DIFFERENCES IN THE GLUTATHIONE SYSTEM OF CULTURED AORTIC SMOOTH-MUSCLE CELLS FROM YOUNG AND AGED RATS

We studied the relation between the glutathione (GSH) system and cell proliferation in a model of smooth muscle cells (SMC) derived from the thoracic aorta of 4-6-week-old (young) and 15-month-old (aged) rats. SMC from aged rats showed greater levels of total non-protein thiol co mpounds (T-SH), increased glutathione transferase (GST) and increased glutathione reductase (GSSG-Red) activities compared with cells from y oung rats. These changes were associated with an increased proliferati on rate of SMC from aged rats. To evaluate the role of GSH on cell pro liferation better, a specific inhibitor of gamma-glutamyl-cystein synt hetase, DL-buthionine-SR-sulphoximine (BSO) was used. BSO showed a dos e-dependent inhibition of cell growth, with an IC50 of 10(-4) M, after 48-72 h of incubation. Removal of BSO restored cell growth, further s uggesting a link between GSH levels and vascular cell proliferation. T he inhibitory effect of BSO was about two times greater on SMC from yo ung than on SMC from aged rats. BSO showed 56% inhibition on the proli feration of SMC from young rats and 32% inhibition on SMC from aged ra ts (10(-4) M, 72 h of incubation). A parallel reduction of GSH levels of 38% and 19% for SMC from young and aged rats, respectively, was obs erved, suggesting that age-related factors may influence the involveme nt of GSH system in cell proliferation.