Mycobacterium tuberculosis Limits Host Glycolysis and IL-1β by Restriction of PFK-M via MicroRNA-21

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PO2 and pH changes in the retina of the crab Ocypode ryderi: evidence for aerobic glycolysis

Summary The isolated retina of the terrestrial crab Ocypode ryderi exhibits a pronounced lactate production in spite of being supplied with sufficient O₂ (140 torr). To determine whether this lactate production is caused by hypoxic areas in the tissue or represents aerobic glycolysis, oxygen partial pressure and pH measurements with two-channel glass microelectrodes and additional biochemical analyses were carried out on this organ. Distinct profiles were obtained for O₂ partial pressure and pH inside the tissue. At a depth of 200 m different O₂ partial pressure levels could be observed depending on the O₂ partial pressure in the medium (85 torr at 280 torr and 36 torr at 130 torr, respectively). The extracellular pH displays a similar pattern; it reaches a stable value of 7.15 at 100 m inside the tissue. Lowering bath O₂ partial pressure from 280 torr to about 15 torr (hypoxia) induces a decrease of the O₂ partial pressure in the tissue with different time-courses for different tissue depths. However, hypoxia did not change the extracellular pH. Addition of antimycin A (100 mol · 1^-1) to the medium abolishes the O₂ partial pressure gradient and the delayed recovery of the tissue O₂ partial pressure after hypoxia. These results and the biochemical data suggest that in the crab retina a high glycolytic activity occurs simultaneously with oxydative carbohydrate degradation (aerobic glycolysis).Abbreviations AEC Atkinson energy charge - DC bioelectric potential - dw dry weight - HEPES N-[2-Hydroxyethyl]piperazine-N-[2-ethanesulphonic acid] - PCO₂ carbon dioxide partial pressure - PO₂ oxygen partial pressure - P _tO₂ oxygen partial pressure inside the tissue - P _mO₂ oxygen partial pressure in the medium - pH_t pH inside the tissue - pH_m pH in the superfusion medium     

Oncoprotein CIP2A promotes the disassembly of primary cilia and inhibits glycolytic metabolism

In most mammalian cells, the primary cilium is a microtubule‐enriched protrusion of the plasma membrane and acts as a key coordinator of signaling pathways during development and tissue homeostasis. The primary cilium is generated from the basal body, and cancerous inhibitor of protein phosphatase 2A (CIP2A), the overexpression of which stabilizes c‐MYC to support the malignant growth of tumor cells, is localized in the centrosome. Here, we show that CIP2A overexpression induces primary cilia disassembly through the activation of Aurora A kinase, and CIP2A depletion increases ciliated cells and cilia length in retinal pigment epithelium (RPE1) cells. CIP2A depletion also shifts metabolism toward the glycolytic pathway by altering the expression of metabolic genes related to glycolysis. However, glycolytic activation in CIP2A‐depleted cells does not depend on cilia assembly, even though enhanced cilia assembly alone activates glycolytic metabolism. Collectively, these data suggest that CIP2A promotes primary cilia disassembly and that CIP2A depletion induces metabolic reprogramming independent of primary cilia.     

Physiology of pyruvate metabolism in Lactococcus lactis

Lactococcus lactis, a homofermentative lactic acid bacterium, has been studied extensively over several decades to obtain sometimes conflicting concepts relating to the growth behaviour. In this review some of the data will be examined with respect to pyruvate metabolism. It will be demonstrated that the metabolic transformation of pyruvate can be predicted if the growth-limiting constraints are adequately established. In general lactate remains the major product under conditions in which sugar metabolism via a homolactic fermentation can satisfy the energy requirements necessary to assimilate anabolic substrates from the medium. In contrast, alternative pathways are involved when this energy supply becomes limiting or when the normal pathways can no longer maintain balanced carbon flux. Pyruvate occupies an important position within the metabolic network of L. lactis and the control of pyruvate distribution within the various pathways is subject to co-ordinated regulation by both gene expression mechanisms and allosteric modulation of enzyme activity.     

