Hypocatalasemic fibroblasts accumulate hydrogen peroxide and display age-associated pathologies

TY - JOUR

T1 - Hypocatalasemic fibroblasts accumulate hydrogen peroxide and display age-associated pathologies

AU - Wood, Christopher S.

AU - Koepke, Jay I.

AU - Teng, Hua

AU - Boucher, Krissy K.

AU - Katz, Sharon

AU - Chang, Patrick

AU - Terlecky, Laura J.

AU - Papanayotou, Irene

AU - Walton, Paul A.

AU - Terlecky, Stanley R.

PY - 2006/1

Y1 - 2006/1

N2 - 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.

AB - 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.

KW - Aging

KW - Catalase

KW - Human disease

KW - Peroxisome

KW - Protein traffic

KW - Protein transduction

KW - Reactive oxygen species

UR - https://www.scopus.com/pages/publications/33645526302

U2 - 10.1111/j.1600-0854.2005.00358.x

DO - 10.1111/j.1600-0854.2005.00358.x

M3 - Article

C2 - 16445690

SN - 1398-9219

VL - 7

SP - 97

EP - 107

JO - Traffic

JF - Traffic

IS - 1

ER -