Human Carbonyl Reductase Catalyzes Reduction of 4-Oxonon-2-enal

Doorn, Jonathan A.; Maser, Edmund; Blum, Andreas; Claffey, David J.; Petersen, Dennis R.

doi:10.1021/bi049136q

Cited by 78 publications

(80 citation statements)

References 43 publications

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“…4-Oxo-2-nonenol (ONOL) and a glutathione adduct of ONE (GS-ONE) were prepared by the methods of Doorn et al 25) 6-tert-Butyl-2,3-epoxy-5-cyclohexene-1,4-dione (TBE), 26) isocaproaldehyde, 27) HNE 28) and 21-dehydrocortisol 29) were synthesized as described previously.…”

Section: Chemicalsmentioning

confidence: 99%

“…The products were extracted into 20 ml ethyl acetate were identified by TLC as described. 25) Cell Culture Experiments Bovine aortic endothelial cells (BAECs) were generous gift from Taisho Pharmaceutical Co. (Saitama, Japan), and cultured in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum, penicillin (100 U/ml) and streptomycin (100 mg/ml) at 37°C in a humidified incubator containing 5% CO 2 . The construction and transfection of the pGW1 plasmids harbouring the cDNA for AKR1B14 into BAECs were performed as described previously.…”

Section: Chemicalsmentioning

confidence: 99%

See 1 more Smart Citation

Rat Aldose Reductase-Like Protein (AKR1B14) Efficiently Reduces the Lipid Peroxidation Product 4-Oxo-2-nonenal

Endo

Matsunaga

Fujita

et al. 2010

Biological & Pharmaceutical Bulletin

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The aldo-keto reductase (AKR) superfamily is a rapidly growing group of pyridine nucleotide-dependent oxidoreductases that metabolize carbohydrates, steroids, prostaglandins, and other endogenous aldehydes and ketones, as well as xenobiotic compounds.1,2) Aldose reductase (AR), which belongs to the AKR1B subfamily, is a nicotinamide adenine dinucleotide phosphate reduced form (NADPH)-dependent enzyme that catalyses the first step in the polyol pathway and has been implicated in the onset of secondary complications of diabetes in humans.3,4) AR shows broad substrate specificity for various aldehydes and aldoses, and is involved in various physiological roles, including the metabolism of retinoids, steroids and xenobiotics, and defensive mechanisms for oxidative stress. [5][6][7][8] Beside AR, multiple AR-like proteins (ARLPs) that show high sequence similarity (67-71%) to ARs have been identified in human and rodent tissues. While one ARLP (AKR1B10) is ubiquitously expressed in human tissues, 8,9) two ARLPs, androgen-dependent vas deferens protein (AKR1B7) 10) and fibroblast growth factor-inducible protein (AKR1B8), 11) are distributed tissue-specifically in mice. The two mouse ARLPs reduce aldehydes, but are clearly distinct from mouse AR in their poor efficiency in reducing glucose.12,13) AKR1B7 and AKR1B8 differ in their substrate specificity and inhibitor sensitivity. Compared to AKR1B7, 10,12) AKR1B8 exhibits high catalytic efficiency for cytotoxic 4-hydroxynonenal (HNE) derived from lipid peroxidation, 13) but has poor reactivity towards isocaproaldehyde resulting from the side chain cleavage of cholesterol during steroidogenesis.10) AKR1B7 is insensitive to AR inhibitors (ARIs) 10) and exhibits prostaglandin (PG) F 2a synthase activity, which is not detected in the ARI-sensitive AKR1B8. 14)In rats, two ARLPs, AKR1B13 and AKR1B14, have been identified, 15,16) and are thought to be orthologs of mouse AKR1B8 and AKR1B7, respectively, based on high sequence identity of 95% (AKR1B13 versus AKR1B8) and 87% (AKR1B14 versus AKR1B7). AKR1B13 is distributed in almost all rat tissues, and exhibits similar substrate specificity and inhibitor sensitivity to AKR1B8. 17) AKR1B14 and AKR1B7 are similar in their high expression in the adrenal glands and induction by adrenocorticotropic hormone, 10,16,18) but differ in their distribution and gene regulation in other tissues. AKR1B7 is also expressed in mouse vas deferens, intestine and liver, and is up-regulated by androgen, pituitary tropic hormones and agonists of nuclear receptors (liver X receptor-a, pregnane X receptor and constitutive androstane receptor). 10,19,20) In contrast, AKR1B14 is highly expressed in female rat liver through female-specific secretion pattern of growth hormone, 21) and its expression in male rat liver is up-regulated by oxidative stress. 22) Thus, these differences have suggested that AKR1B14 plays a physiological role distinct from its mouse ortholog, AKR1B7. However, there is no report on the detailed properties of AKR1B14, except for its ro...

