In vitro study of uptake and synthesis of creatine and its precursors by cerebellar granule cells and astrocytes suggests some hypotheses on the physiopathology of the inherited disorders of creatine metabolism

BMC Neuroscience

Volumn 13, Issue 1, 2012, Pages

  Carducci, Claudia ^a,c   Carducci, Carla ^a   Santagata, Silvia ^a   Adriano, Enrico ^b   Artiola, Cristiana ^a   Thellung, Stefano ^b   Gatta, Elena ^b   Robello, Mauro ^b   Florio, Tullio ^b   Antonozzi, Italo ^a   Leuzzi, Vincenzo ^a   Balestrino, Maurizio ^b  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b UNIVERSITY OF GENOA   (Italy)

^c SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

Creatine transporter (CT1); Creatine transporter gene (SLC6A8); Energetic metabolism in CNS; L arginine:glycine amidinotransferase (AGAT); Mass spectrometry; S adenosylmethionine: guanidinoacetate n methyltransferase (GAMT)

Indexed keywords

AMIDINOTRANSFERASE; AMINO ACID TRANSPORTER; ARGININE; CREATINE; D3 CREATINE; GLYCINE; GUANIDINOACETIC ACID; GUANIDINOPROPIONIC ACID; METHYLTRANSFERASE; S ADENOSYLMETHIONINE; UNCLASSIFIED DRUG; GUANIDINOACETATE METHYLTRANSFERASE;

AMINO ACID SYNTHESIS; ANIMAL CELL; ANIMAL TISSUE; ARTICLE; ASTROCYTE; BRAIN LEVEL; CELL CULTURE; CEREBELLUM; CONTROLLED STUDY; CREATINE TRANSPORTER GENE; DISORDERS OF AMINO ACID AND PROTEIN METABOLISM; GENE; GENE EXPRESSION; GENETIC DISORDER; GENETIC TRANSCRIPTION; GRANULE CELL; IN VITRO STUDY; INHERITED DISORDER OF CREATINE METABOLISM; NONHUMAN; POLYMERASE CHAIN REACTION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN TRANSPORT; WISTAR RAT; ANIMAL; CYTOLOGY; METABOLISM; NERVE CELL; RAT;

ANIMALS; ASTROCYTES; CEREBELLUM; CREATINE; GUANIDINOACETATE N-METHYLTRANSFERASE; NEURONS; RATS; RATS, WISTAR; S-ADENOSYLMETHIONINE;

EID: 84860211105     PISSN: None     EISSN: 14712202     Source Type: Journal    
DOI: 10.1186/1471-2202-13-41     Document Type: Article

References (46)

1. Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev 2000, 80:1107-1212.
2. Balestrino M, Lensman M, Parodi M, Perasso L, Rebaudo R, Melani R, Polenov S, Cupello A. Role of creatine and phosphocreatine in neuronal protection from anoxic and ischemic damage. Amino Acids 2002, 23:221-229.
3. Item CB, Stöckler-Ipsiroglu S, Stromberger C, Mühl A, Alessandrì MG, Bianchi MC, Fornai F, Cioni G. Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. Am J Hum Genet 2001, 69:1127-1133.
4. Stöckler S, Holzbach U, Hanefeld F, Marquartdt I, Helms G, Requart M, Hänicke W, Frahm J. Creatine deficiency in the brain: a new, treatable inborn error of metabolism. Pediatr Res 1994, 36:409-413.
5. Cecil KM, Salomons GS, Ball WS, Wong B, Chuck G, Verhoeven NM, Jakobs C, DeGraw TJ. Irreversible brain creatine deficiency with elevated serum and urine creatine: a creatine transporter defect?. Ann Neurol 2001, 49:401-404.
6. Salomons GS, van Dooren SJ, Verhoeven NM, Cecil KM, Ball WS, Degrauw TJ, Jakobs C. X-linked creatine-transporter gene (SLC6A8) defect: A new creatine-deficiency syndrome. Am J Hum Genet 2001, 68:1497-1500.
7. Bianchi MC, Tosetti M, Fornai F, Alessandri MG, Cipriani P, De Vito G, Canapicchi R. Reversible brain creatine deficiency in two sisters with normal blood creatine level. Ann Neurol 2000, 47:511-513.
8. Mercimek-Mahmutoglu S, Stoeckler-Ipsiroglu S, Adami A, Appleton R, Araújo HC, Duran M, Ensenauer R, Fernandez-Alvarez E, Garcia P, Grolik C, Item CB, Leuzzi V, Marquardt I, Mühl A, Saelke-Kellermann RA, Salomons GS, Schulze A, Surtees R, van der Knaap MS, Vasconcelos R, Verhoeven NM, Vilarinho L, Wilichowski E, Jakobs C. GAMT deficiency: features, treatment, and outcome in an inborn error of creatine synthesis. Neurology 2006, 67:480-494.
9. Battini R, Alessandrì MG, Leuzzi V, Moro F, Tosetti M, Bianchi MC, Cioni G. Arginine:glycine amidinotransferase (AGAT) deficiency in a newborn: early treatment can prevent phenotypic expression of the disease. J Pediatr 2006, 148:828-830.
10. Schulze A, Hoffmann GF, Bachert P, Kirsch S, Salomons GS, Verhoeven NM, Mayatepek E. Presymptomatic treatment of neonatal guanidinoacetate methyltransferase deficiency. Neurology 2006, 67:719-721.
11. Bianchi MC, Tosetti M, Battini R, Leuzzi V, Alessandri MG, Carducci C, Antonozzi I, Cioni G. Treatment monitoring of brain creatine deficiency syndromes: a 1H- and 31P-MR spectroscopy study. Am J Neuroradiol 2007, 28:548-554.
12. Leuzzi V, Alessandrì MG, Casarano M, Battini R, Cioni G. Arginine and glycine stimulate creatine synthesis in creatine transporter 1-deficient lymphoblasts. Anal Biochem 2008, 375:153-155.
13. Chilosi A, Leuzzi V, Battini R, Tosetti M, Ferretti G, Comparini A, Casarano M, Moretti E, Alessandri MG, Bianchi MC, Cioni G. Treatment with L-arginine improves neuropsychological disorders in a child with creatine transporter defect. Neurocase 2008, 14:151-161.
14. Fons C, Sempere A, Arias A, López-Sala A, Póo P, Pineda M, Mas A, Vilaseca MA, Salomons GS, Ribes A, Artuch R, Campistol J. Arginine supplementation in four patients with X-linked creatine transporter defect. J Inherit Metab Dis 2008, 31:724-728.
15. Braissant O, Henry H, Loup M, Eilers B, Bachmann C. Endogenous synthesis and transport of creatine in the rat brain: an in situ hybridization study. Brain Res Mol Brain Res 2001, 86:193-201.
16. Daly MM. Guanidinoacetate methyltransferase activity in tissues and cultured cells. Arch Biochem Biophys 1985, 236:576-584.
17. Dringen R, Verleysdonk S, Hamprecht B, Willker W, Leibfritz D, Brand A. Metabolism of glycine in primary astroglial cells: synthesis of creatine, serine, and glutathione. J Neurochem 1998, 70:835-840.
18. Tachikawa M, Fujinawa J, Takahashi M, Kasai Y, Fukaya M, Sakai K, Yamazaki M, Tomi M, Watanabe M, Sakimura K, Terasaki T, Hosoya K. Expression and possible role of creatine transporter in the brain at the blood-cerebrospinal fluid barrier as transporting protein of guanidinoacetate, an endogenous convulsant. J Neurochem 2008, 107:768-778.
19. Robello M, Amico C, Cupello A. Regulation of GABA-A receptor in cerebellar granule cells inculture: Differential involvement of kinase activities. Neuroscience 1993, 53:131-138.
20. Thellung S, Villa V, Corsaro A, Pellistri F, Venezia V, Russo C, Aceto A, Robello M, Florio T. ERK1/2 and p38 MAP kinases control prion protein fragment 90-231-induced astrocyte proliferation and microglia activation. GLIA 2007, 55:1469-1485.
21. Braissant O, Cagnon L, Monnet-Tschudi F, Speer O, Wallimann T, Honegger P, Henry H. Ammonium alters creatine transport and synthesis in a 3D culture of developing brain cells, resulting in secondary cerebral creatine deficiency. Eur J Neurosci 2008, 27:1673-1685.
22. Yuan J, Bennett BD, Rabinowitz JD. Kinetic flux profiling for quantitation of cellular metabolic fluxes. Nat Protoc 2008, 3:1328-1340.
