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41.
42.
Normalizing Glutamine Concentration Causes Mitochondrial Uncoupling in an In Vitro Model of Human Skeletal Muscle
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Adela Krajcova MD Jakub Ziak Katerina Jiroutkova MD Jana Patkova Moustafa Elkalaf MD Valer Dzupa MD PhD Jan Trnka MD PhD Frantisek Duska MD PhD 《JPEN. Journal of parenteral and enteral nutrition》2015,39(2):180-189
Background: Glutamine has been considered essential for rapidly dividing cells, but its effect on mitochondrial function is unknown. Materials and Methods: Human myoblasts were isolated from skeletal muscle biopsy samples (n = 9) and exposed for 20 days to 6 different glutamine concentrations (0, 100, 200, 300, 500, and 5000 µM). Cells were trypsinized and manually counted every 5 days. Seven days before the end of exposure, half of these cells were allowed to differentiate to myotubes. Afterward, energy metabolism in both myotubes and myoblasts was assessed by extracellular flux analysis (Seahorse Biosciences, Billerica, MA). The protocol for myoblasts was optimized in preliminary experiments. To account for different mitochondrial density or cell count, data were normalized to citrate synthase activity. Results: Fastest myoblast proliferation was observed at 300 µM glutamine, with a significant reduction at 0 and 100 µM. Glutamine did not influence basal oxygen consumption, anaerobic glycolysis or respiratory chain capacity. Glutamine significantly (P = .015) influenced the leak through the inner mitochondrial membrane. Efficiency of respiratory chain was highest at 200–300 µM glutamine (~90% of oxygen used for adenosine triphosphate synthesis). Increased glutamine concentration to 500 or 5000 µM caused mitochondrial uncoupling in myoblasts and myotubes, decreasing the efficiency of the respiratory chain to ~70%. Conclusion: Glutamine concentrations, consistent with moderate clinical hypoglutaminemia (300 µM), bring about an optimal condition of myoblast proliferation and for efficiency of aerobic phosphorylation in an in vitro model of human skeletal muscle. These data support the hypothesis of hypoglutaminemia as an adaptive phenomenon in conditions leading to bioenergetic failure (eg, critical illness). 相似文献
43.
Soo Khai Ng MBBS John PM Wood DPhil Glyn Chidlow DPhil Guoge Han MBBS Thaksaon Kittipassorn MD Daniel J Peet PhD Robert J Casson DPhil FRANZCO 《Clinical & experimental ophthalmology》2015,43(4):367-376
The retina, like many cancers, produces energy from glycolysis even in the presence of oxygen. This phenomenon is known as aerobic glycolysis and eponymously as the Warburg effect. In recent years, the Warburg effect has become an explosive area of study within the cancer research community. The expanding knowledge about the molecular mechanisms underpinning the Warburg effect in cancer promises to provide a greater understanding of mammalian retinal metabolism and has motivated cancer researchers to target the Warburg effect as a novel treatment strategy for cancer. However, if the molecular mechanisms underlying the Warburg effect are shared by the retina and cancer, treatments targeting the Warburg effect may have serious adverse effects on retinal metabolism. Herein, we provide an updated understanding of the Warburg effect in mammalian retina. 相似文献
44.
The effects of chronic exercise training and diet modification on serum lipids and lipoproteins were measured in 17 hypertensive males and 41 normotensive males with documented coronary artery disease (CAD). Exercise consisted of aerobic activities which were performed at approximately 75-85% of the symptom-limited maximum heart rate for 30-40 minutes, three times weekly for 3 months. Each participant's diet was also controlled, the recommended daily intake of fat and cholesterol was no more than 40 g/day and 200 mg/day, respectively. Significant increases in estimated VO2max and total cholesterol/high density lipoprotein (HDL) and a significant decrease in serum triglycerides were documented after training. Significant differences in serum cholesterol and triglycerides between the nondiuretic and diuretic patients were also noted. No significant changes were found in low density lipoprotein (LDL), HDL, or body weight. Vigorous aerobic training and diet modification can favorably modify the deleterious effects of diuretic medications on serum triglycerides and total cholesterol/HDL in patients with documented CAD. 相似文献
45.
Summary There are important differences between the short- and long-term effects of adrenaline on determinants of glucose tolerance.
