Characterization of the murine gene encoding 1-Cys peroxiredoxin and identification of highly homologous genes

Lee, Tae‐Hoon; Yu, Seong Lan; Kim, Sun-Uk; Kim, Yong Man; Choi, In Pyo; Kang, Sang Won; Rhee, Sue Goo; Yu, Dae Yeul

doi:10.1016/s0378-1119(99)00190-0

Cited by 34 publications

(27 citation statements)

References 21 publications

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“…Subsequent study with more reactive antibodies and by measurement of mRNA expression have demonstrated wide-spread distribution in essentially all organs and essentially all cell types (53). Consistent with the initial observations, the expression level of Prdx6 mRNA and protein is greatest in the lung with high levels of expression also seen brain, testis, kidney, and liver (25,37,49,50,60). A previous report suggesting highest expression levels for the mRNA in mouse liver may have been skewed by the use of bactin in normalization for comparison of different tissues (94); the liver content of b-actin is relatively low so that normalization would result in an inaccurately high value.…”

Section: Tissue Distributionsupporting

confidence: 59%

Peroxiredoxin 6: A Bifunctional Enzyme with Glutathione Peroxidase and Phospholipase A₂Activities

Fisher

2011

Antioxidants & Redox Signaling

337

327

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Peroxiredoxin 6 (Prdx6) is the prototype and the only mammalian 1-Cys member of the Prdx family. Major differences from 2-Cys Prdxs include the use of glutathione (GSH) instead of thioredoxin as the physiological reductant, heterodimerization with pGSH S-transferase as part of the catalytic cycle, and the ability either to reduce the oxidized sn-2 fatty acyl group of phospholipids (peroxidase activity) or to hydrolyze the sn-2 ester (alkyl) bond of phospholipids (phospholipase A 2 [PLA 2 ] activity). The bifunctional protein has separate active sites for peroxidase (C47, R132, H39) and PLA 2 (S32, D140, H26) activities. These activities are dependent on binding of the protein to phospholipids at acidic pH and to oxidized phospholipids at cytosolic pH. Prdx6 can be phosphorylated by MAP kinases at T177, which markedly increases its PLA 2 activity and broadens its pH-activity spectrum. Prdx6 is primarily cytosolic but also is targeted to acidic organelles (lysosomes, lamellar bodies) by a specific targeting sequence (amino acids 31-40). Oxidant stress and keratinocyte growth factor are potent regulators of Prdx6 gene expression. Prdx6 has important roles in both antioxidant defense based on its ability to reduce peroxidized membrane phospholipids and in phospholipid homeostasis based on its ability to generate lysophospholipid substrate for the remodeling pathway of phospholipid synthesis. Antioxid. Redox Signal. 15, 831-844.

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Section: Tissue Distributionsupporting

confidence: 59%

Peroxiredoxin 6: A Bifunctional Enzyme with Glutathione Peroxidase and Phospholipase A₂Activities

Fisher

2011

Antioxidants & Redox Signaling

337

327

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“…However, previous studies have indicated that redox-sensitive transcription factors such as NF-B and activator protein-1 may be important in regulating the expression of some antioxidant enzymes (8,19). The promoter region of the murine 1-cysPrx gene has sequences that are compatible with recognition sites for these transcription factors (15), although there have not yet been definitive studies to confirm their role.…”

Section: Discussionmentioning

confidence: 99%

“…antioxidant enzyme; reactive oxygen species; gene regulation; lung injury OXIDATIVE STRESS HAS BEEN implicated in the pathogenesis of acute respiratory distress syndrome, asthma, lung fibrosis, bronchopulmonary dysplasia, and other lung pathologies (5,15,16). Because pulmonary epithelial cells are essential to maintain function of the alveolar-capillary barrier, their capacity to reduce reactive oxygen species (ROS) associated with oxidative stress is important to prevent the loss of cellular integrity.…”

mentioning

confidence: 99%

Induction of 1-cys peroxiredoxin expression by oxidative stress in lung epithelial cells

Kim¹,

Manevich²,

Feinstein³

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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1-Cys peroxiredoxin (1-cysPrx), a member of the peroxiredoxin family that contains a single conserved cysteine residue, reduces a broad spectrum of hydroperoxides. We studied changes in 1-cysPrx expression in rat lungs and lung cell lines in response to oxidative stress due to hyperoxia, H2O2, or paraquat. After 60 h of hyperoxia (>95% O2), mRNA and protein levels of 1-cysPrx and peroxidase activity were significantly elevated in rat lungs by ∼1.5- to 2-fold compared with the control ( P < 0.05). A similar induction of 1-cysPrx was observed in mouse lungs following exposure to O2 for 63 or 72 h; enzyme induction in mouse lungs was similar for wild-type and glutathione peroxidase 1 gene-targeted mice. H2O2 and paraquat treatment induced 1-cysPrx gene expression in L2 cells. Enzyme induction was attenuated by pretreatment with Trolox or N-acetylcysteine. Actinomycin D treatment showed that stability of 1-cysPrx mRNA was not altered in the presence of H2O2 or paraquat, indicating that increased expression with oxidative stress is regulated at the transcriptional level. These data indicate that the antioxidant enzyme 1-cysPrx is induced in lung cells by oxidative stress.

