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Upregulation of the glutamine transporter through transactivation mediated by camp/protein kinase a signals toward exacerbation of vulnerability to oxidative stress in rat neocortical astrocytes
Author(s) -
Ogura Masato,
Taniura Hideo,
Nakamichi Noritaka,
Yoneda Yukio
Publication year - 2007
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.21031
Subject(s) - forskolin , protein kinase a , biology , activator (genetics) , adenylyl cyclase , microbiology and biotechnology , astrocyte , kinase , biochemistry , signal transduction , stimulation , endocrinology , central nervous system , gene
In the present study, we have evaluated the possible functionality in astrocytes of the glutamine (Gln) transporter (GlnT) known to predominate in neurons for the neurotransmitter pool of glutamate. Sustained exposure to the adenylyl cyclase activator forskolin for 24 h led to a significant increase in mRNA expression of GlnT among different membrane transporters capable of transporting Gln, with an increase in [ 3 H]Gln accumulation sensitive to a system A transporter inhibitor, in cultured rat neocortical astrocytes, but not neurons. Forskolin drastically stimulated GlnT promoter activity in a manner sensitive to a protein kinase A (PKA) inhibitor in rat astrocytic C6 glioma cells, while deletion mutation analysis revealed that the stimulation was mediated by a cAMP responsive element (CRE)/activator protein‐1 (AP‐1) like site located on GlnT gene promoter. Forskolin drastically stimulated the promoter activity in a fashion sensitive to a PKA inhibitor in C6 glioma cells transfected with a CRE or AP‐1 reporter plasmid, in association with the phosphorylation of CRE binding protein on serine133. Transient overexpression of GlnT significantly exacerbated the cytotoxicity of hydrogen peroxide in cultured astrocytes. These results suggest that GlnT expression is upregulated by cAMP/PKA signals for subsequent exacerbation of the vulnerability to oxidative stress in astrocytes. J. Cell. Physiol. 212: 375–385, 2007. © 2007 Wiley‐Liss, Inc.