Increased adenine nucleotide translocator 1 in reactive astrocytes facilitates glutamate transport

被引:23
作者
Buck, CR
Jurynec, MJ
Gupta, DK
Law, AKT
Bilger, J
Wallace, DC
McKeon, RJ
机构
[1] Oridis Biomed, A-8010 Graz, Austria
[2] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA
[3] Emory Univ, Dept Physiol, Atlanta, GA 30322 USA
[4] Emory Univ, Ctr Mol Med, Atlanta, GA 30322 USA
[5] Emory Univ, Dept Cell Biol, Atlanta, GA 30322 USA
关键词
glial scar; neuroprotection; mitochondria; transforming growth factor-beta 1 (TGF-beta 1); CNS injury; differential display PCR;
D O I
10.1016/S0014-4886(03)00043-8
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
A hallmark of central nervous system (CNS) pathology is reactive astrocyte production of the chronic glial scar that is inhibitory to neuronal regeneration. The reactive astrocyte response is complex; these cells also produce neurotrophic factors and are responsible for removal of extracellular glutamate, the excitatory neurotransmitter that rises to neurotoxic levels in injury and disease. To identify genes expressed by reactive astrocytes, we employed an in vivo model of the glial scar and differential display PCR and found an increase in the level of Aral, a mitochondrial ATP/ADP exchanger that facilitates the flux of ATP out of the mitochondria. Ant1 expression in reactive astrocytes is regulated by transforming growth factor-beta1, a pluripotent CNS injury-induced cytokine. The significance of increased Ant1 is evident from the observation that glutamate uptake is significantly decreased in astrocytes from Ant1 null mutant mice while a specific Ant inhibitor reduces glutamate uptake in wild-type astrocytes. Thus, the astrocytic response to CNS injury includes an apparent increase in energy mobilization capacity by Ant1 that contributes to neuroprotective, energy-dependent glutamate uptake. (C) 2003 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:149 / 158
页数:10
相关论文
共 51 条
[1]  
Asher RA, 2000, J NEUROSCI, V20, P2427
[2]   EFFECTS OF TRANSFORMING GROWTH FACTOR-BETA-1 ON THE EXTRACELLULAR-MATRIX AND CYTOSKELETON OF CULTURED ASTROCYTES [J].
BAGHDASSARIAN, D ;
TORUDELBAUFFE, D ;
GAVARET, JM ;
PIERRE, M .
GLIA, 1993, 7 (03) :193-202
[3]   ASTROGLIAL RESPONSE TO STABBING - IMMUNOFLUORESCENCE STUDIES WITH ANTIBODIES TO ASTROCYTE-SPECIFIC PROTEIN (GFA) IN MAMMALIAN AND SUB-MAMMALIAN VERTEBRATES [J].
BIGNAMI, A ;
DAHL, D .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 1976, 2 (02) :99-110
[4]  
Blanc EM, 1998, GLIA, V22, P149, DOI 10.1002/(SICI)1098-1136(199802)22:2<149::AID-GLIA6>3.0.CO
[5]  
2-2
[6]   Neurite outgrowth inhibitor of gliotic brain tissue. Mode of action and cellular localization, studied with specific monoclonal antibodies [J].
Bovolenta, P ;
FernaudEspinosa, I ;
MendezOtero, R ;
NietoSampedro, M .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1997, 9 (05) :977-989
[7]   Up-regulation of a serine protease inhibitor in astrocytes mediates the neuroprotective activity of transforming growth factor β1 [J].
Buisson, A ;
Nicole, O ;
Docagne, F ;
Sartelet, H ;
MacKenzie, ET ;
Vivien, D .
FASEB JOURNAL, 1998, 12 (15) :1683-1691
[8]   Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice [J].
Bush, TG ;
Puvanachandra, N ;
Horner, CH ;
Polito, A ;
Ostenfeld, T ;
Svendsen, CN ;
Mucke, L ;
Johnson, MH ;
Sofroniew, MV .
NEURON, 1999, 23 (02) :297-308
[9]   Robust regeneration of adult sensory axons in degenerating white matter of the adult rat spinal cord [J].
Davies, SJA ;
Goucher, DR ;
Doller, C ;
Silver, J .
JOURNAL OF NEUROSCIENCE, 1999, 19 (14) :5810-5822
[10]   Transcription of the adenine nucleotide translocase isoforms in various types of tissues in the rat [J].
Dörner, A ;
Olesch, M ;
Giessen, S ;
Pauschinger, M ;
Schultheiss, HP .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1999, 1417 (01) :16-24