Comparative Effects of Superoxide Anion and Hydrogen Peroxide on Microsomal and Cytosolic Glutathione S-Transferase Activities of Rat Liver

• Published in: Biological trace element research 2010-05, Vol.134 (2), p.203-211
• Main Authors: Letelier, María Eugenia, Molina-Berríos, Alfredo, Cortés-Troncoso, Juan, Jara-Sandoval, José A, Müller, Andrea, Aracena-Parks, Paula
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biotechnology; Cytosol - drug effects; Cytosol - enzymology; Cytosol - metabolism; Glutathione Transferase - metabolism; Hydrogen peroxide; Hydrogen Peroxide - pharmacology; Life Sciences; Liver - enzymology; Male; Microsomes, Liver - drug effects; Microsomes, Liver - enzymology; Microsomes, Liver - metabolism; Nutrition; Oncology; Oxidants - pharmacology; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Superoxides - pharmacology
• ISSN: 0163-4984; 1559-0720
• DOI: 10.1007/s12011-009-8461-3

Glutathione S-transferases (GSTs) are isoenzymes occurring in the cytoplasm and as integral membrane proteins. In addition to their role in drug metabolism by conjugating electrophilic and lipophilic compounds with glutathione (GSH), these enzymes display multiple functions in cells, including antioxidant action. It has been generalized that reactive oxygen species (ROS) inhibit cytosolic GSTs and activate microsomal GSTs; some evidence shows, however, that different ROS-generating systems can inhibit microsomal GST activity. We therefore tested the effect of Fe³⁺/ascorbate, another ROS-generating system, on cytosolic and microsomal GST activities from rat liver cytosol and microsomes, respectively, and compared it to that of hydrogen peroxide (H₂O₂). We found that, while both agents displayed similar inhibitory effects on cytosolic GST activity, they promoted opposite effects on microsomal GST activity. Using specific antioxidant enzymes, we corroborated that the effect of Fe³⁺/ascorbate involves generation of [graphic removed] without dismutation into H₂O₂. Since these ROS have physicochemical properties and redox potentials that are very distinct, their reactivity is different, and their oxidative action is likely to have different targets. We discuss how these properties are related with the oxidative potency of ROS, especially those of [graphic removed] and H₂O₂.