DIFFERENTIAL INDUCTION OF GLUTATHIONE-S-TRANSFERASE IN RAT AORTA VERSUS LIVER

Polycyclic aromatic hydrocarbons, cigarette smoke components that indu ce atherosclerosis in animals, require metabolic biotransformation to electrophilic intermediates to exhibit atherogenic effects. The format ion of reactive metabolites depends on both rates of cytochrome P450-c atalyzed oxidation and rates of detoxification through conjugation wit h glutathione. Thus, changes in the activity of glutathione S-transfer ase in vascular tissue could affect the risk of polycyclic aromatic hy drocarbon-induced atherogenesis. We compared the effects of several ex ogenous chemicals on levels of glutathione S-transferase in aorta and liver. Male Wistar rats were treated with 3-methylcholanthrene, a poly cyclic aromatic hydrocarbon, phenobarbital and butylated hydroxytoluen e, an antioxidant known to have anti-atherogenic properties. In contro l animals, glutathione S-transferase activity was about 20-fold greate r in liver than in aorta. Subunit expression was tissue specific. GST- Yp, for example, was the most abundant subunit in aorta but was undete ctable in liver. In contrast, GST-Ya was barely detectable in aorta bu t was abundant in liver. Each of the xenobiotics caused induction of g lutathione S-transferase but the extent of induction was greater in li ver than in aorta. Phenobarbital, for example, caused 300% induction i n liver but only 70% induction in aorta. By western blot analysis, dif ferences in amounts of enzyme subunits corresponded to changes in enzy me activity. Thus, exogenous chemicals differentially regulate levels of glutathione S-transferase in the aorta and liver.