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Hailong Li, Zhongyuan Tang, Peng Chu, Yanlin Song, Ying Yang, Bin Sun, Mengyue Niu, Eskandar Qaed, Abdullah Shopit, Guozhu Han, Xiaodong Ma, Jinyong Peng, Min Hu, Zeyao Tang
Methylglyoxal (MGO), an active metabolite of glucose, is observed in high levels in the tissues and blood of diabetic patients. Phosphocreatine (PCr), a high-energy phosphate compound, exhibits a range of pharmacological actions but little is well known of its neuroprotective action. The aim of the present study was to investigate the neuroprotective effects and the possible mechanisms of PCr. Diabetes is closely associated with neurodegenerative diseases, leading not only to the peripheral nervous system (PNS) and but also to central nervous system (CNS) damage...
March 17, 2018: Free Radical Biology & Medicine
Yogi Umbarawan, Mas Rizky A A Syamsunarno, Norimichi Koitabashi, Aiko Yamaguchi, Hirofumi Hanaoka, Takako Hishiki, Yoshiko Nagahata-Naito, Hideru Obinata, Motoaki Sano, Hiroaki Sunaga, Hiroki Matsui, Yoshito Tsushima, Makoto Suematsu, Masahiko Kurabayashi, Tatsuya Iso
Aims: The metabolism of the failing heart is characterized by an increase in glucose uptake with reduced fatty acid (FA) oxidation. We previously found that the genetic deletion of fatty acid binding protein-4 and -5 (DKO) induces an increased myocardial reliance on glucose with decreased FA uptake in mice. However, whether this fuel switch confers functional benefit during the hypertrophic response remains open to debate. To address this question, we investigated the contractile function and metabolic profile of DKO hearts subjected to pressure overload...
March 15, 2018: Cardiovascular Research
Attila Kiss, Huaqing Shu, Ouafa Hamza, David Santer, Eva Verena Tretter, Shanglong Yao, Klaus Markstaller, Seth Hallström, Bruno K Podesser, Klaus Ulrich Klein
OBJECTIVES: Previous studies demonstrated that preconditioning with argon gas provided a marked reduction in inflammation and apoptosis and increased myocardial contractility in the setting of acute myocardial ischaemia-reperfusion (IR). There is substantial evidence that myocardial IR injury following cardioplegic arrest is associated with the enhancement of apoptosis and inflammation, which is considered to play a role in cardiac functional impairment. Therefore, the present study was designed to clarify whether preconditioning with argon gas enhances recovery of cardiac function following cardioplegic arrest...
March 13, 2018: European Journal of Cardio-thoracic Surgery
Raghavendra Rao, Motaz Nashawaty, Saher Fatima, Kathleen Ennis, Ivan Tkac
Hyperglycemia (blood glucose concentration >150 mg/dL) is common in extremely low gestational age newborns (ELGANs; birth at <28 week gestation). Hyperglycemia increases the risk of brain injury in the neonatal period. The long-term effects are not well understood. In adult rats, hyperglycemia alters hippocampal energy metabolism. The effects of hyperglycemia on the developing hippocampus were studied in rat pups. In Experiment 1, recurrent hyperglycemia of graded severity (moderate hyperglycemia (moderate-HG), mean blood glucose 214...
March 13, 2018: NMR in Biomedicine
Jian-Ming Hu, Huang-Tao Sun
BACKGROUND: To find potential serum biomarkers of microwave ablation (MWA) for treatment of human lung cancer by1 H nuclear magnetic resonance (NMR)-based metabolomics analysis. METHODS: Serum specimens collected from 43 healthy individuals, 39 patients with advanced non-small cell lung cancer (NSCLC) and 38 NSCLC patients treated with MWA, were subjected to1 H NMR-based metabolomics analysis. Partial least squares discriminant analysis was used to analyze the data...
