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Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression

Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression Reactive oxygen species are involved in many cellular metabolic and signalling processes 1 and are thought to have a role in disease, particularly in carcinogenesis and ageing 2 . We have generated mice with targeted inactivation of Prdx1, a member of the peroxiredoxin family of antioxidant enzymes 3 . Here we show that mice lacking Prdx1 are viable and fertile but have a shortened lifespan owing to the development beginning at about 9 months of severe haemolytic anaemia and several malignant cancers, both of which are also observed at increased frequency in heterozygotes. The haemolytic anaemia is characterized by an increase in erythrocyte reactive oxygen species, leading to protein oxidation, haemoglobin instability, Heinz body formation and decreased erythrocyte lifespan. The malignancies include lymphomas, sarcomas and carcinomas, and are frequently associated with loss of Prdx1 expression in heterozygotes, which suggests that this protein functions as a tumour suppressor. Prdx1-deficient fibroblasts show decreased proliferation and increased sensitivity to oxidative DNA damage, whereas Prdx1-null mice have abnormalities in numbers, phenotype and function of natural killer cells. Our results implicate Prdx1 as an important defence against oxidants in ageing mice. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Springer Journals

Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression

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References (41)

Publisher
Springer Journals
Copyright
Copyright © 2003 by Macmillan Magazines Ltd.
Subject
Science, Humanities and Social Sciences, multidisciplinary; Science, Humanities and Social Sciences, multidisciplinary; Science, multidisciplinary
ISSN
0028-0836
eISSN
1476-4687
DOI
10.1038/nature01819
Publisher site
See Article on Publisher Site

Abstract

Reactive oxygen species are involved in many cellular metabolic and signalling processes 1 and are thought to have a role in disease, particularly in carcinogenesis and ageing 2 . We have generated mice with targeted inactivation of Prdx1, a member of the peroxiredoxin family of antioxidant enzymes 3 . Here we show that mice lacking Prdx1 are viable and fertile but have a shortened lifespan owing to the development beginning at about 9 months of severe haemolytic anaemia and several malignant cancers, both of which are also observed at increased frequency in heterozygotes. The haemolytic anaemia is characterized by an increase in erythrocyte reactive oxygen species, leading to protein oxidation, haemoglobin instability, Heinz body formation and decreased erythrocyte lifespan. The malignancies include lymphomas, sarcomas and carcinomas, and are frequently associated with loss of Prdx1 expression in heterozygotes, which suggests that this protein functions as a tumour suppressor. Prdx1-deficient fibroblasts show decreased proliferation and increased sensitivity to oxidative DNA damage, whereas Prdx1-null mice have abnormalities in numbers, phenotype and function of natural killer cells. Our results implicate Prdx1 as an important defence against oxidants in ageing mice.

Journal

Nature – Springer Journals

Published: Jul 31, 2003

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