Hypocatalasemic fibroblasts accumulate hydrogen peroxide and display age-associated pathologies.
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.
Wood
Christopher S
CS
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Koepke
Jay I
JI
Teng
Hua
H
Boucher
Krissy K
KK
Katz
Sharon
S
Chang
Patrick
P
Terlecky
Laura J
LJ
Papanayotou
Irene
I
Walton
Paul A
PA
Terlecky
Stanley R
SR
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
D006861:Hydrogen Peroxide; D002374:Catalase; D001616:beta-Galactosidase