Reversing the Inactivation of Peroxiredoxins Caused by Cysteine Sulfinic Acid Formation

Woo, Hyun Ae; Chae, Ho Zoon; Hwang, Sung Chul; Yang, Kap Seok; Kang, Sang Won; Kim, Kanghwa; Rhee, Sue Goo

doi:10.1126/science.1080273

Cited by 512 publications

(368 citation statements)

References 25 publications

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“…During catalysis, Prx I is inactivated by oxidation of the active site cysteine to cysteine sulfinic acid, 33 a modification which is reversible upon removal of H 2 O 2 . 34 The modification of Prx I that we observed in 2-DE gel analysis of APIT-treated cells resembles that described for the oxidized and inactivated Prx I, 33 indicating that APIT inactivates this detoxification system. Previously, overexpression of both Prx I and Prx II has been shown to render cells resistant to H 2 O 2 -induced apoptosis.…”

Section: Discussionsupporting

confidence: 67%

Hydrogen peroxide produced by Aplysia ink toxin kills tumor cells independent of apoptosis via peroxiredoxin I sensitive pathways

et al. 2004

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Marine snails of the genus Aplysia possess numerous bioactive substances. We have purified a 60 kDa protein, APIT (Aplysia punctata ink toxin), from the defensive ink of A. punctata that triggers cell death with profound tumor specificity. Tumor cell death induced by APIT is independent of apoptosis but is characterized by the rapid loss of metabolic activity, membrane permeabilization, and shrinkage of nuclei. Proteome analysis of APIT-treated tumor cells indicated a modification of peroxiredoxin I, a cytoplasmic peroxidase involved in the detoxification of peroxides. Interestingly, knockdown of peroxiredoxin I expression by RNA interference sensitized cells for APIT-induced cell death. APIT induced the death of tumor cells via the enzymatic production of H 2 O 2 and catalase completely blocked APITs' activity. Our data suggest that H 2 O 2 induced stress and the modulation of peroxiredoxins might be a promising approach for tumor therapy.

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Section: Discussionsupporting

confidence: 67%

Hydrogen peroxide produced by Aplysia ink toxin kills tumor cells independent of apoptosis via peroxiredoxin I sensitive pathways

et al. 2004

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“…Alternatively, these spots may represent different degrees of oxidized cysteines as hyperoxidized proteins often exhibit lower pI values than their nonoxidized counterparts, as exemplified with hyperoxidized Cys (sulfinic and sulfonic acids) of peroxiredoxin. 30 Fig. 4.…”

Section: Resultsmentioning

confidence: 99%

Inactivation of oxidized andS-nitrosylated mitochondrial proteins in alcoholic fatty liver of rats

et al. 2006

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Increased oxidative/nitrosative stress is a major contributing factor to alcohol-mediated mitochondrial dysfunction. However, which mitochondrial proteins are oxidatively modified under alcohol-induced oxidative/nitrosative stress is poorly understood. The aim of this study was to systematically investigate oxidized and/or S-nitrosylated mitochondrial proteins and to use a biotin-N-maleimide probe to evaluate their inactivation in alcoholic fatty livers of rats. Binge or chronic alcohol exposure significantly elevated nitric oxide, inducible nitric oxide synthase, and ethanol-inducible CYP2E1. The biotin-N-maleimide-labeled oxidized and/or S-nitrosylated mitochondrial proteins from pair-fed controls or alcohol-fed rat livers were subsequently purified with streptavidin-agarose. The overall patterns of oxidized and/or S-nitrosylated proteins resolved by 2-dimensional polyacrylamide gel electrophoresis were very similar in the chronic and binge alcohol treatment groups. Seventy-nine proteins that displayed differential spot intensities from those of control rats were identified by mass spectrometry. These include mitochondrial aldehyde dehydrogenase 2 (ALDH2), ATP synthase, acyl-CoA dehydrogenase, 3-ketoacyl-CoA thiolase, and many proteins involved in chaperone activity, mitochondrial electron transfer, and ion transport. The activity of 3-ketoacyl-CoA thiolase involved in mitochondrial ␤-oxidation of fatty acids was significantly inhibited in alcohol-exposed rat livers, consistent with hepatic fat accumulation, as determined by biochemical and histological analyses. Measurement of activity and immunoblot results showed that ALDH2 and ATP synthase were also inhibited through oxidative modification of their cysteine or tyrosine residues in alcoholic fatty livers of rats. In conclusion, our results help to explain the underlying mechanism for mitochondrial dysfunction and increased susceptibility to alcohol-mediated liver damage. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

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“…9 Recent studies have shown that the active site cysteine of PRDXs is selectively oxidized to cysteine sulfinic acid, leading to inactivation of peroxidase activity, and the sulfinic form of PRDX is rapidly reduced to the catalytically active thiol form. 10,11 It appears that the cell's ability to reduce protein sulfinic acid serves as a mechanism to repair damaged proteins or represents a new type of cyclic modification regulating the functions of various proteins.…”

Section: Introductionmentioning

confidence: 99%

Impaired homeostasis and phenotypic abnormalities in Prdx6−/−mice lens epithelial cells by reactive oxygen species: increased expression and activation of TGFβ

et al. 2005

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PRDX6, a member of the peroxiredoxins (PRDXs) family, is a key player in the removal of reactive oxygen species (ROS). Using targeted inactivation of the Prdx6 gene, we present evidence that the corresponding protein offsets the deleterious effects of ROS on lens epithelial cells (LECs) and regulates gene expression by limiting its levels. PRDX6-depleted LECs displayed phenotypic alterations and elevated a-smooth muscle actin and big-h3 expression (markers for cataractogenesis), indistinguishable from transforming growth factor b (TGFb)-induced changes. Biochemical assays disclosed enhanced levels of ROS, as well as high expression and activation of TGFb1 in Prdx6 À/À LECs. A CAT assay revealed transcriptional repression of lens epithelium-derived growth factor (LEDGF), HSP27, and aB-crystallin promoter activities in these cells. A gel mobility shift assay demonstrated the attenuation of LEDGF binding to heat shock or stress response elements present in these genes. A supply of PRDX6 toPrdx6 À/À LECs reversed these changes. Based on the above data, we propose a rheostat role for PRDX6 in regulating gene expression by controlling the ROS level to maintain cellular homeostasis.

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Reversing the Inactivation of Peroxiredoxins Caused by Cysteine Sulfinic Acid Formation

Cited by 512 publications

References 25 publications

Hydrogen peroxide produced by Aplysia ink toxin kills tumor cells independent of apoptosis via peroxiredoxin I sensitive pathways

Hydrogen peroxide produced by Aplysia ink toxin kills tumor cells independent of apoptosis via peroxiredoxin I sensitive pathways

Inactivation of oxidized andS-nitrosylated mitochondrial proteins in alcoholic fatty liver of rats

Impaired homeostasis and phenotypic abnormalities in Prdx6−/−mice lens epithelial cells by reactive oxygen species: increased expression and activation of TGFβ

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