Prion protein regulates glutathione metabolism and neural glutamate and cysteine uptake via excitatory amino acid transporter 3

Journal of Neurochemistry

Volumn 133, Issue 4, 2015, Pages 558-571

  Guitart, Kathrin ^a   Loers, Gabriele ^a   Schachner, Melitta ^b,c   Kleene, Ralf ^a  

^a UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^b RUTGERS UNIVERSITY   (United States)

^c SHANTOU UNIVERSITY MEDICAL COLLEGE   (China)

Author keywords

cellular stress; excitatory amino acid transporter; glutathione; multi drug resistance protein; prion protein; glutamyl transpeptidase

Indexed keywords

CYSTEINE; EXCITATORY AMINO ACID TRANSPORTER 3; GAMMA GLUTAMYLTRANSFERASE; GLUTAMIC ACID; GLUTATHIONE; MULTIDRUG RESISTANCE PROTEIN 1; PRION PROTEIN; AMINO ACID RECEPTOR AFFECTING AGENT; CALCEIN; FLUORESCEIN DERIVATIVE; PRION;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; ASTROCYTE; CONTROLLED STUDY; ENZYME ACTIVITY; EXCITOTOXICITY; FEMALE; GLUTATHIONE METABOLISM; MACROGLIA; MALE; MOUSE; NERVE CELL; NERVE CELL NECROSIS; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; ANIMAL; C57BL MOUSE; CELL CULTURE; CEREBELLUM; CHO CELL LINE; CRICETULUS; CYTOLOGY; DRUG EFFECTS; GENETICS; METABOLISM; MUTATION; PHYSIOLOGY; PRION; TRANSGENIC MOUSE;

ANIMALS; ASTROCYTES; CELLS, CULTURED; CEREBELLUM; CHO CELLS; CRICETULUS; CYSTEINE; EXCITATORY AMINO ACID AGENTS; EXCITATORY AMINO ACID TRANSPORTER 3; FEMALE; FLUORESCEINS; GLUTAMIC ACID; GLUTATHIONE; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MUTATION; NEURONS; PRIONS;

EID: 84927626071     PISSN: 00223042     EISSN: 14714159     Source Type: Journal    
DOI: 10.1111/jnc.13071     Document Type: Article

References (83)

