UC Santa Cruz

The research in this dissertation explores the bioactivity and biosynthesis of lipoxygenase-derived products from polyunsaturated fatty acids as well as drug discovery. The diseases that cause most of the mortality today are due to chronic inflammation, which is caused by the lack of a proper resolution phase. The pro-resolution molecules are oxylipins catalyzed by oxygenases and derived from fish oil. Dietary, genetic, and environmental effects have a role in altering these lipid signaling pathways and causing inflammation. This thesis examines how these molecules are made, their effects on resolving inflammation, and possible relations to disease. The first chapter investigates human 12-lipoxygenase metabolites from omega-6 docosapentaenoic acid as a promising novel anti-platelet for the treatment of the life-threatening complications of cardiovascular diseases. The second chapter quantifies oxyipins and cytokines in human blood as possible biomarkers for heart failure. The next chapter characterizes the Pseudomonas Aeruginosa lipoxygenase, reveals possible roles in biofilm formation and manipulation of host immune response, and discovers first in class selective inhibitors. Finally, the last chapter describes the resolution of inflammation and the biosynthesis of a class of specialized proresolving mediators, the maresins.