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Chemical Compound Review:

CHEMBL1086447 (E)-4-oxonon-2-enal

Synonyms: CHEBI:58972, CHEBI:731366, LMFA06000254, ZINC03604280, AKOS006284470, ...

Lee, S.H. et al., Shibata, T. et al., Akagawa, M. et al., West, J.D. et al., Sowell, J. et al., et al.

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Disease relevance of 4-Oxo-2-nonenal

To identify an oxidized lipid that induces p53 phosphorylation, we conducted a screening of lipid peroxidation products in human neuroblastoma SH-SY5Y cells and identified 4-oxo-2-nonenal (ONE), a recently identified aldehyde originating from the peroxidation of omega6 polyunsaturated fatty acids, as a potential inducer of the p53 phosphorylation [1].

High impact information on 4-Oxo-2-nonenal

Despite the structural identity to the anti-DNA autoantibodies, however, R310 showed only a slight crossreactivity with the native double-stranded DNA, whereas the Ab immunoreactivity was dramatically enhanced by the treatment of the DNA with 4-oxo-2-nonenal (ONE), an analog of HNE [2].
4-Hydroxy-2-nonenal, 4-oxo-2-nonenal, and cyclopentenone prostaglandin A and J, which all contain alpha,beta-unsaturated carbonyls, inhibited the AMP-kinase kinase activity of cellular LKB1 [3].
We have discovered that synthetic 4-oxo-nonenal or 4-oxo-2-nonenal-generated from 13(S)-hydroperoxyoctadecadienoic acid recognizes the specific amino acid motifs of His75, Ala76, and Lys77 in bovine histone H4 [4].
A structure-activity relationship was established where 4-HNE and 4-hydroperoxynonenal (4-HpNE) enhanced the activity of the PPARbeta/delta subtype while 4-hyroxyhexenal (4-HHE), 4-oxo-2-Nonenal (4-ONE), and trans-4,5-epoxy-2(E)-decenal did not activate this receptor [5].
Lipid peroxidation during oxidative stress leads to increased concentrations of thiol-reactive alpha,beta-unsaturated aldehyde, including 4-hydroxy-2-nonenal (4-HNE) and 4-oxo-2-nonenal (4-ONE) [6].

Chemical compound and disease context of 4-Oxo-2-nonenal

4-Hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE) have been shown here to be toxic to human neuroblastoma cells in culture at low micromolar concentrations [7].

Biological context of 4-Oxo-2-nonenal

Characterization of 4-oxo-2-nonenal as a novel product of lipid peroxidation [8].
The oxidation of polyunsaturated fatty acids during oxidative stress gives rise to a series of toxic alpha,beta-unsaturated aldehydes, including the electrophile 4-hydroxy-2-nonenal (4-HNE) and the related aldehydes, 4-hydroperoxy-2-nonenal (4-HPNE) and 4-oxo-2-nonenal (4-ONE) [9].

Anatomical context of 4-Oxo-2-nonenal

The reaction of 4-oxo-2-nonenal with calf thymus DNA was also shown to result in the formation of substituted ethano adducts A(1) and A(2) and substituted etheno adduct B [10].

Associations of 4-Oxo-2-nonenal with other chemical compounds

Several ascorbyl-LPO product conjugates, resulting from the interaction of ascorbic acid with hydroperoxy octadecadienoic acid in vitro, were identified by tandem MS, including ascorbyl conjugates of HNE, 4-oxo-2-nonenal, and presumably, 12-oxo-9-hydroxy-10-dodecenoic acid [11].
Covalent modifications to 2'-deoxyguanosine by 4-oxo-2-nonenal, a novel product of lipid peroxidation [12].
Characterization of 2'-deoxycytidine adducts derived from 4-oxo-2-nonenal, a novel lipid peroxidation product [13].
Analysis of the reaction between 2'-deoxyadenosine and 4-oxo-2-nonenal by liquid chromatography/mass spectrometry revealed the presence of three major products (adducts A(1), A(2), and B) [10].

