skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Progeric effects of catalase inactivation in human cells

Abstract

Peroxisomes generate hydrogen peroxide, a reactive oxygen species, as part of their normal metabolism. A number of pathological situations exist in which the organelle's capacity to degrade the potentially toxic oxidant is compromised. It is the peroxidase, catalase, which largely determines the functional antioxidant capacity of the organelle, and it is this enzyme that is affected in aging, in certain diseases, and in response to exposure to specific chemical agents. To more tightly control the enzymatic activity of peroxisomal catalase and carefully document the effects of its impaired action on human cells, we employed the inhibitor 3-amino-1,2,4-triazole. We show that by chronically reducing catalase activity to approximately 38% of normal, cells respond in a dramatic manner, displaying a cascade of accelerated aging reactions. Hydrogen peroxide and related reactive oxygen species are produced, protein and DNA are oxidatively damaged, import into peroxisomes and organelle biogenesis is corrupted, and matrix metalloproteinases are hyper-secreted from cells. In addition, mitochondria are functionally impaired, losing their ability to maintain a membrane potential and synthesize reactive oxygen species themselves. These latter results suggest an important redox-regulated connection between the two organelle systems, a topic of considerable interest for future study.

Authors:
; ;  [1];  [2]
  1. Department of Pharmacology, Wayne State University School of Medicine, 540 E. Canfield Avenue, Detroit, Michigan, 48201 (United States)
  2. Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario (Canada)
Publication Date:
OSTI Identifier:
21144125
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 232; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2008.06.004; PII: S0041-008X(08)00253-6; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AGING; ANIMAL CELLS; ANTIOXIDANTS; CATALASE; DNA; HYDROGEN PEROXIDE; IODIDES; MEMBRANE PROTEINS; METABOLISM; MITOCHONDRIA; OXIDIZERS; TOXICITY; TRIAZOLES

Citation Formats

Koepke, Jay I, Wood, Christopher S, Terlecky, Laura J, Walton, Paul A, and Terlecky, Stanley R. Progeric effects of catalase inactivation in human cells. United States: N. p., 2008. Web. doi:10.1016/j.taap.2008.06.004.
Koepke, Jay I, Wood, Christopher S, Terlecky, Laura J, Walton, Paul A, & Terlecky, Stanley R. Progeric effects of catalase inactivation in human cells. United States. https://doi.org/10.1016/j.taap.2008.06.004
Koepke, Jay I, Wood, Christopher S, Terlecky, Laura J, Walton, Paul A, and Terlecky, Stanley R. 2008. "Progeric effects of catalase inactivation in human cells". United States. https://doi.org/10.1016/j.taap.2008.06.004.
@article{osti_21144125,
title = {Progeric effects of catalase inactivation in human cells},
author = {Koepke, Jay I and Wood, Christopher S and Terlecky, Laura J and Walton, Paul A and Terlecky, Stanley R.},
abstractNote = {Peroxisomes generate hydrogen peroxide, a reactive oxygen species, as part of their normal metabolism. A number of pathological situations exist in which the organelle's capacity to degrade the potentially toxic oxidant is compromised. It is the peroxidase, catalase, which largely determines the functional antioxidant capacity of the organelle, and it is this enzyme that is affected in aging, in certain diseases, and in response to exposure to specific chemical agents. To more tightly control the enzymatic activity of peroxisomal catalase and carefully document the effects of its impaired action on human cells, we employed the inhibitor 3-amino-1,2,4-triazole. We show that by chronically reducing catalase activity to approximately 38% of normal, cells respond in a dramatic manner, displaying a cascade of accelerated aging reactions. Hydrogen peroxide and related reactive oxygen species are produced, protein and DNA are oxidatively damaged, import into peroxisomes and organelle biogenesis is corrupted, and matrix metalloproteinases are hyper-secreted from cells. In addition, mitochondria are functionally impaired, losing their ability to maintain a membrane potential and synthesize reactive oxygen species themselves. These latter results suggest an important redox-regulated connection between the two organelle systems, a topic of considerable interest for future study.},
doi = {10.1016/j.taap.2008.06.004},
url = {https://www.osti.gov/biblio/21144125}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 232,
place = {United States},
year = {Wed Oct 01 00:00:00 EDT 2008},
month = {Wed Oct 01 00:00:00 EDT 2008}
}