March 12, 2018: Radiation Oncology
P Sedivy, M Dezortova, M Drobny, Z Vlasakova, V Herynek, M Hajek
Type I diabetes mellitus (DM1) is a complex disease with adverse effects on organs and tissues despite compensation by insulin treatment. The goal of our study was to study how kidney diseases change (31)P MR parameters of muscle metabolism in DM1 patients with respect to gender. 59 DM1 patients (19m/14f without and 13m/5f with nephropathy) and 26 (14m/12f) healthy volunteers were examined using (31)P magnetic resonance spectroscopy at 3T tomograph at rest, and during and after a calf muscle exercise. The exercise consisted of a six-minute plantar flexion using a pedal ergometer followed by a six-minute recovery...
March 12, 2018: Physiological Research
Ewelina K Wardzinski, Alina Kistenmacher, Uwe H Melchert, Kamila Jauch-Chara, Kerstin M Oltmanns
BACKGROUND: There is evidence that the brain's energy status is lowered in obesity despite of chronic hypercaloric nutrition. The underlying mechanisms are unknown. We hypothesized that the brain of obese people does not appropriately generate energy in response to a hypercaloric supply. METHODS: Glucose was intravenously infused in 17 normal weights and 13 obese participants until blood glucose concentrations reached the postprandial levels of 7 mmol/L and 10 mmol/L...
March 6, 2018: Metabolism: Clinical and Experimental
Wei Wang, Qi Wang, Wanyou Yu, Lianhua Chen, Zhong Li
PURPOSE: To observe the efficacy of phosphocreatine pre-administration (PCr-PA) on X-linked inhibitor of apoptosis protein (XIAP), the second mitochondia-derived activator of caspase (Smac) and apoptosis in the ischemic penumbra of rats with focal cerebral ischemia-reperfusion injury (CIRI). METHODS: A total of 60 healthy male Sprague Dawley (SD) rats were randomly divided into three groups (n=20): group A (the sham operation group), group B &lt;intraperitoneally injected with 20 mg/kg (10 mg/ml) of saline before preparing the ischemia-reperfusion (IR) model&gt;, and group C &lt;intraperitoneally injected with 20 mg/kg (10 mg/ml) of PCr immediately before preparing the IR model&gt;...
February 2018: Acta Cirúrgica Brasileira
Hannah J Whittington, Philip J Ostrowski, Debra J McAndrew, Fang Cao, Andrew Shaw, Thomas R Eykyn, Hannah Lake, Jack Tyler, Jurgen E Schneider, Stefan Neubauer, Sevasti Zervou, Craig A Lygate
Aims: Mitochondrial creatine kinase (MtCK) couples ATP production via oxidative phosphorylation to phosphocreatine in the cytosol, which acts as a mobile energy store available for regeneration of ATP at times of high demand. We hypothesised that elevating MtCK would be beneficial in ischaemia-reperfusion (I/R) injury. Methods and Results: Mice were created overexpressing the sarcomeric MtCK gene with αMHC promoter at the Rosa26 locus (MtCK-OE) and compared with wild-type (WT) littermates...
March 2, 2018: Cardiovascular Research
Erika M Ripley, Geoffrey D Clarke, Vala Hamidi, Robert A Martinez, Floyd D Settles, Carolina Solis, Shengwen Deng, Muhammad Abdul-Ghani, Devjit Tripathy, Ralph A DeFronzo
Mitochondrial dysfunction has been described in insulin resistant (IR) states including type 2 diabetes mellitus (T2DM). Previous studies using31 P-MRS in T2DM reported results as relative concentrations of metabolite ratios, which could obscure changes in phosphocreatine [PCr] and [ATP] and attenuate differences between T2DM and NGT individuals. We used a novel image-guided31 P-MRS method to quantitate phosphorus metabolites in vastus lateralis (VL) muscle in 11 T2DM and 14 NGT subjects. Subjects received OGTT, euglycemic insulin clamp,31 P-MRS study to measure absolute concentrations (mM) of [PCr], inorganic phosphate [Pi], and [ATP], and VL muscle biopsy to evaluate mitochondrial density...
