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https://www.readbyqxmd.com/read/29240830/a-low-fat-diet-ameliorates-pathology-but-retains-beneficial-effects-associated-with-cpt1b-knockout-in-skeletal-muscle
#1
Jaycob D Warfel, Bolormaa Vandanmagsar, Shawna E Wicks, Jingying Zhang, Robert C Noland, Randall L Mynatt
Inhibiting fatty acid oxidation is one approach to lowering glucose levels in diabetes. Skeletal muscle specific Carnitine Palmitoyltransferase 1b knockout mice (Cpt1bm-/-) comprise a model of impaired fat oxidation; and have decreased fat mass and enhanced glucose disposal and muscle oxidative capacity compared to controls. However, unfavorable effects occur relative to controls when Cpt1bm-/- mice are fed a 25% fat diet, including decreased activity and fat free mass and increased intramuscular lipid and serum myoglobin...
2017: PloS One
https://www.readbyqxmd.com/read/29236987/extra-gonadal-actions-of-fsh-a-critical-need-for-novel-genetic-models
#2
T Rajendra Kumar
Follicle-stimulating hormone (FSH) is critical for ovarian folliculogenesis and essential for female fertility. FSH binds to FSH receptors (FSHRs) and regulates estrogen production in ovarian granulosa cells to orchestrate female reproductive physiology. Ovarian senescence that occurs as a function of aging results in loss of estrogen production and this is believed to be the major reason for bone loss in postmenopausal women. Although conflicting, studies in rodents and humans during the last decade provide genetic, pharmacological and physiological evidence that elevated FSH levels that occur in the face of normal or declining estrogen levels directly regulate bone mass and adiposity...
December 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/29234155/analysis-of-neuronal-phosphoproteome-reveals-pink1-regulation-of-bad-function-and-cell-death
#3
Huida Wan, Bin Tang, Xun Liao, Qiufang Zeng, Zhuohua Zhang, Lujian Liao
PINK1 mutations that disrupt its kinase activity cause autosomal recessive early onset Parkinson's disease (PD). Although research in recent years has elucidated a PINK1-Parkin pathway of mitophagy activation that requires PINK1 kinase activity, mitophagy-independent functions of PINK1 and their possible roles in PD pathogenesis have been proposed. Using an unbiased quantitative mass spectrometry approach to analyze the phosphoproteome in primary neurons from wild type and Pink1 knockout mice after mitochondrial depolarization, we uncovered PINK1-regulated phosphorylation sites, which involve coordinated activation of multiple signaling pathways that control cellular response to stress...
December 12, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29232263/can-the-critically-ill-patient-generate-sufficient-energy-to-facilitate-exercise-in-the-icu
#4
Danielle E Bear, Selina M Parry, Zudin A Puthucheary
PURPOSE OF REVIEW: Trials of physical rehabilitation post critical illness have yet to deliver improved health-related quality of life in critical illness survivors. Muscle mass and strength are lost rapidly in critical illness and a proportion of patients continue to do so resulting in increased mortality and functional disability. Addressing this issue is therefore fundamental for recovery from critical illness. RECENT FINDINGS: Altered mitochondrial function occurs in the critically ill and is likely to result in decreased adenosine tri-phosphate (ATP) production...
December 9, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/29229602/vegfr-2-mediated-reprogramming-of-mitochondrial-metabolism-regulates-the-sensitivity-of-acute-myeloid-leukemia-to-chemotherapy
#5
Sandrina Nóbrega-Pereira, Francisco Caiado, Tânia Carvalho, Inês Matias, Gonçalo Graça, Luís Gafeira Gonçalves, Bruno Silva-Santos, Haakan Norell, Sérgio Dias
Metabolic reprogramming is central to tumorigenesis, but whether chemotherapy induces metabolic features promoting recurrence remains unknown. We established a mouse xenograft model of human acute myeloid leukemia (AML) that enabled chemotherapy-induced regressions of established disease followed by lethal regrowth of more aggressive tumor cells. Human AML cells from terminally ill mice treated with chemotherapy (chemoAML) had higher lipid content, increased lactate production and ATP levels, reduced expression of PPARG coactivator 1α (PGC-1α), and fewer mitochondria than controls from untreated AML animals...
