EFFECTS OF ALPHA-LIPOIC ACID AND DIHYDROLIPOIC ACID ON EXPRESSION OF PROTOONCOGENE C-FOS

The transcription factor AP-1 is an important human mediator of the cellular response to serum, growth factors, and phorbol esters such as 12-O-tetradecanoylphorbol-13 acetate (TPA). The AP-1 complex consists of distinct protein heterodimers encoded by the proto-oncogene c-fos and c-jun mRNA whose gene expression can be induced by TPA, cyclic AMP and growth factors. Recent findings suggest an involvement of reactive oxygen species in the pathway of TPA and protein kinase C leading to expression of c-fos and c-jun mRNA. To investigate the role of reactive oxygen species we studied the effects of alpha-lipoic acid and dihydrolipoic acid (natural thiol antioxidants) on the expression of c-fos mRNA in human Jurkat T cells. When cells were preincubated with dihydrolipoic acid (0.2 mM) the expression of c-fos mRNA was suppressed at 30 min after stimulation of TPA (0.5 mu M) whereas in the case of preincubation of alpha-lipoic acid (0.2 mu M), the expression was enhanced at 30 min. These studies support the idea that superoxide anion radical plays a role in the expression of c-fos mRNA. (C) 1994 Academic Press, Inc.