An Uncoupling of the Processes of Oxidation and Phosphorylation in Glycolysis

Data on alterations of the properties of glyceraldehyde-3-phosphate dehydrogenase upon oxidation of its functional groups are reviewed; a mechanism of uncoupling of oxidation and phosphorylation in glycolysis is considered. Possible ways of regulating uncoupling, and the physiological importance of this process, are discussed.     

Influence of vanadate on glycolysis,intracellular sodium,and pH in perfused rat hearts

Vanadium compounds have been shown to cause a variety of biological and metabolic effects including inhibition of certain enzymes, alteration of contractile function, and as an insulin like regulator of glucose metabolism. However, the influence of vanadium on metabolic and ionic changes in hearts remains to be understood. In this study we have examined the influence of vanadate on glucose metabolism and sodium transport in isolated perfused rat hearts. Hearts were perfused with 10 mM glucose and varying vanadate concentrations (0.7100 M) while changes in high energy phosphates (ATP and phosphocreatine (PCr)), intracellular pH, and intracellular sodium were monitored using 31P and 23Na NMR spectroscopy. Tissue lactate, glycogen, and (Na+, K+)-ATPase activity were also measured using biochemical assays. Under baseline conditions, vanadate increased tissue glycogen levels two fold and reduced (Na+, K+)-ATPase activity. Significant decreases in ATP and PCr were observed in the presence of vanadate, with little change in intracellular pH. These changes under baseline conditions were less severe when the hearts were perfused with glucose, palmitate and b-hydroxybutyrate. During ischemia vanadate did not limit the rise in intracellular sodium, but slowed sodium recovery on reperfusion. The presence of vanadate during ischemia resulted in attenuation of acidosis, and reduced lactate accumulation. Reperfusion in the presence of vanadate resulted in a slower ATP recovery, while intracellular pH and PCr recovery was not affected. These results indicate that vanadate alters glucose utilization and (Na+, K+)-ATPase activity and thereby influences the response of the myocardium to an ischemic insult.     

Fructose-1,6-bisphosphate as a metabolic substrate in hog ileum smooth muscle during hypoxial

Exogenously applied fructose-1,6-bisphosphate has been reported to be effective in preventing some damage to the small intestine during ischemia. To determine whether exogenously applied fructose-1,6-bisphosphate protects ileum smooth muscle from damage from hypoxia and from reoxygenation, we examined the effect of fructose-1,6-bisphosphate on the ability of hog ileum smooth muscle to maintain isometric force during hypoxia and to generate isometric force after reoxygenation in the presence of 5 mM glucose. After 180 min of hypoxia, tissues incubated with 20 mM fructose-1,6-bisphosphate maintained significantly greater levels of isometric force than tissues incubated in the absence of exogenous substrate (23% of pre-hypoxia force compared to 16%). During the first contraction following reoxygenation there was a significantly greater force generation in tissues incubated with 20 mM fructose-1,6-bisphosphate during the hypoxia period compared to tissues with no exogenous substrate included during the hypoxia period (29% of pre-hypoxia force compared to 19%). However, glucose always was a better metabolic substrate compared to fructose-1,6-bisphosphate under all experimental conditions. The presence of fructose-1,6-bisphosphate during hypoxia likely improved tissue function by fructose-1,6-bisphosphate entering the cells and acting as a glycolytic intermediate, since during a 120 min period of hypoxia, unmounted ileum smooth muscle metabolized 1,6-¹³C-fructose-1,6-bisphosphate to 3-¹³C-lactate. This conversion of 1,6-¹³C-fructose-1,6-bisphosphate to 3-¹³C-lactate was inhibited by the addition of 1 mM iodoacetic acid, a glycolytic inhibitor. We conclude that exogenously provided fructose-1,6-bisphosphate does provide modest protection of ileum smooth muscle from hypoxic damage by functioning as a glycolytic intermediate and improving the cellular energy state.This work was supported in part by NIH (HL48783 to CDH), NSF (Instrumentation Grant 8908304), and the Department of Physiology of the University of Missouri. T. Juergens was supported by the School of Medicine and the Department of Physiology of the University of Missouri.