TAURINE SYNTHESIS AND CYSTEINE METABOLISM IN CULTURED RAT ASTROCYTES - EFFECTS OF HYPEROSMOTIC EXPOSURE

We investigated mechanisms controlling taurine synthesis in cultured r at cerebral astrocytes. The mean +/- SE rate of taurine synthesis from extracellular cysteine was 21.2 +/- 2.0 pmol . mg protein(-1) . min(- 1), whereas taurine degradation was <1.3% of this rate. Eliminating ce llular glutathione and inhibiting glutathione biosynthesis increased t aurine synthesis from extracellular cysteine by 39%. In cell homogenat es, cysteine dioxygenase (CDO) and cysteine-sulfinate decarboxylase ac tivities were 2.4 +/- 0.2 and 8.3 +/- 2.8 . nmol . mg protein(-1) min( -1), respectively. CDO activity was strongly dependent on cysteine con centration over physiological and pathophysiological ranges of intrace llular cysteine concentration. Growth in hyperosmotic medium caused a greater increase in culture medium taurine content than that measured from cells in isosmotic growth medium. Hyperosmotic treatment transien tly increased the rate of cysteine accumulation and cellular cysteine and glutathione contents but had no effect on the synthesis rate of ta urine from extracellular cysteine. Thus cysteine is accumulated and th en metabolized to taurine through CDO, whose activity depends on the i ntracellular cysteine concentration and appears to be rate limiting fo r taurine synthesis. Hyperosmotic exposure increases net taurine produ ction yet has no effect on taurine synthesis from exogenously applied cysteine. Availability of substrate from intracellular pools must cont ribute to maintenance of high intracellular taurine during hyperosmoti c exposure.