Pharmacological enhancement of glutamate transport reduces excitotoxicity in vitro.
作者： Justin A. Beller , Gene G. Gurkoff , Robert F. Berman , Bruce G. Lyeth
DOI: 10.3233/RNN-2011-603
关键词:
摘要: Purpose Glutamate transporters are responsible for removing glutamate from the extracellular space and have potential to protect neurons excitotoxicity. In present study, effects of ceftriaxone (2R, 4R)-APDC (APDC) on protein expression GLAST GLT-1, rate uptake, neuroprotection were evaluated in a cell culture model Methods Mixed neuron/astrocyte cultures prepared 1 day old rat pups. Protein levels GLT-1 quantified using In-Cell Western techniques after acute or 5-day treatment with either APDC. uptake was measured Michaelis-Menten kinetics evaluate Neuronal death response 10-minute mM challenge following Results Five-day 100 μM significantly increased both 31.3% 47.5% above control, respectively, Vmax 29.3%, Km 117.9%, reduced neuronal 22.0% challenge. APDC 27.6%, 92.4%, transport 118.9%, decreased 36.8% Conclusions Chronic provided excitotoxicity while increasing uptake. These compounds may therapeutic chronic excitotoxic neurodegenerative diseases.
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sci-hub.se 参考文章(43)
Georgi Gegelashvili, Michael B. Robinson, Davide Trotti, Thomas Rauen, Regulation of glutamate transporters in health and disease Glial cell function. ,vol. 132, pp. 267- 286 ,(2001) , 10.1016/S0079-6123(01)32082-4
M Casado, A Bendahan, F Zafra, N C Danbolt, C Aragón, C Giménez, B I Kanner, Phosphorylation and modulation of brain glutamate transporters by protein kinase C. Journal of Biological Chemistry. ,vol. 268, pp. 27313- 27317 ,(1993) , 10.1016/S0021-9258(19)74251-3
Yoshikatsu Kanai, Craig P. Smith, Matthias A. Hediger, A new family of neurotransmitter transporters: the high-affinity glutamate transporters. The FASEB Journal. ,vol. 7, pp. 1450- 1459 ,(1993) , 10.1096/FASEBJ.7.15.7903261
J. Alfredo Méndez, Esther López-Bayghen, Fausto Rojas, María Elena Hernández, Arturo Ortega, Glutamate regulates Oct-2 DNA-binding activity through α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors in cultured chick Bergmann glia cells Journal of Neurochemistry. ,vol. 88, pp. 835- 843 ,(2004) , 10.1046/J.1471-4159.2003.02206.X
Dongni Yang, Robert W. Gereau, Group II metabotropic glutamate receptors inhibit cAMP-dependent protein kinase-mediated enhancement of tetrodotoxin-resistant sodium currents in mouse dorsal root ganglion neurons Neuroscience Letters. ,vol. 357, pp. 159- 162 ,(2004) , 10.1016/J.NEULET.2003.11.074
Anthony C. Vernon, Martin J. Croucher, David T. Dexter, Additive neuroprotection by metabotropic glutamate receptor subtype-selective ligands in a rat Parkinsonʼs model NeuroReport. ,vol. 19, pp. 475- 478 ,(2008) , 10.1097/WNR.0B013E3282F602DF
Bruce G. Lyeth, Qin-Zhi Gong, Shannon Shields, J.Paul Muizelaar, Robert F. Berman, Group I metabotropic glutamate antagonist reduces acute neuronal degeneration and behavioral deficits after traumatic brain injury in rats. Experimental Neurology. ,vol. 169, pp. 191- 199 ,(2001) , 10.1006/EXNR.2001.7643
Marike Zwienenberg, Qin-Zhi Gong, Robert F. Berman, J. Paul Muizelaar, Bruce G. Lyeth, The effect of groups II and III metabotropic glutamate receptor activation on neuronal injury in a rodent model of traumatic brain injury. Neurosurgery. ,vol. 48, pp. 1119- 1127 ,(2001) , 10.1097/00006123-200105000-00031
Seok-Geun Lee, Zhao-Zhong Su, Luni Emdad, Pankaj Gupta, Devanand Sarkar, Alejandra Borjabad, David J. Volsky, Paul B. Fisher, Mechanism of ceftriaxone induction of excitatory amino acid transporter-2 expression and glutamate uptake in primary human astrocytes Journal of Biological Chemistry. ,vol. 283, pp. 13116- 13123 ,(2008) , 10.1074/JBC.M707697200
Matthew L. Kelso, Nicole N. Scheff, Stephen W. Scheff, James R. Pauly, Melatonin and minocycline for combinatorial therapy to improve functional and histopathological deficits following traumatic brain injury Neuroscience Letters. ,vol. 488, pp. 60- 64 ,(2011) , 10.1016/J.NEULET.2010.11.003