December 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/29228856/uncovering-the-proteome-response-of-murine-neuroblastoma-cells-against-low-dose-exposure-to-saxitoxin
#6
Xiao Chen, Ye Sun, Haiyan Huang, Wei Liu, Panpan Hu, Xinfeng Huang, Fei Zou, Jianjun Liu
The potent neurotoxin saxitoxin produced by both marine and freshwater phytoplankton causes paralytic shellfish poisoning syndrome. The toxicity and mode of action of the acute exposure of high-dose saxitoxin have been intensively studied for decades; however, the potential risk of exposure of low-dose saxitoxin remained to be uncovered. Here we present a proteomics study of murine neuroblastoma N2A cell with low-dose saxitoxin exposure (1 nM and 10 nM, 24-h intoxication). Differential proteins were profiled by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS)...
December 11, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/29228768/recovery-of-mrs3%C3%AE-mrs4%C3%AE-saccharomyces-cerevisiae-cells-under-iron-sufficient-conditions-and-the-role-of-fe580
#7
Michael J Moore, Joshua Wofford, Andrew Dancis, Paul Alan Lindahl
Mrs3 and Mrs4 are mitochondrial inner membrane proteins that deliver an unidentified cytosolic iron species into the matrix for use in iron-sulfur-cluster (ISC) and heme biosynthesis. The Mrs3/4 double-deletion strain (ΔΔ) grew slowly in iron-deficient glycerol/ethanol medium but recovered to WT rates in iron-sufficient medium. ΔΔ cells grown under both iron-deficient and iron-sufficient respiring conditions accumulated large amounts of iron relative to WT cells, indicating iron homeostatic dysregulation regardless of nutrient iron status...
December 11, 2017: Biochemistry
https://www.readbyqxmd.com/read/29224095/sex-differences-in-muscle-wasting
#8
Lindsey J Anderson, Haiming Liu, Jose M Garcia
With aging and other muscle wasting diseases, men and women undergo similar pathological changes in skeletal muscle: increased inflammation, enhanced oxidative stress, mitochondrial dysfunction, satellite cell senescence, elevated apoptosis and proteasome activity, and suppressed protein synthesis and myocyte regeneration. Decreased food intake and physical activity also indirectly contribute to muscle wasting. Sex hormones also play important roles in maintaining skeletal muscle homeostasis. Testosterone is a potent anabolic factor promoting muscle protein synthesis and muscular regeneration...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29222404/lack-of-parkin-anticipates-the-phenotype-and-affects-mitochondrial-morphology-and-mtdna-levels-in-a-mouse-model-of-parkinson-s-disease
#9
Milena Pinto, Nadee Nissanka, Carlos T Moraes
PARK2 is the most common gene mutated in monogenic recessive familial cases of Parkinson's disease (PD). Pathogenic mutations cause a loss of function of the encoded protein Parkin. ParkinKO mice, however, poorly represent human PD symptoms as they only exhibit mild motor phenotypes, minor dopamine metabolism abnormalities, and no signs of dopaminergic neurodegeneration. Parkin has been shown to participate in mitochondrial turnover, by targeting damaged mitochondria, with low membrane potential, to mitophagy...
December 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29222160/the-interactome-of-intact-mitochondria-by-cross-linking-mass-spectrometry-provides-evidence-for-co-existing-respiratory-supercomplexes
#10
Fan Liu, Philip Lössl, Beverley M Rabbitts, Robert S Balaban, Albert J R Heck
Mitochondria exert an immense amount of cytophysiological functions, but the structural basis of most of these processes is still poorly understood. Here we use cross-linking mass spectrometry to probe the organization of proteins in native mouse heart mitochondria. Our approach provides the largest survey of mitochondrial protein interactions reported so far. In total, we identify 3,322 unique residue-to-residue contacts involving half of the mitochondrial proteome detected by bottom-up proteomics. The obtained mitochondrial protein interactome gives insights in the architecture of defined protein assemblies, the sub-mitochondrial localization, and the mitochondrial localization of five proteins not yet included in the MitoCarta database...