1. Aoyama K., Suh S. W., Hamby A. M., Liu J., Chan W. Y., Chen Y., and, Swanson R. A., (2006) Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. Nat. Neurosci. 9, 119-126.
2. Arriza J. L., Fairman W. A., Wadiche J. I., Murdoch G. H., Kavanaugh M. P., and, Amara S. G., (1994) Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex. J. Neurosci. 14, 5559-5569.
3. Arriza J. L., Eliasof S., Kavanaugh M. P., and, Amara S. G., (1997) Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance. Proc. Natl Acad. Sci. USA 94, 4155-4160.
4. Bains J. S., and, Shaw C. A., (1997) Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death. Brain Res. Brain Res. Rev. 25, 335-358.
5. Bharath S., Hsu M., Kaur D., Rajagopalan S., and, Andersen J. K., (2002) Glutathione, iron and Parkinson's disease. Biochem. Pharmacol. 64, 1037-1048.
6. Brown D. R., (2004) Role of the prion protein in copper turnover in astrocytes. Neurobiol. Dis. 15, 534-543.
7. Bueler H., Fischer M., Lang Y., Bluethmann H., Lipp H. P., DeArmond S. J., Prusiner S. B., Aguet M., and, Weissmann C., (1992) Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature 356, 577-582.
8. Burns C. S., Aronoff-Spencer E., Dunham C. M., et al., (2002) Molecular features of the copper binding sites in the octarepeat domain of the prion protein. Biochemistry 41, 3991-4001.
9. Chen Y., and, Swanson R. A., (2003) The glutamate transporters EAAT2 and EAAT3 mediate cysteine uptake in cortical neuron cultures. J. Neurochem. 84, 1332-1339.
10. Chen S., Mantei N., Dong L., and, Schachner M., (1999) Prevention of neuronal cell death by neural adhesion molecules L1 and CHL1. J. Neurobiol. 38, 428-439.
11. Chen S., Mange A., Dong L., Lehmann S., and, Schachner M., (2003) Prion protein as trans-interacting partner for neurons is involved in neurite outgrowth and neuronal survival. Mol. Cell Neurosci. 22, 227-233.
12. Collinge J., (1997) Human prion diseases and bovine spongiform encephalopathy (BSE). Hum. Mol. Genet. 6, 1699-1705.
13. Demart S., Fournier J. G., Creminon C., Frobert Y., Lamoury F., Marce D., Lasmezas C., Dormont D., Grassi J., and, Deslys J. P., (1999) New insight into abnormal prion protein using monoclonal antibodies. Biochem. Biophys. Res. Commun. 265, 652-657.
14. Do K. Q., Trabesinger A. H., Kirsten-Kruger M., Lauer C. J., Dydak U., Hell D., Holsboer F., Boesiger P., and, Cuenod M., (2000) Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo. Eur. J. Neurosci. 12, 3721-3728.
15. Dringen R., (2000) Metabolism and functions of glutathione in brain. Prog. Neurobiol. 62, 649-761.
16. Dringen R., and, Hirrlinger J., (2003) Glutathione pathways in the brain. Biol. Chem. 384, 505-516.
17. Dringen R., Pfeiffer B., and, Hamprecht B., (1999) Synthesis of the antioxidant glutathione in neurons: supply by astrocytes of CysGly as precursor for neuronal glutathione. J. Neurosci. 19, 562-569.
18. Dringen R., Gutterer J. M., and, Hirrlinger J., (2000) Glutathione metabolism in brain metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species. Eur. J. Biochem. 267, 4912-4916.
19. Dringen R., Gutterer J. M., Gros C., and, Hirrlinger J., (2001) Aminopeptidase N mediates the utilization of the GSH precursor CysGly by cultured neurons. J. Neurosci. Res. 66, 1003-1008.
20. Fairman W. A., Vandenberg R. J., Arriza J. L., Kavanaugh M. P., and, Amara S. G., (1995) An excitatory amino-acid transporter with properties of a ligand-gated chloride channel. Nature 375, 599-603.
21. Finkel T., and, Holbrook N. J., (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408, 239-247.
22. Flechsig E., Shmerling D., Hegyi I., Raeber A. J., Fischer M., Cozzio A., von Mering C., Aguzzi A., and, Weissmann C., (2000) Prion protein devoid of the octapeptide repeat region restores susceptibility to scrapie in PrP knockout mice. Neuron 27, 399-408.
23. Forloni G., Angeretti N., Chiesa R., Monzani E., Salmona M., Bugiani O., and, Tagliavini F., (1993) Neurotoxicity of a prion protein fragment. Nature 362, 543-546.
