2012, Number 2
<< Back Next >>
Rev Invest Clin 2012; 64 (2)
Changes in peripheral blood mononuclear cells glutamine synthetase mRNA after exercise in healthy volunteers: exploring an alternative proposal for non hepatic ammonia metabolism
Duarte-Rojo A, Torres-Vega MÁ, Villamil-Ramírez H, Estradas J, Domínguez-López A, Sánchez-Muñoz F, Orea-Tejeda A, Castillo-Martínez L, Miliar-García Á, Macías-Rodríguez RU, Torre A
Language: Spanish
References: 38
Page: 164-172
PDF size: 240.31 Kb.
ABSTRACT
Background. Glutamine synthetase (GS) plays a central role in the inter-organ metabolism of ammonia and hepatic encephalopathy. The main objective of the present work was to disclose the possible effect of exercise on GS mRNA expression in peripheral blood mononuclear cells (PBMC) within a group of healthy volunteers.
Material and methods. PBMC were studied instead of skeletal muscle because of ethical concerns. Characterization of GS in lymphocytes was carried out by indirect immunofluorescence and Western blot. After a pilot trial, expression of GS mRNA in PBMC was assayed by serial measurements in healthy volunteers who had exercised on a treadmill, and on a control group who had not. Muscle mass was estimated by bioimpedance.
Results. Cytoplasmic GS had a molecular weight of 44 kDa. Serial measurements of its mRNA demonstrated an increase in the treadmill (n = 29), but not in the control group (n = 13) (p ‹ 0.05). Peak expression occurred at 1 h in males and at 6 h in females. There was a positive correlation between muscle mass and the increase of the enzyme mRNA after exercise.
Conclusion. Exercise can increase the expression of GS mRNA in PBMC in healthy volunteers. Based on these preliminary results and on wellestablished physiological concepts, a hypothesis for nonhepatic ammonia metabolism is conceived. In the future could become part of the treatment of low-grade hepatic encephalopathy.
REFERENCES
Häussinger D, Schliess F. Pathogenetic mechanisms of hepatic encephalopathy. Gut 2008; 57: 1156-65.
Ortiz M, Jacas C, Cordoba J. Minimal hepatic encephalopathy: diagnosis, clinical significance and recommendations. J Hepatol 2005; S45-S53.
Poordad FF. Review article: the burden of hepatic encephalopathy. Aliment Pharmacol Ther 2007; 25(Suppl. 1): 3-9.
Stewart CA, Cerhan J. Hepatic encephalopathy: a dynamic or static condition. Metab Brain Dis 2005; 20: 193-204.
Albrecht J, Norenberg MD. Glutamine: a Trojan horse in ammonia neurotoxicity. Hepatology 2006; 44: 788-94.
Häussinger D. Nitrogen metabolism in liver: structural and functional organization and physiological relevance. Biochem J 1990; 267: 281-90.
Rose C, Felipo V. Limited capacity for ammonia renoval by brain in chronic liver failure: potential role of nitric oxide. Metab Brain Dis 2005; 20: 275-83.
Kaiser S, Gerok W, Häussinger D. Ammonia and glutamine metabolism in human liver slices: new aspects on the pathogenesis of hyperammonemia in chronic liver disease. Eur J Clin Invest 1988; 18: 535-42.
Desjardins P, Rao KV, Michalak A, et al. Effect of portocaval anastomosis on glutamine synthetase protein and gene expression in brain, liver and skeletal muscle. Metab Brain Dis 1999; 14: 273-80.
Jiang Q, Jiang XH, Zheng MH, et al. L-Ornithine-l-aspartate in the management of hepatic encephalopathy: a meta-analysis. J Gastroenterol Hepatol 2009; 24: 9-14.
Gebhardt R, Beckers G, Gaunitz F, et al. Treatment of cirrhotic rats with L-ornithine-L-aspartate enhances urea synthesis and lowers serum ammonia levels. J Pharmacol Exp Ther 1997; 283: 1-6.
Rose C, Michalak A, Rao KV, et al. L-ornithine-L-aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure. Hepatology 1999; 30: 636-40.
Santos RV, Caperuto EC, Costa Rosa LF. Effects of acute exhaustive physical exercise upon glutamine metabolism of lymphocytes from trained rats. Life Sci 2007; 80: 573-8.
