Glutamine in the pathogenesis of hepatic encephalopathy: The Trojan horse hypothesis revisited

Neurochemical Research

Volumn 39, Issue 3, 2014, Pages 593-598

  Rama Rao, Kakulavarapu V ^a   Norenberg, Michael D ^a,b  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

6 Diazo 5 oxo l norleucine (DON); Ammonia; Astrocytes; Glutaminase; Glutamine; Hepatic encephalopathy; l Histidine; Mitochondrial permeability transition; Oxidative stress

Indexed keywords

AMMONIA; GLUTAMATE AMMONIA LIGASE; GLUTAMINE;

ASTROCYTE; BRAIN MITOCHONDRION; HEPATIC ENCEPHALOPATHY; HUMAN; IMMUNOHISTOCHEMISTRY; MITOCHONDRIAL PERMEABILITY; NITRATIVE STRESS; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; PRIORITY JOURNAL; REVIEW;

EQUIDAE;

AMMONIA; ANIMALS; ASTROCYTES; GLUTAMINE; HEPATIC ENCEPHALOPATHY; HUMANS; MITOCHONDRIA; STRESS, PHYSIOLOGICAL;

EID: 84896689426     PISSN: 03643190     EISSN: 15736903     Source Type: Journal    
DOI: 10.1007/s11064-012-0955-2     Document Type: Review

References (54)