24. Fuhrmann M., Bittner T., Mitteregger G., Haider N., Moosmang S., Kretzschmar H., and, Herms J., (2006) Loss of the cellular prion protein affects the Ca2+ homeostasis in hippocampal CA1 neurons. J. Neurochem. 98, 1876-1885.
25. Gauthier C., Ozvegy-Laczka C., Szakacs G., Sarkadi B., and, Di Pietro A., (2013) ABCG2 is not able to catalyze glutathione efflux and does not contribute to GSH-dependent collateral sensitivity. Front. Pharmacol. 4, 138.
26. Govaerts C., Wille H., Prusiner S. B., and, Cohen F. E., (2004) Evidence for assembly of prions with left-handed beta-helices into trimers. Proc. Natl Acad. Sci. USA 101, 8342-8347.
27. Gu M., Owen A. D., Toffa S. E., Cooper J. M., Dexter D. T., Jenner P., Marsden C. D., and, Schapira A. H., (1998) Mitochondrial function, GSH and iron in neurodegeneration and Lewy body diseases. J. Neurol. Sci. 158, 24-29.
28. Hayes D., Wiessner M., Rauen T., and, McBean G. J., (2005) Transport of L-[14C]cystine and L-[14C]cysteine by subtypes of high affinity glutamate transporters over-expressed in HEK cells. Neurochem. Int. 46, 585-594.
29. Himi T., Ikeda M., Yasuhara T., Nishida M., and, Morita I., (2003) Role of neuronal glutamate transporter in the cysteine uptake and intracellular glutathione levels in cultured cortical neurons. J. Neural. Transm. 110, 1337-1348.
30. Hinton C., Antony H., Hashimi S. M., Munn A., and, Wei M. Q., (2013) Significance of prion and prion-Like proteins in cancer development, progression and multi-drug resistance. Curr. Cancer Drug Targets 13, 895-904.
31. Hirrlinger J., König J., Keppler D., Lindenau J., Schulz J. B., and, Dringen R., (2001) The multidrug resistance protein MRP1 mediates the release of glutathione disulfide from rat astrocytes during oxidative stress. J. Neurochem. 76, 627-636.
32. Hirrlinger J., König J., and, Dringen R., (2002) Expression of mRNAs of multidrug resistance proteins (Mrps) in cultured rat astrocytes, oligodendrocytes, microglial cells and neurones. J. Neurochem. 82, 716-719.
33. Hirrlinger J., Moeller H., Kirchhoff F., and, Dringen R., (2005) Expression of multidrug resistance proteins (Mrps) in astrocytes of the mouse brain: a single cell RT-PCR study. Neurochem. Res. 30, 1237-1244.
34. Holmseth S., Dehnes Y., Huang Y. H., et al., (2012) The density of EAAC1 (EAAT3) glutamate transporters expressed by neurons in the mammalian CNS. J. Neurosci. 32, 6000-6013.
35. Jenner P., and, Olanow C. W., (1998) Understanding cell death in Parkinson's disease. Ann. Neurol. 44, S72-S84.
36. Kanai Y., and, Hediger M. A., (2003) The glutamate and neutral amino acid transporter family: physiological and pharmacological implications. Eur. J. Pharmacol. 479, 237-247.
37. Kleene R., Loers G., Langer J., Frobert Y., Buck F., and, Schachner M., (2007) Prion protein regulates glutamate-dependent lactate transport of astrocytes. J. Neurosci. 27, 12331-12340.
38. Koch H. P., Kavanaugh M. P., Esslinger C. S., Zerangue N., Humphrey J. M., Amara S. G., Chamberlin A. R., and, Bridges R. J., (1999) Differentiation of substrate and nonsubstrate inhibitors of the high-affinity, sodium-dependent glutamate transporters. Mol. Pharmacol. 56, 1095-1104.
39. Krebs B., Wiebelitz A., Balitzki-Korte B., Vassallo N., Paluch S., Mitteregger G., Onodera T., Kretzschmar H. A., and, Herms J., (2007) Cellular prion protein modulates the intracellular calcium response to hydrogen peroxide. J. Neurochem. 100, 358-367.
40. Lin C. L., Tzingounis A. V., Jin L., Furuta A., Kavanaugh M. P., and, Rothstein J. D., (1998) Molecular cloning and expression of the rat EAAT4 glutamate transporter subtype. Brain Res. Mol. Brain Res. 63, 174-179.
41. Loers G., Makhina T., Bork U., Dörner A., Schachner M., and, Kleene R., (2012) The interaction between cell adhesion molecule L1, matrix metalloproteinase 14, and adenine nucleotide translocator at the plasma membrane regulates L1-mediated neurite outgrowth of murine cerebellar neurons. J. Neurosci. 32, 3917-3930.
42. Makhina T., Loers G., Schulze C., Ueberle B., Schachner M., and, Kleene R., (2009) Extracellular GAPDH binds to L1 and enhances neurite outgrowth. Mol. Cell Neurosci. 41, 206-218.
