Differential induction of glutathione S-transferase in rat aorta versus liver.
Polycyclic aromatic hydrocarbons, cigarette smoke components that induce atherosclerosis in animals, require metabolic biotransformation to electrophilic intermediates to exhibit atherogenic effects. The formation of reactive metabolites depends on both rates of cytochrome P450-catalyzed oxidation and rates of detoxification through conjugation with glutathione. Thus, changes in the activity of glutathione S-transferase in vascular tissue could affect the risk of polycyclic aromatic hydrocarbon-induced atherogenesis. We compared the effects of several exogenous chemicals on levels of glutathione S-transferase in aorta and liver. Male Wistar rats were treated with 3-methylcholanthrene, a polycyclic aromatic hydrocarbon, phenobarbital and butylated hydroxytoluene, an antioxidant known to have anti-atherogenic properties. In control animals, glutathione S-transferase activity was about 20-fold greater in liver than in aorta. Subunit expression was tissue specific. GST-Yp, for example, was the most abundant subunit in aorta but was undetectable in liver. In contrast, GST-Ya was barely detectable in aorta but was abundant in liver. Each of the xenobiotics caused induction of glutathione S-transferase but the extent of induction was greater in liver than in aorta. Phenobarbital, for example, caused 300% induction in liver but only 70% induction in aorta. By western blot analysis, differences in amounts of enzyme subunits corresponded to changes in enzyme activity. Thus, exogenous chemicals differentially regulate levels of glutathione S-transferase in the aorta and liver.
Kashfi
K
K
Division of Digestive Diseases, New York Hospital-Cornell Medical Center, NY 10021.
Rimarachin
J A
JA
Weksler
B B
BB
Dannenberg
A J
AJ
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology*; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D004790:Enzyme Induction; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000737:chemistry; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D002084:Butylated Hydroxytoluene; D008748:Methylcholanthrene; D005982:Glutathione Transferase; D010634:Phenobarbital