References

Identification of a lipid peroxidation product as a potential trigger of the p53 pathway. Shibata, T., Iio, K., Kawai, Y., Shibata, N., Kawaguchi, M., Toi, S., Kobayashi, M., Kobayashi, M., Yamamoto, K., Uchida, K. J. Biol. Chem. (2006) [Pubmed]
Bispecific Abs against modified protein and DNA with oxidized lipids. Akagawa, M., Ito, S., Toyoda, K., Ishii, Y., Tatsuda, E., Shibata, T., Yamaguchi, S., Kawai, Y., Ishino, K., Kishi, Y., Adachi, T., Tsubata, T., Takasaki, Y., Hattori, N., Matsuda, T., Uchida, K. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
Reactive lipid species from cyclooxygenase-2 inactivate tumor suppressor LKB1/STK11: cyclopentenone prostaglandins and 4-hydroxy-2-nonenal covalently modify and inhibit the AMP-kinase kinase that modulates cellular energy homeostasis and protein translation. Wagner, T.M., Mullally, J.E., Fitzpatrick, F.A. J. Biol. Chem. (2006) [Pubmed]
A novel lipid hydroperoxide-derived cyclic covalent modification to histone H4. Oe, T., Arora, J.S., Lee, S.H., Blair, I.A. J. Biol. Chem. (2003) [Pubmed]
The oxidative stress mediator 4-hydroxynonenal is an intracellular agonist of the nuclear receptor peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta). Coleman, J.D., Prabhu, K.S., Thompson, J.T., Reddy, P.S., Peters, J.M., Peterson, B.R., Reddy, C.C., Vanden Heuvel, J.P. Free Radic. Biol. Med. (2007) [Pubmed]
Modification of heat shock protein 90 by 4-hydroxynonenal in a rat model of chronic alcoholic liver disease. Carbone, D.L., Doorn, J.A., Kiebler, Z., Ickes, B.R., Petersen, D.R. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
4-Oxo-2-nonenal is both more neurotoxic and more protein reactive than 4-hydroxy-2-nonenal. Lin, D., Lee, H.G., Liu, Q., Perry, G., Smith, M.A., Sayre, L.M. Chem. Res. Toxicol. (2005) [Pubmed]
Characterization of 4-oxo-2-nonenal as a novel product of lipid peroxidation. Lee, S.H., Blair, I.A. Chem. Res. Toxicol. (2000) [Pubmed]
Induction of apoptosis in colorectal carcinoma cells treated with 4-hydroxy-2-nonenal and structurally related aldehydic products of lipid peroxidation. West, J.D., Ji, C., Duncan, S.T., Amarnath, V., Schneider, C., Rizzo, C.J., Brash, A.R., Marnett, L.J. Chem. Res. Toxicol. (2004) [Pubmed]
Characterization of 2'-deoxyadenosine adducts derived from 4-oxo-2-nonenal, a novel product of lipid peroxidation. Lee, S.H., Rindgen, D., Bible, R.H., Hajdu, E., Blair, I.A. Chem. Res. Toxicol. (2000) [Pubmed]
Vitamin C conjugates of genotoxic lipid peroxidation products: structural characterization and detection in human plasma. Sowell, J., Frei, B., Stevens, J.F. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
Covalent modifications to 2'-deoxyguanosine by 4-oxo-2-nonenal, a novel product of lipid peroxidation. Rindgen, D., Nakajima, M., Wehrli, S., Xu, K., Blair, I.A. Chem. Res. Toxicol. (1999) [Pubmed]
Characterization of 2'-deoxycytidine adducts derived from 4-oxo-2-nonenal, a novel lipid peroxidation product. Pollack, M., Oe, T., Lee, S.H., Silva Elipe, M.V., Arison, B.H., Blair, I.A. Chem. Res. Toxicol. (2003) [Pubmed]

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