, David I Shapiro-Ilan, Clive H Bock, Luis G Leite
Development of novel approaches for the control of fungal phytopathogens is desirable. In this study we hypothesized that the combination of commercial fungicides with certain enhancing agents could result in synergistic levels of control. Prior research has indicated that trans-cinnamic-acid (TCA), a metabolite of the bacteria Photorhabdus luminescens and metabolites of Xenorhabdus szentirmaii are particularly toxic to various phytpathogenic fungi when compared to metabolites of other Xenorhabdus or Photorhabdus spp...
March 18, 2017: Journal of Invertebrate Pathology
https://www.readbyqxmd.com/read/28322247/tricyclic-antidepressants-promote-ceramide-accumulation-to-regulate-collagen-production-in-human-hepatic-stellate-cells
#6
Jennifer Y Chen, Benjamin Newcomb, Chan Zhou, Joshua V Pondick, Sarani Ghoshal, Samuel R York, Daniel L Motola, Nicolas Coant, Jae Kyo Yi, Cungui Mao, Kenneth K Tanabe, Irina Bronova, Evgeny V Berdyshev, Bryan C Fuchs, Yusuf Hannun, Raymond T Chung, Alan C Mullen
Activation of hepatic stellate cells (HSCs) in response to injury is a key step in hepatic fibrosis, and is characterized by trans-differentiation of quiescent HSCs to HSC myofibroblasts, which secrete extracellular matrix proteins responsible for the fibrotic scar. There are currently no therapies to directly inhibit hepatic fibrosis. We developed a small molecule screen to identify compounds that inactivate human HSC myofibroblasts through the quantification of lipid droplets. We screened 1600 compounds and identified 21 small molecules that induce HSC inactivation...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28320837/the-suf-iron-sulfur-cluster-biosynthetic-system-is-essential-in-staphylococcus-aureus-and-decreased-suf-function-results-in-global-metabolic-defects-and-reduced-survival-in-human-neutrophils
#7
Christina A Roberts, Hassan M Al-Tameemi, Ameya A Mashruwala, Zuelay Rosario-Cruz, Unnati Chauhan, William E Sause, Victor J Torres, William J Belden, Jeffrey M Boyd
Staphylococcus aureus remains a causative agent for morbidity and mortality worldwide. This is, in part, a result of antimicrobial resistance highlighting the need to uncover novel antibiotic targets and discover new therapeutic agents. In the present study we explored the possibility that iron-sulfur (Fe-S) cluster synthesis is a viable antimicrobial target. RNA interference studies established that Suf (sulfur mobilization) dependent Fe-S cluster synthesis is essential in S. aureus We found that sufCDSUB were cotranscribed and suf transcription was positively influenced by sigma factor B...
March 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28319140/role-of-muscle-il-6-in-gender-specific-metabolism-in-mice
#8
Amalia Molinero, Antonio Fernandez-Perez, Aina Mogas, Mercedes Giralt, Gemma Comes, Olaya Fernandez-Gayol, Mario Vallejo, Juan Hidalgo
The aim of the present work was to further explore the physiological roles of muscle-derived IL-6. Adult-floxed and conditional skeletal muscle IL-6 knock out male and female mice were used to study energy expenditure (indirect calorimetry at rest and during treadmill exercise, and body temperature cycle during the light phase) and energy intake (response to fast/refeeding). We also evaluated the responses to leptin and the activity of the insulin signalling pathway in skeletal muscle and liver by phosphorylation of Akt at Ser 473...
2017: PloS One
https://www.readbyqxmd.com/read/28317891/hepatic-mitochondrial-dysfunction-is-a-feature-of-glycogen-storage-disease-type-ia-gsdia
#9
Benjamin L Farah, Rohit A Sinha, Yajun Wu, Brijesh K Singh, Andrea Lim, Masahiro Hirayama, Dustin J Landau, Boon Huat Bay, Dwight D Koeberl, Paul M Yen
Glycogen storage disease type Ia (GSDIa, von Gierke disease) is the most common glycogen storage disorder. It is caused by the deficiency of glucose-6-phosphatase, an enzyme which catalyses the final step of gluconeogenesis and glycogenolysis. Clinically, GSDIa is characterized by fasting hypoglycaemia and hepatic glycogen and triglyceride overaccumulation. The latter leads to steatohepatitis, cirrhosis, and the formation of hepatic adenomas and carcinomas. Currently, little is known about the function of various organelles and their impact on metabolism in GSDIa...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28316083/energy-metabolism-in-the-rat-cortex-under-thiopental-anaesthesia-measured-in-vivo-by-13-c-mrs
#10
Sarah Sonnay, João M N Duarte, Nathalie Just, Rolf Gruetter
Barbiturates, commonly used as general anaesthetics, depress neuronal activity and thus cerebral metabolism. Moreover, they are likely to disrupt the metabolic support of astrocytes to neurons, as well as the uptake of nutrients from circulation. By employing (13) C magnetic resonance spectroscopy (MRS) in vivo at high magnetic field, we characterized neuronal and astrocytic pathways of energy metabolism in the rat cortex under thiopental anaesthesia. The neuronal tricarboxylic acid (TCA) cycle rate was 0.46 ± 0...
