N-acetylcysteine, but not methionine or 2-oxothiazolidine-4-carboxylate, serves as cysteine donor for the synthesis of glutathione in cultured neurons derived from embryonal rat brain

The ability of neurons to metabolize sulfur-containing compounds to cysteine was investigated using as indicator the glutathione content in neuron-rich primary cultures derived from the brains of embryonal rats. The glutathione content of these cultures was doubled during a 4-h incubation in a minimal medium containing cysteine, glutamine and glycine. In contrast, absence of cysteine or replacement of cysteine by methionine or 2-oxothiazolidine-4-carboxylate failed to increase the glutathione content of cultured neurons. Besides cysteine, N-acetylcysteine (NAC) also caused in the millimolar range, a concentration-dependent increase in the neuronal glutathione content during a 4-h incubation. These data suggest that neurons in culture, contain an acylase activity which allows them to generate from extracellular NAC as precursor intracellular cysteine in concentrations sufficient for glutathione synthesis. In contrast, generation of cysteine from 2-oxothiazolidine-4-carboxylate by the reaction of 5-oxoprolinase or from methionine by the transsulfuration pathway appears not to take place in these cultured neurons. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.