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“…Prdx6 is mostly cytosolic but is also found in the nucleus (23). Its promoter is regulated by factors responding to oxidative stress (21,26,29).…”

Section: Discussionmentioning

confidence: 99%

Saitohin, Which Is Nested in the tau Locus and Confers Allele-specific Susceptibility to Several Neurodegenerative Diseases, Interacts with Peroxiredoxin 6

Gao

Tse

Conrad

et al. 2005

Journal of Biological Chemistry

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Saitohin is a gene unique to humans and their closest relatives, the function of which is not yet known. Saitohin contains a single polymorphism (Q7R), and its Q and R alleles belong to the H1 and H2 tau haplotype, respectively. The Saitohin Q allele confers susceptibility to several neurodegenerative diseases. To get a handle on Saitohin function, we used it as a bait in a yeast two-hybrid screen. By this assay and subsequent co-immunoprecipitation and glutathione S-transferase pull-down assays, we discovered and confirmed that Saitohin interacts with peroxiredoxin 6, a unique member of that family that is bifunctional and the levels of which increase in Pick disease. The strength of the interaction appeared to be allelespecific, giving the first distinction between the two forms of Saitohin. Saitohin (STH),2 an intronless gene encoding an open reading frame of 128 amino acids, is located in the intron between exons 9 and 10 of the human tau gene (1). It bears no obvious homology to any known protein or motif, and its expression pattern is very similar to that of tau in human tissues. The DNA sequences homologous to the human STH gene reveal an intact, highly conserved open reading frame in the primates most closely related to humans (chimpanzee, bonobo, and gorilla) but not in other primates or in rodents (2, 3). STH provides an evolutionary locus that separates humans and their closest relatives from other mammals.A single nucleotide polymorphism of human STH has been identified that changes glutamine residue 7 to arginine (Q7R (1)). This polymorphism is associated with the two tau gene haplotypes: the Q allele with H1, the R allele with H2 (2, 4). The Q allele is the most common haplotype in humans, but all nonhuman primates are homozygous for the R allele, which makes the Q allele a human-specific marker (2, 3). Hence, the R allele is the ancestral haplotype, whereas the Q allele evolved after the human lineages separated from the other primates.In addition to evolution studies, the R allele of STH was initially found to be associated with Alzheimer disease (1), although subsequent data showing association of the R allele with Alzheimer disease have been inconsistent (2, 4 -10). Recent work may have resolved the conflicting results by indicating that the R allele is associated with Alzheimer disease specifically resulting from the ApoE4 susceptibility factor (11). Furthermore, the Q allele has been shown to be over-represented in several neurodegenerative diseases: progressive supranuclear palsy (12, 13), frontotemporal dementia (4), and Parkinson disease (14). Taken together, these results suggest that identifying a function of STH could implicate several proteins and/or pathway(s) as potential contributors in these neurodegenerative diseases as well.To discover putative functions of STH, we used it as a bait in a yeast two-hybrid screening. We discovered that it interacts with a unique member of the peroxiredoxin family, peroxiredoxin 6 (Prdx6), which has both an antioxidant function and phospholipase act...

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Characterization of the murine gene encoding 1-Cys peroxiredoxin and identification of highly homologous genes

Cited by 34 publications

References 21 publications

Peroxiredoxin 6: A Bifunctional Enzyme with Glutathione Peroxidase and Phospholipase A₂Activities

Peroxiredoxin 6: A Bifunctional Enzyme with Glutathione Peroxidase and Phospholipase A₂Activities

Induction of 1-cys peroxiredoxin expression by oxidative stress in lung epithelial cells

Saitohin, Which Is Nested in the tau Locus and Confers Allele-specific Susceptibility to Several Neurodegenerative Diseases, Interacts with Peroxiredoxin 6

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Characterization of the murine gene encoding 1-Cys peroxiredoxin and identification of highly homologous genes

Cited by 34 publications

References 21 publications

Peroxiredoxin 6: A Bifunctional Enzyme with Glutathione Peroxidase and Phospholipase A2Activities

Peroxiredoxin 6: A Bifunctional Enzyme with Glutathione Peroxidase and Phospholipase A2Activities

Induction of 1-cys peroxiredoxin expression by oxidative stress in lung epithelial cells

Saitohin, Which Is Nested in the tau Locus and Confers Allele-specific Susceptibility to Several Neurodegenerative Diseases, Interacts with Peroxiredoxin 6

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Peroxiredoxin 6: A Bifunctional Enzyme with Glutathione Peroxidase and Phospholipase A₂Activities

Peroxiredoxin 6: A Bifunctional Enzyme with Glutathione Peroxidase and Phospholipase A₂Activities