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 sur vival of neural cells and tissues, raising hopes for its therapeutic potent ial in degenerative disorders of the CNS. Here we examine the effect of bFG F on the expression of glutamine synthetase, a key enzyme in the detoxifica tion of the neurotransmitter glutamate. Expression of this enzyme is regula ted by systemic glucocorticoids and, in chick neural retina tissue, is rest ricted to Muller glial cells. We report that exogenous supply of bFGF to re tinal explants inhibits hormonal induction of glutamine synthetase expressi on. This inhibition appears to be mediated by the c-Jun protein which accum ulated, in response to bFGF, exclusively in Muller glial cells. Ischemic co nditions, which reportedly stimulate the release of endogenous bFGF, also l ed to an increase in c-Jun protein and a decline in glutamine synthetase ex pression. This decline could be competitively prevented by a soluble fibrob last growth factor receptor but not by a soluble epidermal growth factor re ceptor. The finding that endogenous release of bFGF or its exogenous supply down-regulates glutamine synthetase expression suggests that in addition t o its reported neuroprotective effect, bFGF may exacerbate glutamate mediat ed neurotoxicity through direct down-regulation of glutamine synthetase.