Basic fibroblast growth factor: a potential inhibitor of glutamine synthetase expression in injured neural tissue.
Basic fibroblast growth factor (bFGF) was recently shown to promote the survival of neural cells and tissues, raising hopes for its therapeutic potential in degenerative disorders of the CNS. Here we examine the effect of bFGF on the expression of glutamine synthetase, a key enzyme in the detoxification of the neurotransmitter glutamate. Expression of this enzyme is regulated by systemic glucocorticoids and, in chick neural retina tissue, is restricted to Müller glial cells. We report that exogenous supply of bFGF to retinal explants inhibits hormonal induction of glutamine synthetase expression. This inhibition appears to be mediated by the c-Jun protein which accumulated, in response to bFGF, exclusively in Müller glial cells. Ischemic conditions, which reportedly stimulate the release of endogenous bFGF, also led to an increase in c-Jun protein and a decline in glutamine synthetase expression. This decline could be competitively prevented by a soluble fibroblast growth factor receptor but not by a soluble epidermal growth factor receptor. The finding that endogenous release of bFGF or its exogenous supply down-regulates glutamine synthetase expression suggests that in addition to its reported neuroprotective effect, bFGF may exacerbate glutamate mediated neurotoxicity through direct down-regulation of glutamine synthetase.
Kruchkova
Y
Y
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Ben-Dror
I
I
Herschkovitz
A
A
David
M
M
Yayon
A
A
Vardimon
L
L
D000818:Animals; D002642:Chick Embryo; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005974:Glutamate-Ammonia Ligase / Q000235:genetics*; D007511:Ischemia / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000201:enzymology*
D016755:Proto-Oncogene Proteins c-jun; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D005974:Glutamate-Ammonia Ligase