Chapter 3: Manganese Superoxide Dismutase

Highly reactive oxygen species (ROS) such as superoxide anion, O₂^•−, are formed in various locations within a cell and their generation can alter a variety of signaling cascades and impact numerous cellular processes such as proliferation, respiration and survival. The primary antioxidant, manganese-containing superoxide dismutase (MnSOD), is critical for mitochondrial dismutation of O₂^•−, with subsequent generation of hydrogen peroxide (H₂O₂) and modulation of cellular redox status. Genetically modified animals have identified MnSOD as essential for aerobic life and current experimental Cre-loxP strategies are furthering our knowledge of tissue specific contributions of the enzyme. Current knowledge about the transcriptional and post-translational regulation of MnSOD as well as recent studies of how these changes influence specific disease states are reviewed. For over 30 years the role of MnSOD in cancer has been extensively studied. First thought to act as a tumor suppressor, studies were aimed at overexpression in both in vitro and in vivo carcinogenesis models. Recent studies suggest oncogenic potential of the enzyme in a variety of tumors and discussions of this recently discovered paradox, as well as future experiments for improving prognosis, are reviewed.