December 8, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29222138/application-of-large-scale-aptamer-based-proteomic-profiling-to-planned-myocardial-infarctions
#11
Jaison Jacob, Debby Ngo, Nancy Finkel, Rebecca Pitts, Scott Gleim, Mark D Benson, Michelle J Keyes, Laurie A Farrell, Thomas Morgan, Lori L Jennings, Robert Gerszten
Background -Emerging proteomic technologies using novel affinity-based reagents allow for efficient multiplexing with high sample throughput. To identify early biomarkers of myocardial injury, we recently applied an aptamer-based proteomic profiling platform that measures 1,129 proteins to samples from patients undergoing septal alcohol ablation for hypertrophic cardiomyopathy, a human model of "planned myocardial injury" (PMI). Here we examined the scalability of this approach using a markedly expanded platform to study a far broader range of human proteins in the context of myocardial injury...
December 8, 2017: Circulation
https://www.readbyqxmd.com/read/29221988/modulations-of-keap1-nrf2-signaling-axis-by-tiia-ameliorated-the-oxidative-stress-induced-myocardial-apoptosis
#12
Shi-Hai Yan, Ning-Wei Zhao, Zhi-Rong Geng, Jia-Yin Shen, Fu-Ming Liu, Dong Yan, Jie Zhou, Chao Nie, Cheng-Cai Huang, Zhu-Yuan Fang
Mounting evidence has strongly implicated oxidative stress in the development of cardiac dysfunction, and myocardial apoptosis contributes to the pathogenesis of heart failure. Quantitative cardiac proteomics data revealed that pressure load by TAC resulted in a significant decline in mitochondrial metabolic activity, where TIIA (Tanshinone IIA sulfonate) treatment reversed it in vivo, which might be mediated by Nrf2. In NRVMs, TIIA treatment ameliorated H2O2-induced caspase-3/9 activations through the suppression of p38 and mTOR signaling pathways, where caspase-mediated cleavage of YY1 and PARP resulted in the defects in mitochondrial biogenesis and DNA repair, and this event finally led to cardiomyocyte apoptosis...
December 5, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29220206/aerobic-training-but-no-resistance-training-increases-sirt3-in-skeletal-muscle-of-sedentary-obese-male-adolescents
#13
Katya Vargas-Ortiz, Victoriano Pérez-Vázquez, Arturo Figueroa, Francisco J Díaz, Paulina G Montaño-Ascencio, Maciste H Macías-Cervantes
In recent years, prevalence of obesity in children and adolescents has increased. A strategy for prevention and management of obesity is aerobic training (AT) due to its effectiveness to decrease fat mass. AT increases the content of SIRT3, a mitochondrial protein that increases the expression of PGC-1α and NFR1, thereby enhances mitochondrial function and metabolic health. Resistance training (RT) provides metabolic benefits but its effect on SIRT3 content is unknown. To compare the effect of AT and RT on SIRT3, PGC-1α and NRF-1 protein levels in skeletal muscle of sedentary obese adolescents...
December 8, 2017: European Journal of Sport Science
https://www.readbyqxmd.com/read/29219221/improved-developmental-competence-in-embryos-treated-with-lycopene-during-in-vitro-culture
#14
M M R Chowdhury, Ayman Mesalam, Imran Khan, Myeong-Don Joo, Kyeong-Lim Lee, Lianguang Xu, Fahmida Afrin, Il-Keun Kong
In vitro embryo development remains suboptimal compared to in vivo development due to the challenge from various stressors associated with in vitro culturing of oocytes. When 0.2 μM lycopene was added to oocyte in vitro maturation and embryo culture media, to assess its antioxidant effects on embryo development, we observed a significant (p<0.05) increase in cleavage and blastocyst development rates compared to the corresponding controls (84.3 ± 0.6% vs. 73.1 ± 1.9% and 41.0 ± 1.4% vs. 33.4 ± 0.7%, respectively)...
December 8, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/29219180/laminar-shear-stress-promotes-mitochondrial-homeostasis-in-endothelial-cells
#15
Li-Hong Wu, Hao-Chun Chang, Pei-Ching Ting, Danny Ling Wang
Vascular endothelial cells (ECs) are constantly subjected to flow-induced shear stress that is crucial for endothelial functions. Laminar shear stress (LSS) exerts atheroprotection to ECs. Mitochondrial homeostasis is essential for cellular survival. However, the effects of LSS on mitochondrial homeostasis in ECs remain unclear. Mitochondrial homeostasis in ECs exposed to LSS was examined. Cultured human umbilical vein ECs were subjected to LSS (12 dynes/cm2 ) generated by a parallel-plate flow chamber system...