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Section: Chemicalsmentioning

confidence: 99%

Section: Chemicalsmentioning

confidence: 99%

Rat Aldose Reductase-Like Protein (AKR1B14) Efficiently Reduces the Lipid Peroxidation Product 4-Oxo-2-nonenal

Endo

Matsunaga

Fujita

et al. 2010

Biological & Pharmaceutical Bulletin

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“…Yeast lacking Cbr are viable [63]. Biochemical studies show the enzyme reduces lipid carbonyl groups, which arise from lipid peroxidation during oxidative stress, to alcohols [64], and this may protect neurons from oxidative damage [65]. Upregulation of Cbr3 mRNA in txnrd1-null yeast [32] and mice (Figs 5a, b; Tables 2, S3) might be a reaction to intracellular lipid peroxidation, and thus indicative of intracellular oxidative stress at membrane surfaces.…”

Section: Systems Affected By Txnrd1 Disruptionmentioning

confidence: 99%

“…Txnrd1 catalytic activity requires a pair of cysteines near the N terminus of the protein (Cys 59 and Cys 64 ) and a C-terminal cysteine and selenocysteine, encoded in exon 15 [16]. Alternatively initiated or spliced Txnrd1 mRNAs have been described [41][42][43], in particular from testis [40], a tissue that exhibits particularly promiscuous patterns of transcription [44].…”

Section: Design and Production Of Txnrd1-mutant Micementioning

confidence: 99%

Effects of thioredoxin reductase-1 deletion on embryogenesis and transcriptome

Bondareva¹,

Capecchi²,

Iverson³

et al. 2007

Free Radical Biology and Medicine

102

115

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Thioredoxin reductases (Txnrd)1 maintain intracellular redox homeostasis in most organisms. Metazoans Txnrds also participate in signal transduction. Mouse embryos homozygous for a targeted null mutation of the txnrd1 gene, encoding the cytosolic thioredoxin reductase, were viable at embryonic day 8.5 (E8.5) but not at E9.5. Histology revealed that txnrd1 −/− cells were capable of proliferation and differentiation; however, mutant embryos were smaller than wild-type littermates and failed to gastrulate. In situ marker gene analyses indicated primitive streak mesoderm did not form. Microarray analyses on E7.5 txnrd −/− and txnrd +/+ littermates showed similar mRNA levels for peroxiredoxins, glutathione reductases, mitochondrial Txnrd2, and most markers of cell proliferation. Conversely, mRNAs encoding sulfiredoxin, IGF-binding protein 1, carbonyl reductase 3, glutamate cysteine ligase, glutathione S-transferases, and metallothioneins were more abundant in mutants. Many gene expression responses mirrored those in thioredoxin reductase 1-null yeast; however mice exhibited a novel response within the peroxiredoxin catalytic cycle. Thus, whereas yeast induce peroxiredoxin mRNAs in response to thioredoxin reductase disruption, mice induced sulfiredoxin mRNA. In summary, Txnrd1 was required for correct patterning of the early embryo and progression to later development. Conserved responses to Txnrd1 disruption likely allowed proliferation and limited differentiation of the mutant embryo cells.

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“…Subsequent malfunction or downregulation of this enzyme would be consistent with increased PCO, which, because of the polarity of the carbonyl moiety, could expose normally buried hydrophobic amino acids to the protein surface, resulting in a disruption of conformation. CR has been shown to reduce the lipid peroxidation product, HNE (129). CR expression is altered in DS and AD patients (26).…”

Section: Ead Carbonylated Proteinsmentioning

confidence: 99%

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

Butterfield

Perluigi

Reed

et al. 2012

Antioxidants & Redox Signaling

157

142

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Several studies demonstrated that oxidative damage is a characteristic feature of many neurodegenerative diseases. The accumulation of oxidatively modified proteins may disrupt cellular functions by affecting protein expression, protein turnover, cell signaling, and induction of apoptosis and necrosis, suggesting that protein oxidation could have both physiological and pathological significance. For nearly two decades, our laboratory focused particular attention on studying oxidative damage of proteins and how their chemical modifications induced by reactive oxygen species/reactive nitrogen species correlate with pathology, biochemical alterations, and clinical presentations of Alzheimer's disease. This comprehensive article outlines basic knowledge of oxidative modification of proteins and lipids, followed by the principles of redox proteomics analysis, which also involve recent advances of mass spectrometry technology, and its application to selected age-related neurodegenerative diseases. Redox proteomics results obtained in different diseases and animal models thereof may provide new insights into the main mechanisms involved in the pathogenesis and progression of oxidativestress-related neurodegenerative disorders. Redox proteomics can be considered a multifaceted approach that has the potential to provide insights into the molecular mechanisms of a disease, to find disease markers, as well as to identify potential targets for drug therapy. Considering the importance of a better understanding of the cause/effect of protein dysfunction in the pathogenesis and progression of neurodegenerative disorders, this article provides an overview of the intrinsic power of the redox proteomics approach together with the most significant results obtained by our laboratory and others during almost 10 years of research on neurodegenerative disorders since we initiated the field of redox proteomics. Antioxid. Redox Signal. 17, 1610-1655.

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Human Carbonyl Reductase Catalyzes Reduction of 4-Oxonon-2-enal

Cited by 78 publications

References 43 publications

Rat Aldose Reductase-Like Protein (AKR1B14) Efficiently Reduces the Lipid Peroxidation Product 4-Oxo-2-nonenal

Rat Aldose Reductase-Like Protein (AKR1B14) Efficiently Reduces the Lipid Peroxidation Product 4-Oxo-2-nonenal

Effects of thioredoxin reductase-1 deletion on embryogenesis and transcriptome

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

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