43. McLennan N. F., Brennan P. M., McNeill A., et al., (2004) Prion protein accumulation and neuroprotection in hypoxic brain damage. Am. J. Pathol. 165, 227-235.
44. Meister A., (1974) The gamma-glutamyl cycle. Diseases associated with specific enzyme deficiencies. Ann. Intern. Med. 81, 247-253.
45. Milhavet O., and, Lehmann S., (2002) Oxidative stress and the prion protein in transmissible spongiform encephalopathies. Brain Res. Brain Res. Rev. 38, 328-339.
46. Millhauser G. L., (2004) Copper binding in the prion protein. Acc. Chem. Res. 37, 79-85.
47. Millhauser G. L., (2007) Copper and the prion protein: methods, structures, function, and disease. Annu. Rev. Phys. Chem. 58, 299-320.
48. Minich T., Riemer J., Schulz J. B., Wielinga P., Wijnholds J., and, Dringen R., (2006) The multidrug resistance protein 1 (Mrp1), but not Mrp5, mediates export of glutathione and glutathione disulfide from brain astrocytes. J. Neurochem. 97, 373-384.
49. Mitteregger G., Vosko M., Krebs B., Xiang W., Kohlmannsperger V., Nölting S., Hamann G. F., and, Kretzschmar H. A., (2007) The role of the octarepeat region in neuroprotective function of the cellular prion protein. Brain Pathol. 17, 174-183.
50. Miura T., Sasaki S., Toyama A., and, Takeuchi H., (2005) Copper reduction by the octapeptide repeat region of prion protein: pH dependence and implications in cellular copper uptake. Biochemistry 44, 8712-8720.
51. Morgenstern K., Hanson-Painton O., and, De Bault L., (1991) Cell surface gamma-glutamyl transpeptidase in live cultures. Anal. Biochem. 192, 165-172.
52. Mueller S. G., Trabesinger A. H., Boesiger P., and, Wieser H. G., (2001) Brain glutathione levels in patients with epilepsy measured by in vivo 1H-MRS. Neurology 57, 1422-1427.
53. Petrakis S., and, Sklaviadis T., (2006) Identification of proteins with high affinity for refolded and native PrPC. Proteomics 6, 6476-6484.
54. Pietri M., Caprini A., Mouillet-Richard S., Pradines E., Ermonval M., Grassi J., Kellermann O., and, Schneider B., (2006) Overstimulation of PrPC signaling pathways by prion peptide 106-126 causes oxidative injury of bioaminergic neuronal cells. J. Biol. Chem. 281, 28470-28479.
55. Prusiner S. B., (1998) Prions. Proc. Natl Acad. Sci. USA 95, 13363-13383.
56. Rachidi W., Vilette D., Guiraud P., Arlotto M., Riondel J., Laude H., Lehmann S., and, Favier A., (2003) Expression of prion protein increases cellular copper binding and antioxidant enzyme activities but not copper delivery. J. Biol. Chem. 278, 9064-9072.
57. Raeber A. J., Race R. E., Brandner S., et al., (1997) Astrocyte-specific expression of hamster prion protein (PrP) renders PrP knockout mice susceptible to hamster scrapie. EMBO J. 16, 6057-6065.
58. Rana S., and, Dringen R., (2007) Gap junction hemichannel-mediated release of glutathione from cultured rat astrocytes. Neurosci. Lett. 415, 45-48.
59. Rose E. M., Koo J. C., Antflick J. E., Ahmed S. M., Angers S., and, Hampson D. R., (2009) Glutamate transporter coupling to Na,K-ATPase. J. Neurosci. 29, 8143-8155.
60. Roucou X., Gains M., and, LeBlanc A. C., (2004) Neuroprotective functions of prion protein. J. Neurosci. Res. 75, 153-161.
61. Sagara J., Makino N., and, Bannai S., (1996) Glutathione efflux from cultured astrocytes. J. Neurochem. 66, 1876-1881.
62. Schulz J. B., Lindenau J., Seyfried J., and, Dichgans J., (2000) Glutathione, oxidative stress and neurodegeneration. Eur. J. Biochem. 267, 4904-4911.
63. Schurr A., Payne R. S., Miller J. J., and, Rigor B. M., (1997) Brain lactate is an obligatory aerobic energy substrate for functional recovery after hypoxia: further in vitro validation. J. Neurochem. 69, 423-426.
64. Shanker G., Allen J. W., Mutkus L. A., and, Aschner M., (2001) The uptake of cysteine in cultured primary astrocytes and neurons. Brain Res. 902, 156-163.
65. Sheldon A. L., González M. I., and, Robinson M. B., (2006) A carboxyl-terminal determinant of the neuronal glutamate transporter, EAAC1, is required for platelet-derived growth factor-dependent trafficking. J. Biol. Chem. 281, 4876-4886.