Miyazaki T, Matsuzaki Y, Karube M, et al. Amino acid ratios in plasma and tissues in a rat model of liver cirrhosis before and after exercise. Hepatol Res 2003; 27: 230-7.
van Straaten HW, He Y, van Duist MM, et al. Cellular concentrations of glutamine synthetase in murine organs. Biochem Cell Biol 2006; 84: 215-31.
Curi R, Newsholme P, Procopio J, et al. Glutamine, gene expression, and cell function. Front Biosci 2007; 12: 344-57.
Zierath JR, Hawley JA. Skeletal muscle fiber type: influence on contractile and metabolic properties. PLoS Biol 2004; 2: e348.
Olde Damink SW, Deutz NE, Dejong CH, et al. Interorgan ammonia metabolism in liver failure. Neurochem Int 2002; 41: 177-88.
Chatauret N, Butterworth RF. Effects of liver failure on interorgan trafficking of ammonia: implications for the treatment of hepatic encephalopathy. J Gastroenterol Hepatol 2004; 19: S219-S223.
Zeibig J, Karlic H, Lohninger A, et al. Do blood cells mimic gene expression profile alterations known to occur in muscular adaptation to endurance training? Eur J Appl Physiol 2005; 95: 96-104.
Lohman TG, Roche AF, Martorell R. Anthropometric standardization reference manual. Abridged (Ed.). Champaign, IL: Human Kinetics; 1991, p. 3-7.
Lukaski HC, Johnson PE, Bolonchuk WW, et al. Assessment of fat-free mass using bioelectrical impedance measurements of the human body. Am J Clin Nutr 1985; 41: 810-7.
Macias N, Alemán-Mateo H, Esparza-Romero J, et al. Body fat measurement by bioelectrical impedance versus air displacement plethysmography: a cross-validation study to design bioelectrical impedance equations in Mexican adults. Nutr J 2007; 6: 18.
Mouritzen P, Noerholm M, Nielsen PS, et al. ProbeLibrary: a new method for faster design and execution of quantitative real-time PCR. Nat Methods 2005; 2: 313-6.
Matthews JN, Altman DG, Campbell MJ, et al. Analysis of serial measurements in medical research. BMJ 1990; 300: 230-5.
Häberle J, Görg B, Rutsch F, et al. Congenital glutamine deficiency with glutamine synthetase mutations. N Engl J Med 2005; 353: 1926-33.
Aggarwal D, Freake HC, Soliman GA, et al. Validation of using gene expression in mononuclear cells as a marker for hepatic cholesterol metabolism. Lipids Health Dis 2006; 5: 22.
Calder PC. Fuel utilization by cells of the immune system. Proc Nutr Soc 1995; 54: 65-82.
Newsholme P, Curi R, Pithon Curi TC, et al. Glutamine metabolism by lymphocytes, macrophages, and neutrophils: its importance in health and disease. J Nutr Biochem 1999; 10: 316-24.
Ganda OP, Ruderman NB. Muscle nitrogen metabolism in chronic hepatic insufficiency. Metabolism 1976; 25: 427-35.
Hod G, Chaouat M, Haskel Y, et al. Ammonia uptake by skeletal muscle in the hyperammonaemic rat. Eur J Clin Invest 1982; 12: 445-50.
Leweling H, Breitkreutz R, Behne F, et al. Hyperammonemia- induced depletion of glutamate and branched-chain amino acids in muscle and plasma. J Hepatol 1996; 25: 756-62.
Chatauret N, Desjardins P, Zwingmann C, et. al. Direct molecular and spectroscopic evidence for increased ammonia removal capacity of skeletal muscle in acute liver failure. J Hepatol 2006; 44: 1083-8.
Rao VKR, Desjardins P, Rose P, et al. Increased glutamine synthetase expression in skeletal muscle: an important alternative pathway for ammonia removal in liver failure. Hepatology 1999; 29: 162A.
Clemmesen JO, Kondrup J, Ott P. Splanchnic and leg exchange of amino acids and ammonia in acute liver failure. Gastroenterology 2000; 118: 1131-9.
Rose BD, Post TW. Clinical physiology of acid-base and electrolyte disorders. 5th. Ed. New York: McGraw-Hill; 2001.
Denis C, Linossier MT, Dormois D, et al. Effects of endurance training on hyperammonaemia during a 45-min constant exercise intensity. Eur J Appl Physiol Occup Physiol 1989; 59: 268-72.
Yuan Y, Chan KM. A longitudinal study on the ammonia threshold in junior cyclists. Br J Sports Med 2004; 38: 115-9.
Full text