December 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29216582/cellular-and-mitochondrial-determination-of-low-molecular-mass-organic-acids-by-lc-ms-ms
#16
Jessica Fiori, Elisa Amadesi, Flaminia Fanelli, Concetta Valentina Tropeano, Michela Rugolo, Roberto Gotti
A selective and sensitive method for the determination of low molecular mass organic acids (LMMOAs) in cell and mitochondrial extracts is presented. The analytical method consists in the separation by reversed phase liquid chromatography and detection with tandem mass spectrometry (LC-MS/MS) of the LMMOAs like malic, succinic, formic and citric acids. These acids are among the cellular intermediates of the tricarboxylic acid cycle (TCA), thus their quantitation can provide essential information about the catabolic and anabolic processes occurring in cells under physiological and pathological conditions...
November 29, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29215172/fibroblast-growth-factor-21-increases-hepatic-oxidative-capacity-but-not-physical-activity-or-energy-expenditure-in-hepatic-pgc-1%C3%AE-deficient-mice
#17
Justin A Fletcher, Melissa A Linden, Ryan D Sheldon, Grace M Meers, E Matthew Morris, Anthony Butterfield, James W Perfield, R Scott Rector, John P Thyfault
Fibroblast growth factor 21 (FGF21) treatment drives metabolic improvements, including increased metabolic flux and reduced hepatic steatosis, but mechanisms responsible for these effects remain to be fully elucidated. We tested if a targeted reduction in hepatic PGC-1α, which has been shown to occur with obesity, negatively impacted the metabolic effects of FGF21. We infused FGF21 (1 mg kg-1  day-1 ) or saline in chow-fed wild-type (WT) and liver-specific PGC-1α +/- (LPGC-1α) mice for 4 weeks. FGF21 administration lowered serum insulin and cholesterol (P ≤ 0...
December 7, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/29215066/pharmacological-inhibition-of-rev-erb-stimulates-differentiation-inhibits-turnover-and-reduces-fibrosis-in-dystrophic-muscle
#18
Ryan D Welch, Cyrielle Billon, Aurore-Cecile Valfort, Thomas P Burris, Colin A Flaveny
Duchenne muscular dystrophy (DMD) is a debilitating X-linked disorder that is fatal. DMD patients lack the expression of the structural protein dystrophin caused by mutations within the DMD gene. The absence of functional dystrophin protein results in excessive damage from normal muscle use due to the compromised structural integrity of the dystrophin associated glycoprotein complex. As a result, DMD patients exhibit ongoing cycles of muscle destruction and regeneration that promote inflammation, fibrosis, mitochondrial dysfunction, satellite cell (SC) exhaustion and loss of skeletal and cardiac muscle function...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29211964/metabolic-costs-of-exposure-to-wastewater-effluent-lead-to-compensatory-adjustments-in-respiratory-physiology-in-bluegill-sunfish
#19
Sherry Du, Erin S McCallum, Maryam Vaseghi-Shanjani, Jasmine A Choi, Theresa R Warriner, Sigal Balshine, Graham R Scott
Municipal wastewater effluent is a major source of aquatic pollution and has potential to impact cellular energy metabolism. However, it is poorly understood whether wastewater exposure impacts whole-animal metabolism and whether this can be accommodated with adjustments in respiratory physiology. We caged bluegill sunfish (Lepomis macrochirus) for 21 days at two sites downstream (either 50 m or 830 m) from a wastewater treatment plant (WWTP). Survival was reduced in fish caged at both downstream sites compared to an uncontaminated reference site...
December 6, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29211784/urinary-metabolomic-analysis-to-identify-preterm-neonates-exposed-to-histological-chorioamnionitis-a-pilot-study
#20
Claudia Fattuoni, Carlo Pietrasanta, Lorenza Pugni, Andrea Ronchi, Francesco Palmas, Luigi Barberini, Angelica Dessì, Roberta Pintus, Vassilios Fanos, Antonio Noto, Fabio Mosca
OBJECTIVE: Chorioamnionitis is a leading cause of preterm birth worldwide, with higher incidence at lower gestational ages. An early and reliable diagnosis of histological chorioamnionitis (HCA) in preterm infants may be helpful in guiding postnatal management, especially the administration of prophylactic antibiotics to prevent early-onset sepsis. The main aim of this study was to investigate metabolomic analysis of urines collected in the first 24 hours of life as diagnostic tool of HCA...
2017: PloS One
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