To assess this metabolic adaptation at tissue level, the present study examined the effect of acute and prolonged in vivo
elevation of adrenaline on glycogen metabolism and glycolysis in skeletal muscle. Adrenaline (50 ng · kg−1 · min−1) was infused for 2 h or 74 h and the results compared with 1 h 0.9% NaCl infusion in six trained dogs. Muscle glycogen content
was reduced by long-term adrenaline (161 ± 17 vs NaCl 250 ± 24 μmol/g dry weight;p < 0.05) but not short-term adrenaline (233 ± 21) indicating a sustained effect of adrenaline on glycogen metabolism. Acutely,
glycogen synthase I was reduced (short-term adrenaline 12 ± 6 vs NaC122 ± 7μmol glycosyl units · g−1 · min−1;p < 0.05) but returned to normal with prolonged adrenaline infusion (20 ± 5). In contrast, Km for glycogen phosphorylasea was not changed acutely (short-term adrenaline 31 ± 6 vs NaCl 27 ± 7 mmol/1 inorganic phosphate) but was reduced during long-term
infusion (19 ± 4;p < 0.05 vs short-term adrenaline). Thus, with short- and long-term adrenaline infusion, there were different enzyme changes,
although likely to promote glycogenolysis in both cases. In the glycolytic pathway the substrates glucose 6-phosphate and
fructose 6-phosphate did not change significantly and hexokinase was not inhibited. Acutely, phosphofructokinase had reduced
Vmax (short-term adrenaline 34 ± 6 vs NaCl 44 ± 5 U/g; p < 0.05) but was still above the maximal operating rate in vivo. With
prolonged adrenaline infusion, the Km for phosphofructokinase was reduced (long-term adrenaline 0.32 ± 0.03 vs NaCl 0.44 ± 0.07 mmol/l fructose 6-phosphate;p < 0.05). In this situation of relatively low glycolytic flux, the sustained glycogenolytic effect of prolonged adrenaline
infusion mediated by increased glycogen phosphorylase a ctivity occurs without a significant accumulation of hexose monophosphates
or impairment of glycolysis. 相似文献
46.
Metabolic Abnormalities in the Diabetic Heart 总被引:5,自引:0,他引:5
Lopaschuk GD 《Heart failure reviews》2002,7(2):149-159
Congestive heart failure is a major health problem in the diabetic. Diabetics have a high incidence of heart disease, including an increased incidence and severity of congestive heart failure than the non-diabetic. Progression to heart failure after an acute myocardial infarction is also more frequent in diabetics then non-diabetics. While atherosclerosis and ischemic injury are important contributing factors to this high in incidence of heart failure, another important factor is diabetes-induced changes within the heart itself. A prominent change that occurs in the diabetic is a switch in cardiac energy metabolism. Increases in fatty acid oxidation accompanied by decreases in glucose metabolism can result in the myocardium becoming almost entirely reliant on fatty acid oxidation as a source of energy. This switch in energy metabolism contributes to congestive heart failure by increasing the severity of injury following an acute myocardial infarction, and by having direct negative effects on contractile function. This paper will review the evidence linking alterations in energy metabolism to alterations in contractile function in the diabetic. 相似文献
47.
This work was designed to test whether phosphofructokinase is a target for emetine action on the heart. The effects of 37,
μM emetine on the activities of phosphofructokinase and hexokinase were measured in homogenates from perfused hearts. The action
of increasing concentrations of emetine was determined in nonperfused heart homogenates. The effect of 37 μM emetine or control solutions on the concentration of fructose-6-phosphate and fructose-1,6-phosphate was measured. The effect
of 37 μM emetine or control perfusion on the utilization of fructose-6-phosphate by phosphofructokinase in centrifugation supernatants
of homogenates and in reconstituted 27,000g pellets was measured. Double-reciprocal plots of fructose-6-phosphate concentrations
vs phosphofructokinase activities were plotted. Emetine decreased phosphofructokinase activity in homogenates from both perfused
and nonperfused hearts. Emetine did not inhibit cardiac hexokinase activity. In homogenates from nonperfused hearts, the maximal
inhibition with high concentrations of emetine was approx 50%. Emetine perfusion caused a simultaneous increase in the phosphofructokinase
substrate fructose-6-phosphate and a decrease in the phosphofructokinase product fructose-1,6-bisphosphate. Phosphofructokinase
and, consequently, glycolytic flux appear to be subcellular targets for emetine in the heart. Homogenate centrifugation studies
indicate that emetine acts on bound rather than unbound phosphofructokinase. The inhibition may be uncompetitive in nature. 相似文献
48.
