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.
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Hypocatalasemic fibroblasts show senescent-derived disorders.
“Actually, hypocatalasemic fibroblasts show senescent-derived disorders [54,55].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [55]
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- Authors
- Wood, C. S., Koepke, J. I., Teng, H., Boucher, K. K., Katz, S., Chang, P., Terlecky, L. J., Papanayotou, I., Walton, P. A., & Terlecky, S. R.
- Affiliations
- Wayne State University (US)
- Western University (CA)
- Corresponding author
- Terlecky, Stanley R.
- Venue
- Traffic
- Publisher
- Wiley
- Published
- 2005-11-09
- Volume
- 7
- Issue
- 1
- Pages
- 97-107
- ISSN
- 1398-9219 (ISSN-L)
- 1600-0854
- OpenAlex
- W1742842239
- Cited by
- 55
- References
- 56
- Citations by year
- 2024: 8 · 2023: 2 · 2022: 3 · 2021: 1 · 2018: 5 · 2017: 4 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 5 · 2012: 6
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Traffic (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p30es006639-15)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK056299, DK-56299)
- National Institute of Environmental Health Sciences (P-30-ES06639)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- hypocatalasemia, catalase, hydrogen peroxide accumulation, oxidative stress, human fibroblasts, peroxisomes, peroxisome biogenesis, protein damage, DNA damage, cellular senescence, age-related diseases, protein therapy
- MeSH terms
- Age Factors, beta-Galactosidase, Catalase, Fibroblasts, Humans, Hydrogen Peroxide, Metabolism, Inborn Errors, Cellular Senescence, Oxidative Stress, Peroxisomes, Cell Proliferation
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