title: Hypocatalasemic fibroblasts accumulate hydrogen peroxide and display age-associated pathologies.
abstract: Human epidemiological studies point to an association of hypocatalasemia and an increased risk of age-related disease. Unfortunately, the cellular and molecular manifestations of hypocatalasemia are only poorly understood. In this analysis, we have extensively characterized hypocatalasemic human fibroblasts and report that they amass hydrogen peroxide and are oxidatively damaged. Protein and DNA alike are affected, as are functioning and biogenesis of peroxisomes - the subcellular organelles which normally house catalase. Despite these pathologies and their relative inability to grow, the cells do not appear to be intrinsically senescent. With the goal of restoring oxidative balance and perhaps reversing some of the accumulated damage to critical cellular components, we transduced hypocatalasemic fibroblasts with a form of catalase specifically designed to efficiently traffic to peroxisomes. We show the strategy is extremely effective, with dramatic reductions seen in cellular hydrogen peroxide levels. Future longitudinal studies aimed at examining the effects of a more continuous and long-term protein therapy may now commence.
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Wood
authors.forename: Jay I
authors.initials: JI
authors.lastname: Koepke
authors.forename: Hua
authors.initials: H
authors.lastname: Teng
authors.forename: Krissy K
authors.initials: KK
authors.lastname: Boucher
authors.forename: Sharon
authors.initials: S
authors.lastname: Katz
authors.forename: Patrick
authors.initials: P
authors.lastname: Chang
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Terlecky
authors.forename: Irene
authors.initials: I
authors.lastname: Papanayotou
authors.forename: Paul A
authors.initials: PA
authors.lastname: Walton
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Terlecky
mesh_terms: D000367:Age Factors; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000502:physiology*; D005347:Fibroblasts / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008661:Metabolism, Inborn Errors / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D020675:Peroxisomes / Q000201:enzymology / Q000502:physiology; D001616:beta-Galactosidase / Q000032:analysis
chemical_list: D006861:Hydrogen Peroxide; D002374:Catalase; D001616:beta-Galactosidase