Reactive oxygen species (ROS) are well known to be fundamental for macrophages to kill invasive microorganisms. Moreover, they have an important role in regulating signal transduction pathways, gene expression and differentiation. Besides NADPH oxidase, mitochondria are gaining increasing relevance as a source of ROS in immune cells, although the exact sites of formation are only partially elucidated. Monoamine oxidase (MAO) is a relevant source of H2O2 in mitochondria, generated by oxidative deamination of biogenic amines. Since this enzyme has been scarcely characterized in phagocytic cells, we aimed at clarifying whether it plays a role in the differentiation and activation of macrophages. Indeed, on the basis of our preliminary data, we hypothesize that oxidative stress induced by MAO activity may play a crucial role in excessive inflammation and tissue damage in sepsis, the leading cause of death in intensive care units in high-income countries. Thus, we are currently investigating whether clinical-grade monoamine oxidase inhibitors can be viable candidates in the treatment of sepsis.
Selected PublicationsSorato E, Menazza S, Zulian A, Sabatelli P, Gualandi F, Merlini L, Bonaldo P, Canton M, Bernardi P, Di Lisa F.. 2014. Monoamine oxidase inhibition prevents mitochondrial dysfunction and apoptosis in myoblasts from patients with collagen VI myopathies. Free Radic Biol Med, 10, 40-47.
Canton M, Menazza S, Sheeran F L, Polverino De Laureto P, Di Lisa F, And Pepe S . 2011. Oxidation of myofibrillar proteins in human heart failure. J Am Coll Cardiol, vol. 57 (3); p. 300-309, ISSN: 0735-1097
Menazza S, Blaauw B, Tiepolo T, Toniolo L, Braghetta P, Spolaore B, Reggiani C, Di Lisa F, Bonaldo P, Canton M. . 2010. Oxidative stress by monoamine oxidases is causally involved in myofiber damage in muscular dystrophy. Hum Mol Genet, vol. 19; p. 4207-4215
Caffieri S, Di Lisa F, Bolesani F, Facco M, Semenzato G, Dall'Acqua F, Canton M. . 2007. The mitochondrial effects of novel apoptogenic molecules generated by psoralen photolysis as a crucial mechanism in PUVA therapy. Blood , 109 (11), 4988-94.
Canton M, Skyschally A, Menabo R, Boengler K, Gres P, Schulz R, Haude M, Erbel R, Di Lisa F, Heusch G. . 2006. Oxidative modification of tropomyosin and myocardial dysfunction following coronary microembolization. Eur Heart J , 27 (7), 875-81
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