oxidants and antioxidants in biology - Oxygen Club of California

1-cysPeroxiredoxin as a lung antioxidant enzyme
A.B. FISHER, Y. MANEVICH, S.I. FEINSTEIN
Institute for Environmental Medicine, University of Pennsylvania Medical
Center, Philadelphia, PA 19104, USA.
Peroxiredoxins (Prx) are a recently described and widely distributed
family of peroxidases. Of the 6 mammalian isoforms, 5
use thioredoxin as the redox cofactor while 1-cysPrx uses GSH. 1-
cysPrx has a single conserved cysteine and forms a sulfenic acid as
the redox intermediate. The enzyme shows broad substrate specificity
for hydroperoxides ranging from H 2 O 2 to phosphatidylcholine
hydroperoxide with similar kinetic constant of approximately
2-5x 10 6 M -1 sec -1 . 1-cysPrx is widely expressed in mammalian
tissues and is especially enriched in lungs, brain, eye, and testes.
Exposure of rats or mice to 100% O 2 for 48-63 h resulted in an approximate
doubling of lung 1-cysPrx mRNA, protein, and activity
suggesting an anti-oxidant role for the enzyme. To test its role in
anti-oxidant defense, we used a lung epithelial cell line (H441) to
stably overexpress 1-cysPrx as a fusion protein with green fluorescent
protein. Overexpressing cells showed increased resistance to
Cu-ascorbate-generated oxidative stress with decreased accumulation
of lipid peroxides and less annexin V binding. In another lung
epithelial cell line (L2), antisense treatment reduced 1-cysPrx expression
and resulted in lipid peroxidation and cellular apoptosis as
indicated by increased annexin V binding and TUNEL assay.
These results indicate that 1-cysPrx can function as an antioxidant
enzyme and can protect cells from oxidant-mediated injury by oxidant
scavenging and reduction of peroxidized membrane phospholipids.
Refs.: Fisher, A.B. et al. JBC 274:21326, 1999. Chen, J-W. et al. JBC 276:
28421, 2000. Manevich, Y. et al. PNAS 99:11599, 2002. Pak, J-H. et al. JBC
277:49927, 2002
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