March 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Chi-Hyeon Yoo, Kyu-Ho Song, Song-I Lim, Dong-Cheol Woo, Bo-Young Choe
Recent evidence suggests that the glutamate system plays an important role in the pathogenesis of major depressive disorder (MDD). The aim of this study was to investigate the effects of light deprivation (LD) in the prefrontal cortex (PFC) of animals with depression-like behavior, targeting the glutamate system, using in vivo proton magnetic resonance spectroscopy (1 H MRS). Male Sprague-Dawley rats were housed in constant darkness for six weeks (n = 12; LD group), while controls (n = 8) were housed under normal light cycles...
March 1, 2018: Brain Research
Joana Carrola, Ricardo J B Pinto, Maryam Nasirpour, Carmen S R Freire, Ana M Gil, Conceição Santos, Helena Oliveira, Iola F Duarte
The expansion of biomedical and therapeutic applications of silver nanoparticles (AgNPs) raises the need to further understand their biological effects on human cells. In this work, NMR metabolomics has been applied to reveal the metabolic effects of AgNPs toward human hepatoma (HepG2) cells, which are relevant with respect to nanoparticle accumulation and detoxification. Cellular responses to widely disseminated citrate-coated AgNPs (Cit30) and to emergent biogenic AgNPs prepared using an aqueous plant extract as reducing and stabilizing agent (GS30) have been compared with a view to assess the influence of nanoparticle coating on the metabolic effects produced...
March 9, 2018: Journal of Proteome Research
Christopher Thompson, Anni Vanhatalo, Stefan Kadach, Lee J Wylie, Jonathan Fulford, Scott K Ferguson, Jamie R Blackwell, Stephen J Bailey, Andrew M Jones
The physiological and exercise performance adaptations to sprint interval training (SIT) may be modified by dietary nitrate (NO3 - ) supplementation. However, it is possible that different types of NO3 - supplementation evoke divergent physiological and performance adaptations to SIT. The purpose of this study was to compare the effects of 4 weeks SIT with and without concurrent dietary NO3 - supplementation administered as either NO3 - -rich beetroot juice (BR) or potassium NO3 - (KNO3 ). Thirty recreationally-active subjects completed a battery of exercise tests before and after a 4 week intervention in which they were allocated to one of three groups: 1) SIT undertaken without dietary NO3 - supplementation (SIT); 2) SIT accompanied by concurrent BR supplementation (SIT+BR); or 3) SIT accompanied by concurrent KNO3 supplementation (SIT+KNO3 )...
March 1, 2018: Journal of Applied Physiology
J Scott Lee, Ruth X Wang, Erica E Alexeev, Jordi M Lanis, Kayla D Battista, Louise E Glover, Sean P Colgan
Intestinal epithelial cells form a selectively permeable barrier to protect colon tissues from luminal microbiota and antigens, and to mediate nutrient, fluid, and waste flux in the intestinal tract. Dysregulation of the epithelial cell barrier coincides with profound shifts in metabolic energy, especially in the colon, which exists in an energetically depleting state of physiological hypoxia. However, studies that systematically examine energy flux and adenylate metabolism during intestinal epithelial barrier development and restoration after disruption are lacking...
February 27, 2018: Journal of Biological Chemistry
Joanna L Bowtell, Magni Mohr, Jonathan Fulford, Sarah R Jackman, Georgios Ermidis, Peter Krustrup, Katya N Mileva
Background: Caffeine has been shown to enhance exercise performance and capacity. The mechanisms remain unclear but are suggested to relate to adenosine receptor antagonism, resulting in increased central motor drive, reduced perception of effort, and altered peripheral processes such as enhanced calcium handling and extracellular potassium regulation. Our aims were to investigate how caffeine (i) affects knee extensor PCr kinetics and pH during repeated sets of single-leg knee extensor exercise to task failure and (ii) modulates the interplay between central and peripheral neural processes...