March 19, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28316081/the-antidiabetic-drug-metformin-decreases-mitochondrial-respiration-and-tricarboxylic-acid-cycle-activity-in-cultured-primary-rat-astrocytes
#11
Michaela C Hohnholt, Eva-Maria Blumrich, Helle S Waagepetersen, Ralf Dringen
Metformin is an antidiabetic drug that is used daily by millions of patients worldwide. Metformin is able to cross the blood-brain barrier and has recently been shown to increase glucose consumption and lactate release in cultured astrocytes. However, potential effects of metformin on mitochondrial tricarboxylic acid (TCA) cycle metabolism in astrocytes are unknown. We investigated this by mapping (13) C labeling in TCA cycle intermediates and corresponding amino acids after incubation of primary rat astrocytes with [U-(13) C]glucose...
March 19, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28314371/intrauterine-growth-restriction-programs-the-hypothalamus-of-adult-male-rats-integrated-analysis-of-proteomic-and-metabolomic-data
#12
Amanda Paula Pedroso, Adriana Pereira de Souza, Ana Paula Segantine Dornellas, Lila Missae Oyama, Cláudia Maria Oller Nascimento, Gianni Mara Silva Santos, José C Rosa, Ricardo Pimenta Bertolla, Jelena Klawitter, Uwe Christians, Alexandre Keiji Tashima, Eliane Beraldi Ribeiro
Programming of hypothalamic functions regulating energy homeostasis may play a role in intrauterine growth restriction (IUGR)-induced adulthood obesity. The present study investigated the effects of IUGR on the hypothalamus proteome and metabolome of adult rats submitted to 50% protein-energy restriction throughout pregnancy. Proteomic and metabolomic analyzes were performed by data independent acquisition mass spectrometry and multiple reaction monitoring, respectively. At age 4 months, the restricted rats showed elevated adiposity, increased leptin and signs of insulin resistance...
March 17, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28306498/elevation-of-fumarate-levels-compromise-redox-control-and-viability-in-mycobacterium-tuberculosis
#13
Yong-Mo Ahn, Helena I Boshoff
In this issue of Cell Chemical Biology, Ruecker et al. (2017) show that fumarase depletion in Mycobacterium tuberculosis leads to fumarate, a TCA cycle intermediate, accumulation, causing succination of a range of thiol-containing metabolites and proteins. Fumarate is bactericidal to the pathogen, and its accumulation may enhance the bactericidal effector mechanisms of other TCA cycle intermediates that accumulate due to activation of infected macrophages.
March 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28306342/nmr-based-plasma-metabolomic-discrimination-for-male-fertility-assessment-of-rats-treated-with-eurycoma-longifolia-extracts
#14
Forough Ebrahimi, Baharudin Ibrahim, Chin-Hoe Teh, Vikneswaran Murugaiyah, Kit-Lam Chan
Male infertility is one of the leading causes of infertility which affects many couples worldwide. Semen analysis is a routine examination of male fertility status which is usually performed on semen samples obtained through masturbation that may be inconvenient to patients. Eurycoma longifolia (Tongkat Ali, TA), native to Malaysia, has been traditionally used as a remedy to boost male fertility. In our recent studies in rats, upon the administration of high-quassinoid content extracts of TA including TA water (TAW), quassinoid-rich TA (TAQR) extracts, and a low-quassinoid content extract including quassinoid-poor TA (TAQP) extract, sperm count (SC) increased in TAW- and TAQR-treated rats when compared to the TAQP-treated and control groups...
