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BDNF regulates GLAST and glutamine synthetase in mouse retinal Müller cells
Author(s) -
DAI MIN,
XIA XIAOBO,
XIONG SIQI
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22762
Subject(s) - glutamine synthetase , retinal , glutamine , microbiology and biotechnology , biology , chemistry , biochemistry , amino acid
This study investigated whether brain‐derived neurotrophic factor (BDNF) regulates the L‐glutamate/L‐aspartate transporter (GLAST) and glutamine synthetase (GS) in mouse retinal Müller cells (RMCs) under normal and hypoxic conditions. Mouse RMCs were treated with recombinant human BDNF (50, 75, 100, 125, or 150 ng/ml) for 24 h or underwent hypoxia induced by CoCl 2 (125 µM; 6, 12, 24, 48, or 72 h). An additional group underwent combined treatment with BDNF (100 ng/ml; 24, 48, 72, or 96 h) and CoCl 2 (125 µM/ml; 72 h). GLAST and GS mRNA and protein expression, L‐[3,4‐3H]‐glutamic acid uptake, and apoptosis were assessed. BDNF dose‐dependently up‐regulated GLAST and GS mRNA and protein and increased glutamate uptake. Similarly, in early‐stage CoCl 2 ‐induced hypoxia, GLAST and GS were up‐regulated and glutamate uptake increased, but these decreased over time. BDNF also up‐regulated GLAST and GS and increased glutamate uptake when RMCs under CoCl 2 induced hypoxic condition. However, BDNF treatment 24 h before CoCl 2 had no effect on GLAST or GS expression. CoCl 2 alone or combined with BDNF did not induce apoptosis. Hypoxia rapidly increased GLAST and GS expressions. This effect was transient, perhaps due to compensatory mechanisms that reduce GLAST and GS by 72 h. BDNF can up‐regulate GLAST and GS and increase glutamate uptake during hypoxia, and these functions may underlie its neuroprotective effects. J. Cell. Physiol. 227: 596–603, 2012. © 2011 Wiley Periodicals, Inc.