《Journal of neurogenetics》2013,27(3-4):317-327
We describe the characterization of m4, an autosomal recessive, temperature-sensitive paralytic mutant in Drosophila that is associated with shortened lifespan and neurodegeneration. Deletion mapping places the mutation in the gene encoding the glycolytic enzyme, Aldolase. The mutant enzyme contains a single amino acid substitution, which results in decreased steady-state levels of Aldolase with a consequent reduction in adenosine triphosphate (ATP) levels. Transgenic-rescue experiments with a genomic construct containing the entire Aldolase gene confirm that paralysis, reduced lifespan, and neurodegeneration all result from the same mutation. Tissue-specific rescue and RNA interference (RNAi) knockdown experiments indicate that Aldolase function (and presumably glycolysis) is important both in neurons and in glia for normal lifespan and neuronal maintenance over time. Impaired glycolysis in neurons can apparently be rescued in part by glycolytically active glia. However, this rescue may depend on the exact physiological state of the neurons and may also vary in different subsets of neurons. Further studies of m4 and related mutants in Drosophila should help elucidate the connections between energy production and utilization in glia and neurons and lead to better understanding of how metabolic defects impair neuronal function and maintenance. 相似文献
49.
Stephen Yiu Chuen Choi Colin C Collins Peter W Gout Yuzhuo Wang 《The Journal of pathology》2013,230(4):350-355
The common preference of cancers for lactic acid‐generating metabolic energy pathways has led to proposals that their reprogrammed metabolism confers growth advantages such as decreased susceptibility to hypoxic stress. Recent observations, however, suggest that it generates a novel way for cancer survival. There is increasing evidence that cancers can escape immune destruction by suppressing the anti‐cancer immune response through maintaining a relatively low pH in their micro‐environment. Tumours achieve this by regulating lactic acid secretion via modification of glucose/glutamine metabolisms. We propose that the maintenance by cancers of a relatively low pH in their micro‐environment, via regulation of their lactic acid secretion through selective modification of their energy metabolism, is another major mechanism by which cancers can suppress the anti‐cancer immune response. Cancer‐generated lactic acid could thus be viewed as a critical, immunosuppressive metabolite in the tumour micro-environment rather than a ‘waste product’. This paradigm shift can have major impact on therapeutic strategy development. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
50.
Yi-Ju Hsu Mon-Chien Lee Chi-Chang Huang Chun-Sheng Ho 《International journal of medical sciences》2021,18(3):695
Gradual weight gain in modern people and a lowering onset age of metabolic disease are highly correlated with the intake of sugary drinks and sweets. Long-term excessive fructose consumption can lead to hyperglycemia, hyperlipidemia and accumulation of visceral fat. Abdominal obesity is more severe in females than in males. In this study, we used a high-fructose-diet-induced model of obesity in female mice. We investigated the effects of aquatic exercise training on body weight and body composition. After 1 week of acclimatization, female ICR mice were randomly divided into two groups: a normal group (n=8) fed standard diet (control), and a high-fructose diet (HFD) group (n=24) fed a HFD. After 4 weeks of induction followed by 4 weeks of aquatic exercise training, the 24 obese mice were divided into 3 groups (n=8 per group): HFD with sedentary control (HFD), HFD with aquatic strength exercise training (HFD+SE), and HFD with aquatic aerobic exercise training (HFD+AE). We conducted serum biochemical profile analysis, weighed the white adipose tissue, and performed organ histopathology. After 4 weeks of induction and 4 weeks of aquatic exercise training, there was no significant difference in body weight among the HFD, HFD+SE and HFD+AE groups. Serum triglyceride (TG), AST, ALT, and uric acid level were significantly lower in the HFD+SE and HFD+AE groups than in the HFD group. The weight of the perirenal fat pad was significantly lower in the HFD+AE group than in the HFD group. Hepatic TG and total cholesterol (TC) were significantly lower in the HFD+AE group than in the other groups. Long-term intake of a high-fructose diet can lead to obesity and increase the risk of metabolic disease. Based on our findings, we speculate that aquatic exercise training can effectively promote health and fitness. However, aquatic aerobic exercise training appears to have greater benefits than aquatic strength exercise training. 相似文献