Meeting Abstract

54.4  Tuesday, Jan. 6  Protection of elevated membrane PUFA contents by GPx4 in marine vertebrates GRIM, Jeffrey/M*; CROCKETT, Elizabeth/L; KRISKA, Tamas; HYNDMAN, Kelly/A; ALBERT, Girotti/W; Ohio University and MDI Biological Laboratory; Ohio University and MDI Biological Laboratory; Medical College of Wisconsin; Medical College of Georgia and MDI Biological Laboratory; Medical College of Wisconsin

Reactive oxygen species (ROS) are formed during aerobic metabolism. Animals depend on a suite of defense for protection against ROS-induced damage. Among antioxidant enzymes catalase (CAT) eliminates H2O2, a primary ROS, while glutathione peroxidase-4 (GPx4) detoxifies lipid hydroperoxides produced during lipid peroxidation. We hypothesize that basal marine vertebrates have high levels of both CAT and GPx4 in order to protect elevated and highly oxidizable PUFA contents of biological membranes. We compared CAT and GPx4 activities in livers of six basal vertebrate species (hagfish, lamprey, spiny dogfish shark, two teleost fishes, and newt) with the mouse. Most marine animals had greater GPx4 activity compared to mouse. Highest activities (p < 0.0001) were found in hagfish and killifish being 3 and 5 fold, respectively, relative to mouse. GPx4 protein levels were greatest in dogfish (3.5-fold) and killifish (4.5-fold) relative to mouse (p < 0.002). CAT activity was most robust in newt (mean 6-fold increase) compared with other groups (p < 0.0001). Contrary to our expectation that marine vertebrates would show enhanced activities of both CAT and GPx4, a weak negative trend was present between these antioxidant enzymes, although it failed to reach significance (p = 0.06). These data indicate that livers of basal marine vertebrates possess particularly high activities of GPx4, which should facilitate their capacity to protect PUFA in biological membranes. Supported by MDIBLs NIEHS Center for Membrane Toxicity Studies (P30 ES003828-20) and Stan and Judy Fund, and and OU SEA Award (SEA-08-39).