1. Williams R (1973) Hepatic encephalopathy. J R Coll Physicians Lond 8:63-74
2. Jones EA, Weissenborn K (1997) Neurology and the liver. J Neurol Neurosurg Psychiatr 63:279-293 (Pubitemid 27412365)
3. Capocaccia L, Angelico M (1991) Fulminant hepatic failure. Clinical features, etiology, epidemiology, and current management. Dig Dis Sci 36:775-779
4. Hoofnagle JH, Carithers RL Jr, Shapiro C, Ascher N (1995) Fulminant hepatic failure: summary of a workshop. Hepatology 21:240-252
5. Escorsell A, Mas A, de la Mata M (2007) Acute liver failure in Spain: analysis of 267 cases. Liver Transpl 13:1389-1395 (Pubitemid 47629571)
6. Lee WM, Squires RH Jr, Nyberg SL, Doo E, Hoofnagle JH (2008) Acute liver failure: summary of a workshop. Hepatology 47:1401-1415 (Pubitemid 351547926)
7. Lee WM (1994) Acute liver failure. Am J Med 96:3S-9S
8. Norenberg MD (1987) The role of astrocytes in hepatic encephalopathy. Neurochem Pathol 6:13-33
9. Martinez-Hernandez A, Bell KP, Norenberg MD (1977) Glutamine synthetase: glial localization in brain. Science 195:1356-1358 (Pubitemid 8056735)
10. Hourani BT, Hamlin EM, Reynolds TB (1971) Cerebrospinal fluid glutamine as a measure of hepatic encephalopathy. Arch Intern Med 127:1033-1036
11. Record CO, Buxton B, Chase RA, Curzon G, Murray-Lyon IM, Williams R (1976) Plasma and brain amino acids in fulminant hepatic failure and their relationship to hepatic encephalopathy. Eur J Clin Invest 6:387-394
12. McConnell JR, Antonson DL, Ong CS, Chu WK, Fox IJ, Heffron TG, Langnas AN, Shaw BW Jr (1995) Proton spectroscopy of brain glutamine in acute liver failure. Hepatology 22:69-74
13. Norenberg MD, Rao KV, Jayakumar AR (2005) Mechanisms of ammonia-induced astrocyte swelling. Metab Brain Dis 20:303-318 (Pubitemid 43029804)
14. Norenberg MD, Jayakumar AR, Rama Rao KV, Panickar KS (2007) New concepts in the mechanism of ammonia-induced astrocyte swelling. Metab Brain Dis 22:219-234 (Pubitemid 47624314)
15. O'Grady JG, Williams R (1986) Management of acute liver failure. Schweiz Med Wochenschr 116:541-544 (Pubitemid 16141928)
16. Rolando N, Wade J, Davalos M, Wendon J, Philpott-Howard J, Williams R (2000) The systemic inflammatory response syndrome in acute liver failure. Hepatology 32:734-739
17. Haussinger D, Schliess F (2005) Astrocyte swelling and protein tyrosine nitration in hepatic encephalopathy. Neurochem Int 47:64-70 (Pubitemid 40848694)
18. Haussinger D, Gorg B (2010) Interaction of oxidative stress, astrocyte swelling and cerebral ammonia toxicity. Curr Opin Clin Nutr Metab Care 13:87-92
19. Norenberg MD, Rama Rao KV, Jayakumar AR (2009) Signaling factors in the mechanism of ammonia neurotoxicity. Metab Brain Dis 24:103-117
20. Albrecht J, Norenberg MD (2006) Glutamine: a Trojan horse in ammonia neurotoxicity. Hepatology 44:788-794 (Pubitemid 46489541)
21. Rama Rao KV, Jayakumar AR, Norenberg MD (2012) Glutamine in the pathogenesis of acute hepatic encephalopathy. Neurochem Int 61:575-580
22. Pearlman DM (1957) Ammonia metabolism and hepatic coma. NY State J Med 57:3162-3166
23. Walshe JM, De Carli L, Davidson CS (1958) Some factors influencing cerebral ammonia production in relation to hepatic coma. Clin Sci (Lond) 17:27-36
24. McDermot W (1958) The role of ammonia intoxication in hepatic coma. Bull N Y Acad Med 34:357-365
25. Warren KS, Schenker S (1964) Effect of an inhibitor of glutamine synthesis (methionine sulfoximine) on ammonia toxicity and metabolism. J Lab Clin Med 64:442-449
26. Hawkins RA, Jessy J (1991) Hyperammonaemia does not impair brain function in the absence of net glutamine synthesis. Biochem J 277(Pt 3):697-703
27. Takahashi H, Koehler RC, Hirata T, Brusilow SW, Traystman RJ (1992) Restoration of cerebrovascular CO2 responsivity by glutamine synthesis inhibition in hyperammonemic rats. Circ Res 71:1220-1230
28. Takahashi H, Koehler RC, Brusilow SW, Traystman RJ (1991) Inhibition of brain glutamine accumulation prevents cerebral edema in hyperammonemic rats. Am J Physiol 261:H825-H829
29. Blei AT, Olafsson S, Therrien G, Butterworth RF (1994) Ammonia-induced brain edema and intracranial hypertension in rats after portacaval anastomosis. Hepatology 19:1437-1444 (Pubitemid 24166466)
30. Willard-Mack CL, Koehler RC, Hirata T, Cork LC, Takahashi H, Traystman RJ, Brusilow SW (1996) Inhibition of glutamine synthetase reduces ammonia-induced astrocyte swelling in rat. Neuroscience 71:589-599 (Pubitemid 26067021)
31. Norenberg MD, Bender AS (1994) Astrocyte swelling in liver failure: role of glutamine and benzodiazepines. Acta Neurochir Suppl (Wien) 60:24-27
