ALPHA-LIPOIC ACID INCREASES INTRACELLULAR GLUTATHIONE IN A HUMAN T-LYMPHOCYTE JURKAT CELL-LINE

The addition of exogenous a-lipoic acid to cellular medium causes a rapid increase of intracellular unbound thiols in Jurkat cells, a human T-lymphocyte cell line. The rise of cellular thiols is a result of the cellular uptake and reduction of lipoic acid to dihydrolipoic acid and a rise in intracellular glutathione. Although the level of dihydrolipoic acid is 100-fold lower than glutathione, the cellular concentration of dihydrolipoic acid might be responsible for the modulation of total cellular thiol levels. Rises in glutathione correlate with the levels of intracellular dihydrolipoic acid (p<.01). This increase in glutathione is not the result of expression of new proteins like gamma-glutamylcysteine synthetase, since the rise in glutathione was not inhibited by cycloheximide, a protein synthesis inhibitor. Lipoic acid administration is therefore a potential therapeutic agent in an array of diseases with glutathione anomalies including HIV infection. (C) 1995 Academic Press, Inc.