Inactivation of mammalian brain glutamine synthetase by oxygen radicals

Oxygen free radicals have been implicated in ischemic-reperfusion injury to the central nervous system. Ischemic injury to tissue is exacerbated in the presence of the excitatory neurotransmitter, glutamate. Glutamine synthetase is responsible for the conversion of glutamate to its non-toxic metabolite, glutamine, in the CNS. The present paper presents evidence for the inactivation of brain glutamine synthetase by oxygen radicals in vitro and in vivo, and suggests that such a mechanism may underlie the exacerbation of tissue injury in the reperfusion which follows an ischemic insult.