2018: Frontiers in Nutrition
Uwe Schlattner, Laurence Kay, Malgorzata Tokarska-Schlattner
Isoforms of creatine kinase (CK) generate and use phosphocreatine, a concentrated and highly diffusible cellular "high energy" intermediate, for the main purpose of energy buffering and transfer in order to maintain cellular energy homeostasis. The mitochondrial CK isoform (mtCK) localizes to the mitochondrial intermembrane and cristae space, where it assembles into peripherally membrane-bound, large cuboidal homooctamers. These are part of proteolipid complexes wherein mtCK directly interacts with cardiolipin and other anionic phospholipids, as well as with the VDAC channel in the outer membrane...
2018: Sub-cellular Biochemistry
Andreas Boss, Linda Heskamp, Vincent Breukels, Lauren J Bains, Mark J van Uden, Arend Heerschap
The rate of phosphocreatine (PCr) recovery (kPCr ) after exercise, characterizing muscle oxidative capacity, is traditionally assessed with unlocalized31 P magnetic resonance spectroscopy (MRS) using a single surface coil. However, because of intramuscular variation in fibre type and oxygen supply, kPCr may be non-uniform within muscles. We tested this along the length of the tibialis anterior (TA) muscle in 10 male volunteers. For this purpose we employed a 3T MR system with a31 P/1 H volume transmit coil combined with a home-built31 P phased-array receive probe, consisting of 5 coil elements covering the TA muscle length...
February 18, 2018: Journal of Physiology
Ajay Thankamony, Graham J Kemp, Albert Koulman, Vlada Bokii, David B Savage, Chris Boesch, Leanne Hodson, David B Dunger, Alison Sleigh
Intramyocellular lipid (IMCL) is of particular metabolic interest, but despite many proton magnetic resonance spectroscopy (1H MRS) studies reporting IMCL content measured by the methylene (CH2) resonance signal, little is known about its composition. Here we validated IMCL CH3:CH2 ratio as a compositional marker using 1H MRS at short echo time, and investigated IMCL content and composition during a 28-hour fast in 24 healthy males. Increases in IMCL CH2 relative to the creatine and phosphocreatine resonance (Cr) at 3...
February 9, 2018: Scientific Reports
Fang Mingxing, Giovanni Landoni, Alberto Zangrillo, Fabrizio Monaco, Vladimir V Lomivorotov, Cao Hui, Maxim Novikov, Valery Nepomniashchikh, Evgeny Fominskiy
OBJECTIVE: There is experimental evidence that phosphocreatine (PCr) can decrease ischemia/reperfusion injury of the heart. The authors investigated if PCr would improve heart performance as compared with standard treatment in cardiac surgery. DESIGN: Meta-analysis of randomized controlled trials. SETTING: Hospitals. PARTICIPANTS: Adult and pediatric patients undergoing cardiac surgery. INTERVENTIONS: The ability of PCr to improve cardiac outcomes as compared with standard treatment was investigated...
July 24, 2017: Journal of Cardiothoracic and Vascular Anesthesia
S Jungi, X Fu, A Segiser, M Busch, P Most, M Fiedler, T Carrel, H Tevaearai Stahel, S L Longnus, Henriette Most
Gene-targeted therapy with the inotropic Ca2 + -sensor protein S100A1 rescues contractile function in post-ischemic heart failure and is being developed towards clinical trials. Its proven beneficial effect on cardiac metabolism and mitochondrial function suggests a cardioprotective effect of S100A1 in myocardial ischemia-reperfusion injury (IRI). Fivefold cardiomyocyte-specific S100A1 overexpressing, isolated rat hearts perfused in working mode were subjected to 28 min ischemia (37 °C) followed by 60 min reperfusion...
February 1, 2018: Journal of Cardiovascular Translational Research
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