66. Shmerling D., Hegyi I., Fischer M., et al., (1998) Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions. Cell 93, 203-214.
67. Shyu W. C., Chen C. P., Saeki K., et al., (2005) Hypoglycemia enhances the expression of prion protein and heat-shock protein 70 in a mouse neuroblastoma cell line. J. Neurosci. Res. 80, 887-894.
68. Spudich A., Frigg R., Kilic E., Kilic U., Oesch B., Raeber A., Bassetti C. L., and, Hermann D. M., (2005) Aggravation of ischemic brain injury by prion protein deficiency: role of ERK-1/-2 and STAT-1. Neurobiol. Dis. 20, 442-449.
69. Stewart V. C., Stone R., Gegg M. E., Sharpe M. A., Hurst R. D., Clark J. B., and, Heales S. J., (2002) Preservation of extracellular glutathione by an astrocyte derived factor with properties comparable to extracellular superoxide dismutase. J. Neurochem. 83, 984-991.
70. Vana K., Zuber C., Nikles D., and, Weiss S., (2007) Novel aspects of prions, their receptor molecules, and innovative approaches for TSE therapy. Cell. Mol. Neurobiol. 27, 107-128.
71. Vanderberg R. J., (1998) Molecular pharmacology and physiology of glutamate transporters in the central nervous system. Clin. Exp. Pharmacol. Physiol. 25, 393-400.
72. Vassallo N., and, Herms J., (2003) Cellular prion protein function in copper homeostasis and redox signalling at the synapse. J. Neurochem. 86, 538-544.
73. Walz R., Amaral O. B., Rockenbach I. C., Roesler R., Izquierdo I., Cavalheiro E. A., Martins V. R., and, Brentani R. R., (1999) Increased sensitivity to seizures in mice lacking cellular prion protein. Epilepsia 40, 1679-1682.
74. Wang S., Cesca F., Loers G., Schweizer M., Buck F., Benfenati F., Schachner M., and, Kleene R., (2011) Synapsin I is an oligomannose-carrying glycoprotein, acts as an oligomannose-binding lectin, and promotes neurite outgrowth and neuronal survival when released via glia-derived exosomes. J. Neurosci. 31, 7275-7290.
75. Weis S., Haybaeck J., Dulay J. R., and, Llenos I. C., (2008) Expression of cellular prion protein (PrP(c)) in schizophrenia, bipolar disorder, and depression. J. Neural. Transm. 115, 761-771.
76. Weise J., Crome O., Sandau R., Schulz-Schaeffer W., Bähr M., and, Zerr I., (2004) Upregulation of cellular prion protein (PrPc) after focal cerebral ischemia and influence of lesion severity. Neurosci. Lett. 372, 146-150.
77. Weise J., Sandau R., Schwarting S., Crome O., Wrede A., Schulz-Schaeffer W., Zerr I., and, Bähr M., (2006) Deletion of cellular prion protein results in reduced Akt activation, enhanced postischemic caspase-3 activation, and exacerbation of ischemic brain injury. Stroke 37, 1296-1300.
78. Weise J., Doeppner T. R., Müller T., Wrede A., Schulz-Schaeffer W., Zerr I., Witte O. W., and, Bähr M., (2008) Overexpression of cellular prion protein alters postischemic Erk1/2 phosphorylation but not Akt phosphorylation and protects against focal cerebral ischemia. Restor. Neurol. Neurosci. 26, 57-64.
79. Weissmann C., and, Flechsig E., (2003) PrP knock-out and PrP transgenic mice in prion research. Br. Med. Bull. 66, 43-60.
80. Wille H., Michelitsch M. D., Guenebaut V., Supattapone S., Serban A., Cohen F. E., Agard D. A., and, Prusiner S. B., (2002) Structural studies of the scrapie prion protein by electron crystallography. Proc. Natl Acad. Sci. USA 99, 3563-3568.
81. Yang C. S., Chou S. T., Lin N. N., Liu L., Tsai P. J., Kuo J. S., and, Lai J. S., (1994) Determination of extracellular glutathione in rat brain by microdialysis and high-performance liquid chromatography with fluorescence detection. J. Chromatogr. B, Biomed. Appl. 661, 231-235.
82. Yudkoff M., Pleasure D., Cregar L., Lin Z. P., Nissim I., Stern J., and, Nissim I., (1990) Glutathione turnover in cultured astrocytes: studies with [15N]glutamate. J. Neurochem. 55, 137-145.
83. Zerangue N., and, Kavanaugh M. P., (1996) Interaction of L-cysteine with a human excitatory amino acid transporter. J. Physiol. (Lond.) 493, 419-423.