Host cell glutamine metabolism as a potential antiviral target

A virus minimally contains a nucleic acid genome packaged by a protein coat. The genome and capsid together are known as the nucleocapsid, which has an envelope containing a lipid bilayer (mainly phospholipids) originating from host cell membranes. The viral envelope has transmembrane proteins that are usually glycoproteins. The proteins in the envelope bind to host cell receptors, promoting membrane fusion and viral entry into the cell. Virus-infected host cells exhibit marked increases in glutamine utilization and metabolism. Glutamine metabolism generates ATP and precursors for the synthesis of macromolecules to assemble progeny viruses. Some compounds derived from glutamine are used in the synthesis of purines and pyrimidines. These latter compounds are precursors for the synthesis of nucleotides. Inhibitors of glutamine transport and metabolism are potential candidate antiviral drugs. Glutamine is also an essential nutrient for the functions of leukocytes (lymphocyte, macrophage, and neutrophil), including those in virus-infected patients. The increased glutamine requirement for immune cell functions occurs concomitantly with the high glutamine utilization by host cells in virus-infected patients. The development of antiviral drugs that target glutamine metabolism must then be specifically directed at virus-infected host cells to avoid negative effects on immune functions. Therefore, the aim of this review was to describe the landscape of cellular glutamine metabolism to search for potential candidates to inhibit glutamine transport or glutamine metabolism.

Glutamine supplementation versus functional overload in extensor digitorum longus muscle hypertrophy

Background Glutamine levels directly associate with total protein content in cultured skeletal muscle cells, whereas glutamine supplementation enhances skeletal muscle mass in catabolic experimental conditions. Methods We compared the effect of glutamine administration on Extensor Digitorum Longus muscle (EDL) weight, fiber cross-sectional area (CSA), contractile activity, and protein metabolism signaling with a functional overload-induced skeletal muscle hypertrophy protocol. Results Glutamine supplementation raised the predominance of EDL muscle fibers with CSA between 1001 and 2000 μm2 (49.7 %), the p-4E-BP1/total 4E-BP1 ratio, and the effect of overload on resistance to fatigue. The proportion of the EDL muscle fiber CSA distribution for the combination of both treatments was similar to that induced by overload or glutamine separately; 54.3 % muscle fibers with CSA between 1001 and 2000 μm². Glutamine supplementation did not markedly affect the changes induced by overload on protein synthesis signaling pathways, except for a further increase of the p-4E-BP1/total 4E-BP1 ratio. Conclusions The effect of glutamine on EDL muscle fiber CSA distribution and protein synthesis signaling mimicked the response to overload. The association of glutamine and overload induced EDL muscle hypertrophy further increased the resistance to fatigue.

Marathon Race Affects Neutrophil Surface Molecules: Role of Inflammatory Mediators

The fatigue induced by marathon races was observed in terms of inflammatory and immunological outcomes. Neutrophil survival and activation are essential for inflammation resolutionand contributes directly to the pathogenesis of many infectious and inflammatory conditions.nThe aim of this study was to investigate the effect of marathon races on surface moleculesrelated to neutrophil adhesion and extrinsic apoptosis pathway and its association with inflammatory markers. We evaluated 23 trained male runners at the São Paulo International Marathon 2013. The following components were measured: hematological and inflammatory mediators, muscle damage markers, and neutrophil function. The marathon raceinduced an increased leukocyte and neutrophil counts; creatine kinase (CK), lactate dehydrogenase(LDH), CK-MB, interleukin (IL)-6, IL-10, and IL-8 levels. C-reactive protein(CRP), IL-12, and tumor necrosis factor (TNF)-α plasma concentrations were significantlyhigher 24 h and 72 h after the marathon race. Hemoglobin and hematocrit levels decreased72 h after the marathon race. We also observed an increased intercellular adhesion molecule-1(ICAM-1) expression and decreasedTNF receptor-1 (TNFR1) expression immediatelyafter and 24 h after the marathon race. We observed an increased DNA fragmentation and L-selectin and Fas receptor expressions in the recovery period, indicating a possibleslow rolling phase and delayed neutrophil activation and apoptosis. Marathon racing affectsneutrophils adhesion and survival in the course of inflammation, supporting the “openwindow”post-exercise hypothesis...