32. Brusilow SW (2002) Hyperammonemic encephalopathy. Medicine (Baltimore) 81:240-249
33. Lockwood AH, Yap EW, Rhoades HM, Wong WH (1991) Altered cerebral blood flow and glucose metabolism in patients with liver disease and minimal encephalopathy. J Cereb Blood Flow Metab 11:331-336
34. Cordoba J, Crespin J, Gottstein J, Blei AT (1999) Mild hypothermia modifies ammonia-induced brain edema in rats after portacaval anastomosis. Gastroenterology 116:686-693 (Pubitemid 29106777)
35. Chatauret N, Zwingmann C, Rose C, Leibfritz D, Butterworth RF (2003) Effects of hypothermia on brain glucose metabolism in acute liver failure: a H/C-nuclear magnetic resonance study. Gastroenterology 125:815-824 (Pubitemid 37070699)
36. Zwingmann C, Chatauret N, Rose C, Leibfritz D, Butterworth RF (2004) Selective alterations of brain osmolytes in acute liver failure: protective effect of mild hypothermia. Brain Res 999:118-123 (Pubitemid 38121457)
37. Jayakumar AR, Rao KV, Murthy ChR, Norenberg MD (2006) Glutamine in the mechanism of ammonia-induced astrocyte swelling. Neurochem Int 48:623-628
38. Desjardins P, Du T, Jiang W, Peng L, Butterworth RF (2012) Pathogenesis of hepatic encephalopathy and brain edema in acute liver failure: role of glutamine redefined. Neurochem Int 60:690-696
39. Tofteng F, Hauerberg J, Hansen BA, Pedersen CB, Jorgensen L, Larsen FS (2006) Persistent arterial hyperammonemia increases the concentration of glutamine and alanine in the brain and correlates with intracranial pressure in patients with fulminant hepatic failure. J Cereb Blood Flow Metab 26:21-27 (Pubitemid 41818066)
40. Michalak A, Rose C, Butterworth J, Butterworth RF (1996) Neuroactive amino acids and glutamate (NMDA) receptors in frontal cortex of rats with experimental acute liver failure. Hepatology 24:908-913 (Pubitemid 26334293)
41. Zieminska E, Dolinska M, Lazarewicz JW, Albrecht J (2000) Induction of permeability transition and swelling of rat brain mitochondria by glutamine. Neurotoxicology 21:295-300 (Pubitemid 30436427)
42. Rama Rao KV, Jayakumar AR, Norenberg MD (2003) Induction of the mitochondrial permeability transition in cultured astrocytes by glutamine. Neurochem Int 43:517-523 (Pubitemid 36561307)
43. Murthy CR, Rama Rao KV, Bai G, Norenberg MD (2001) Ammonia-induced production of free radicals in primary cultures of rat astrocytes. J Neurosci Res 66:282-288 (Pubitemid 32912297)
44. Albrecht J, Zielinska M, Norenberg MD (2010) Glutamine as a mediator of ammonia neurotoxicity: a critical appraisal. Biochem Pharmacol 80:1303-1308
45. Rama Rao KV, Reddy PV, Tong X, Norenberg MD (2010) Brain edema in acute liver failure: inhibition by L -histidine. Am J Pathol 176:1400-1408
46. Ruszkiewicz J, Fresko I, Hilgier W, Albrecht J (2012) Decrease of glutathione content in the prefrontal cortical mitochondria of rats with acute hepatic encephalopathy: prevention by histidine. Metab Brain Dis (in press)
47. Brusilow SW, Koehler RC, Traystman RJ, Cooper AJ (2010) Astrocyte glutamine synthetase: importance in hyperammonemic syndromes and potential target for therapy. Neurotherapeutics 7:452-470
48. Kanamori K, Ross BD (1995) In vivo activity of glutaminase in the brain of hyperammonaemic rats measured by 15 N nuclear magnetic resonance. Biochem J 305(Pt 1):329-336
49. Wurdig S, Kugler P (1991) Histochemistry of glutamate metabolizing enzymes in the rat cerebellar cortex. Neurosci Lett 130:165-168
50. Schousboe A, Hertz L, Svenneby G, Kvamme E (1979) Phosphate activated glutaminase activity and glutamine uptake in primary cultures of astrocytes. J Neurochem 32:943-950 (Pubitemid 9128598)
51. Kvamme E, Svenneby G, Hertz L, Schousboe A (1982) Properties of phosphate activated glutaminase in astrocytes cultured from mouse brain. Neurochem Res 7:761-770 (Pubitemid 12038418)
52. Hogstad S, Svenneby G, Torgner IA, Kvamme E, Hertz L, Schousboe A (1988) Glutaminase in neurons and astrocytes cultured from mouse brain: kinetic properties and effects of phosphate, glutamate, and ammonia. Neurochem Res 13:383-388
53. Kvamme E, Nissen-Meyer LS, Roberg BA, Torgner IA (2008) Novel form of phosphate activated glutaminase in cultured astrocytes and human neuroblastoma cells, PAG in brain pathology and localization in the mitochondria. Neurochem Res 33:1341-1345
54. Olalla L, Gutierrez A, Jimenez AJ, Lopez-Tellez JF, Khan ZU, Perez J, Alonso FJ, de la Rosa V, Campos-Sandoval JA, Segura JA, Aledo JC, Marquez J (2008) Expression of the scaffolding PDZ protein glutaminase-interacting protein in mammalian brain. J Neurosci Res 86:281-292 (Pubitemid 351196734)