N-Acetylcysteine,

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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

Ralf DringenA and Bernd Hamprecht

Physiologisch-chemisches Institut der Universität, Hoppe-Seyler-

Strasse 4, D-72076 Tübingen, Germany

A Corresponding author. Tel.: +49 7071 2973334; fax: +49 7071 295360;

e-mail: ralf.dringen@...

Manuscript received 16 October 1998 Revised 2 November 1998 Accepted

2 November 1998;

Abstract

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.

, but not methionine or 2-oxothiazolidine-4-carboxylate, serves as

cysteine donor for the synthesis of glutathione in cultured neurons