March 17, 2017: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/28303258/alterations-in-cytosolic-and-mitochondrial-u-13-c-glucose-metabolism-in-a-chronic-epilepsy-mouse-model
#15
Tanya S McDonald, Catalina Carrasco-Pozo, Mark P Hodson, Karin Borges
Temporal lobe epilepsy is a common form of adult epilepsy and shows high resistance to treatment. Increasing evidence has suggested that metabolic dysfunction contributes to the development of seizures, with previous studies indicating impairments in brain glucose metabolism. Here we aim to elucidate which pathways involved in glucose metabolism are impaired, by tracing the hippocampal metabolism of injected [U-(13)C]glucose (i.p.) during the chronic stage of the pilocarpine-status epilepticus mouse model of epilepsy...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28302489/modelling-urea-cycle-disorder-citrullinemia-type-1-with-disease-specific-ipscs
#16
Elena Yukie Yoshitoshi-Uebayashi, Taro Toyoda, Katsutaro Yasuda, Maki Kotaka, Keiko Nomoto, Keisuke Okita, Kentaro Yasuchika, Shinya Okamoto, Noriyuki Takubo, Toshiya Nishikubo, Tomoyoshi Soga, Shinji Uemoto, Kenji Osafune
Citrullinemia type 1 (CTLN1) is a urea cycle disorder (UCD) caused by mutations of the ASS1 gene, which is responsible for production of the enzyme argininosuccinate synthetase (ASS), and classically presented as life-threatening hyperammonemia in newborns. Therapeutic options are limited, and neurological sequelae may persist. To understand the pathophysiology and find novel treatments, induced pluripotent stem cells (iPSCs) were generated from a CTLN1 patient and differentiated into hepatocyte-like cells (HLCs)...
March 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28301398/a-pilot-study-cardiac-parameters-in-children-receiving-new-generation-antidepressants
#17
Mai Uchida, Andrea E Spencer, Tara Kenworthy, James Chan, Maura Fitzgerald, Ana Maria Rosales, Elana Kagan, Alexandra Saunders, Joseph Biederman
OBJECTIVE: Because of concerns about potential associations between high doses of citalopram and QTc prolongation in adults, this study examined whether such associations are operant in children. We hypothesized that therapeutic doses of nontricyclic antidepressant medications (non-TCAs) prescribed to children would be cardiovascularly safe. STUDY DESIGN: The sample consisted of 49 psychiatrically referred children and adolescents 6 to 17 years old of both sexes treated with a non-TCA (citalopram, escitalopram, fluoxetine, paroxetine, sertraline, bupropion, duloxetine, venlafaxine, mirtazapine)...
March 15, 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28299860/poly-3-hydroxybutyrate-fuels-the-tricarboxylic-acid-cycle-and-de-novo-lipid-biosynthesis-during-bacillus-anthracis-sporulation
#18
Marat R Sadykov, Jong-Sam Ahn, Todd J Widhelm, Valerie M Eckrich, Jennifer L Endres, Adam Driks, Gregory E Rutkowski, Kevin L Wingerd, Kenneth W Bayles
Numerous bacteria accumulate poly(3-hydroxybutyrate) (PHB) as an intracellular reservoir of carbon and energy in response to imbalanced nutritional conditions. In Bacillus spp., where PHB biosynthesis precedes the formation of the dormant cell type called the spore (sporulation), the direct link between PHB accumulation and efficiency of sporulation was observed in multiple studies. Although the idea of PHB as an intracellular carbon and energy source fueling sporulation was proposed several decades ago, the mechanisms underlying PHB contribution to sporulation have not been defined...
March 16, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28295163/cyanobacterial-carbon-metabolism-fluxome-plasticity-and-oxygen-dependence
#19
Ni Wan, Drew M DeLorenzo, Lian He, Le You, Cheryl M Immethun, George Wang, Edward E K Baidoo, Whitney Hollinshead, Jay D Keasling, Tae Seok Moon, Yinjie J Tang
Synechocystis sp. strain PCC 6803 has been widely used as a photo-biorefinery chassis. Based on its genome annotation, this species contains a complete TCA cycle, an Embden-Meyerhof-Parnas pathway (EMPP), an oxidative pentose phosphate pathway (OPPP), and an Entner-Doudoroff pathway (EDP). To evaluate how Synechocystis 6803 catabolizes glucose under heterotrophic conditions, we performed (13) C metabolic flux analysis, metabolite pool size analysis, gene knockouts, and heterologous expressions. The results revealed a cyclic mode of flux through the OPPP...
March 14, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28294044/ca2-binding-and-conformational-switch-of-the-photoprotein-mnemiopsin
#20
Shima Tarahomi, Reza H Sajedi, Hossein Rahmani, Bijan Ranjbar, Majid Taghdir
Bioluminescence in Ca2+-binding photoproteins is an intramolecular reaction triggered by the addition of Ca2+. A comparative study has been done on Ca2+-depleted and Ca2+-loaded apo-mnemiopsin to understand the structural transition of the photoprotein by Ca2+ binding. Ca2+ is removed by TCA (trichloroacetic acid) precipitation to obtain Ca2+-depleted apo-mnemiopsin. UV-visible, CD and fluorescence spectroscopic studies demonstrate that the addition of Ca2+ is brought about by the overall structure of apo-mnemiopsin becomes more open in a concentration-dependent manner without significantly influencing the secondary structure and indicate that the Ca2+-depleted form of apo-mnemiopsin, in contrast to most other EF-hand calcium binding proteins, adopt a closed conformation when compared to the Ca2+-loaded form...
March 10, 2017: Protein and Peptide Letters
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