23. Verhoeven NM, Schor DS, Roos B, Battini R, Stöckler-Ipsiroglu S, Salomons GS, Jakobs C. Diagnostic enzyme assay that uses stable isotope-labelled substrates to detect L-arginine:glycine amidinotransferase deficiency. Clin Chem 2003, 49:803-805.
24. Balestrino M, Gandolfo C, Perasso L. Controlling the flow of energy: inhibition and stimulation of the creatine transporter. Curr Enzym Inhib 2009, 5:223-233.
25. Saltarelli MD, Bauman AL, Moore KR, Bradley CC, Blakely RD. Expression of the rat brain creatine transporter in situ and in transfected HeLa cells. Dev Neurosci 1996, 18:524-534.
26. Hiel H, Happe HK, Warr WB, Morley BJ. Regional distribution of a creatine transporter in rat auditory brainstem: an in-situ hybridization study. Hear Res 1996, 98:29-37.
27. Braissant O, Henry H. AGAT, GAMT and SLC6A8 distribution in the central nervous system, in relation to creatine deficiency syndromes: A review. J Inherit Metab Dis 2008, 31:230-239.
28. Braissant O, Henry H, Villard AM, Speer O, Wallimann T, Bachmann C. Creatine synthesis and transport during rat embryogenesis: spatiotemporal expression of AGAT, GAMT and CT1. BMC Dev Biol 2005, 26:5-9.
29. Möller A, Hamprecht B. Creatine transport in cultured cells of rat and mouse brain. J Neurochem 1989, 52:544-550.
30. Acosta ML, Kalloniatis M, Christie DL. Creatine transporter localization in developing and adult retina: importance of creatine to retinal function. Am J Physiol Cell Physiol 2005, 289:1015-1023.
31. Mak CS, Waldvogel HJ, Dodd JR, Gilbert RT, Lowe MT, Birch NP, Faull RL, Mak Christie DL. Immunohistochemical localisation of the creatine transporter in the rat brain. Neuroscience 2009, 163:571-585.
32. Stoll J, Wadhwani KC, Smith QR. Identification of the cationic amino acid transporter (systemy+) of the rat blood-brain barrier. J Neurochem 1993, 60:1956-1959.
33. Braissant O, Gotoh T, Loup M, Mori M, Bachmann C. L-arginine uptake, the citrulline-NO cycle and arginase II in the rat brain: an in situ hybridization study. Brain Res Mol Brain Res 1999, 70:231-241.
34. O'Kane RL, Viña JR, Simpson I, Zaragozá R, Mokashi A, Hawkins RA. Cationic amino acid transport across the blood-brain barrier is mediated exclusively by system y+. Am J Physiol Endocrinol Metab 2006, 291:E412-E419.
35. Hosoya K, Ichikawa T, Akanuma S, Hirose S, Tachikawa M. Glycine and L-arginine transport in cultured Müller glial cells (TR-MUL). Neurochem Int 2010, 57:262-268.
36. Braissant O, Béard E, Torrent C, Henry H. Dissociation of AGAT, GAMT and SLC6A8 in CNS: Relevance to creatine deficiency syndromes. Neurobiol Dis 2010, 37:423-433.
37. Lunardi G, Parodi A, Perasso L, Pohvozcheva AV, Scarrone S, Adriano E, Florio T, Gandolfo C, Cupello A, Burov SV, Balestrino M. The creatine transporter mediates the uptake of creatine bybrain tissue, but not the uptake of two creatine-derived compounds. Neuroscience 2006, 142:991-997.
38. Tachikawa M, Kasai Y, Yokoyama R, Fujinawa J, Ganapathy V, Terasaki T, Hosoya K. The blood-brain barrier transport and cerebral distribution of guanidinoacetate in rats: involvement of creatine and taurine transporters. J Neurochem 2009, 111:499-509.
39. Ohtsuki S, Tachikawa M, Takanaga H, Shimizu H, Watanabe M, Hosoya K, Ohtsuki Terasaki T. The blood-brain barrier creatine transporter is a major pathway for supplying creatine to the brain. J Cereb Blood Flow Metab 2002, 22:1327-1335.
40. de Grauw TJ, Salomons GS, Cecil KM, Chuck G, Newmeyer A, Schapiro MB, Jakobs C. Congenital creatine transporter deficiency. Neuropediatrics 2002, 33:232-238.
41. Dechent P, Pouwels PJ, Wilken B, Hanefeld F, Frahm J. Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. Am J Physiol 1999, 277:R698-R704.
42. Ipsiroglu OS, Stromberger C, Ilas J, Hoger H, Muhl A, Stockler-Ipsiroglu S. Changes of tissue creatine concentrations upon oral supplementation of creatine-monohydrate in various animal species. Life Sci 2001, 69:1805-1815.
43. Perasso L, Cupello A, Lunardi GL, Principato C, Gandolfo C, Balestrino M. Kinetics of creatine in blood and brain after intraperitoneal injection in the rat. Brain Research 2003, 974:37-42.
44. Kan HE, Meeuwissen E, Veltien A, Isbrandt D, Heerschap A. Creatine uptake kinetics in brain and skeletal muscle of GAMT deficient knockout mice. Proc Intl Soc Mag Reson Med 2006, 14:1484.
45. Almeida LS, Verhoeven NM, Roos B, Valongo C, Cardoso ML, Vilarinho L, Salomons GS, Jakobs C. Creatine and guanidinoacetate: diagnostic markers for inborn errors in creatine biosynthesis and transport. Mol Genet Metab 2004, 82:214-219.
46. Skelton MR, Schaefer TL, Graham DL, Degrauw TJ, Clark JF, Williams MT, Vorhees CV. Creatine Transporter (CrT; Slc6a8) knocout mice as a model of human CrT deficiency. PloS One Jan 2011, 13:e16187.