Identification of a 28 kDa secretory protein from rat olfactory epithelium as a thiol-specific antioxidant

Peshenko, Igor V.; Новоселов, В. И.; Evdokimov, V. A.; Nikolaev, Yu.V.; Kamzalov, Sergey; Shuvaeva, T. M.; Липкин, В. М.; Фесенко, Е. Е.

doi:10.1016/s0891-5849(98)00111-7

Cited by 52 publications

(28 citation statements)

References 34 publications

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“…Initial studies indicated that GSH could function as a reductant with 1-cysPrx isolated from bovine eye (20) or rat olfactory epithelium (21), although the latter result subsequently could not be reproduced (22). Studies with recombinant protein also have been inconclusive because GSH has been effective in some studies (7,23) but not in others (6).…”

Section: Resultsmentioning

confidence: 99%

1-Cys peroxiredoxin overexpression protects cells against phospholipid peroxidation-mediated membrane damage

Manevich

Sweitzer

Pak

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

196

169

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1-Cys peroxiredoxin (1-cysPrx) is a novel antioxidant enzyme able to reduce phospholipid hydroperoxides in vitro by using glutathione as a reductant. This enzyme is widely expressed and is enriched in lungs. A fusion protein of green fluorescent protein with 1-cysPrx was stably expressed in a lung-derived cell line (NCI-H441) lacking endogenous enzyme. Overexpressing cells (C17 or C48) degraded H 2O2 and t-butylhydroperoxide more rapidly and showed decreased sensitivity to oxidant stress as measured by 51

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Section: Resultsmentioning

confidence: 99%

1-Cys peroxiredoxin overexpression protects cells against phospholipid peroxidation-mediated membrane damage

Manevich

Sweitzer

Pak

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

196

169

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“…The two oxidized Cys-47 in the homodimer are separated by Ϸ32 Å, preventing their interaction (22). Native or recombinant purified 1-cysPrx lost activity after interaction with peroxides (5,24,25), presumably reflecting generation of the stable oxidized homodimer (22).…”

mentioning

confidence: 99%

“…Native protein isolated from the bovine eye (26) and rat olfactory mucosa (24) showed activity with glutathione (GSH). However, subsequent studies with native rat protein (25) or recombinant human or bovine protein (5,27) found that GSH was ineffective.…”

mentioning

confidence: 99%

Activation of the antioxidant enzyme 1-CYS peroxiredoxin requires glutathionylation mediated by heterodimerization with πGST

Manevich

Feinstein

Fisher

2004

Proc. Natl. Acad. Sci. U.S.A.

321

266

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1-cys peroxiredoxin (1-cysPrx), a member of the peroxiredoxin superfamily, can protect cells against membrane oxidation through glutathione (GSH)-dependent reduction of phospholipid hydroperoxides to corresponding alcohols. However, purified native or recombinant enzyme in vitro generally lacks GSH peroxidase (GPx) activity because of oxidation of its single conserved cysteine. Reduction of the resultant oxidized cysteine is difficult because of its protected location within the homodimer formed by the oxidized protein monomers. Partial purification of 1-cysPrx from bovine lung revealed the presence of GST in an active preparation, while purification to homogeneity yielded enzyme that inactivated with time. We show that heterodimerization of 1-cysPrx with GSH-saturated GST results in glutathionylation of the oxidized cysteine in 1-cysPrx followed by subsequent spontaneous reduction of the mixed disulfide and restoration of enzymatic activity. Maximum activation of 1-cysPrx occurred with a 1:1 molar ratio of GSH-saturated GST and a 2:1 molar ratio of GSH to 1-cysPrx. Liposome-mediated delivery of oxidized recombinant enzyme into NCI-H441 cells that lack 1-cysPrx but express GST resulted in 1-cysPrx activation, whereas activation in MCF7 cells required co-delivery of GST. Our data indicate a physiological mechanism for glutathionylation of the oxidized catalytic cysteine of 1-cysPrx by its heterodimerization with GST followed by its GSH-mediated reduction and enzyme activation. P eroxiredoxins are a superfamily of nonheme and nonselenium peroxidases that are widely distributed throughout all phyla (1-4). Of the six mammalian peroxiredoxins, five (Prx I-V) contain two conserved cysteines that participate in intramolecular disulfide͞sulfhydryl redox cycling with thioredoxin resulting in reduction of H 2 O 2 and organic hydroperoxides into corresponding alcohols (2). By contrast, 1-cys peroxiredoxin (1-cysPrx or Prx VI) † has a single conserved cysteine (5) and does not use thioredoxin as reductant (5, 6). This peroxiredoxin is expressed in all tissues but at particularly high levels in brain, eye, testes, and lung (2,7,8). Expression of 1-cysPrx protein or mRNA is decreased in a mouse that is susceptible to experimental atherosclerosis (9) and is elevated in brains of patients with Parkinsonian dementia (10), sporadic Creutzfeldt-Jacob disease (11), and Pick disease (12), in lungs from newborns (13), in malignant mesothelioma (14), in the healing edge of skin wounds (15), and in experimental cellular premature senescence (16). 1-cysPrx can reduce phospholipid and other hydroperoxides (6) and protects against cellular membrane damage (17, 18). This enzyme has phospholipase A 2 activity (19), participates in the activation of neutrophil NADPH oxidase through its interaction with p67 phox (20), and prevent methemoglobin formation in erythrocyte hemolysates (21).1-cysPrx catalysis results in the peroxide-mediated oxidation of its Cys-47 to sulfenic acid as deduced from 1-cysPrx crystallization (22). Reduction of the sul...

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“…1-cysPrx, also named peroxiredoxin VI, is a member of this superfamily that can reduce phospholipid hydroperoxides (PLOOH) as well as organic peroxides and H 2 O 2 (1-3). 1-cysPrx has been isolated from bovine ciliary epithelium (4,5), rat olfactory epithelium (6,7), and rat and bovine lungs (8,9); Northern and immunoblot analyses of mammalian tissues show the presence of 1-cysPrx in all organs with especially high levels of 1-cysPrx protein and mRNA expression in lung (8,10). 1-cysPrx is a bifunctional enzyme with both glutathione peroxidase (GPx) and phospholipase A 2 (PLA 2 ) activities (3).…”

mentioning

confidence: 99%

An Antisense Oligonucleotide to 1-cys Peroxiredoxin Causes Lipid Peroxidation and Apoptosis in Lung Epithelial Cells

Pak

Manevich

Kim

et al. 2002

Journal of Biological Chemistry

108

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Identification of a 28 kDa secretory protein from rat olfactory epithelium as a thiol-specific antioxidant

Cited by 52 publications

References 34 publications

1-Cys peroxiredoxin overexpression protects cells against phospholipid peroxidation-mediated membrane damage

1-Cys peroxiredoxin overexpression protects cells against phospholipid peroxidation-mediated membrane damage

Activation of the antioxidant enzyme 1-CYS peroxiredoxin requires glutathionylation mediated by heterodimerization with πGST

An Antisense Oligonucleotide to 1-cys Peroxiredoxin Causes Lipid Peroxidation and Apoptosis in Lung Epithelial Cells

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