Metabolism of the lipid peroxidation product, 4-hydroxy-trans-2-nonenal, in isolated perfused rat heart

Sanjay Srivastava, Animesh Chandra, Li Fei Wang, William E. Seifert, Beverly B. DaGue, Naseem Ansari, Satish Srivastava, Aruni Bhatnagar

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Abstract

The metabolism of 4-hydroxy-trans-2-nonenal (HNE), an α,β-unsaturated aldehyde generated during lipid peroxidation, was studied in isolated perfused rat hearts. High performance liquid chromatography separation of radioactive metabolites recovered from [3H]HNE-treated hearts revealed four major peaks. Based on the retention times of synthesized standards, peak I, which accounted for 20% radioactivity administered to the heart, was identified to be due to glutathione conjugates of HNE. Peaks II and III, containing 2 and 37% radioactivity, were assigned to 1,4-dihydrexy-2-nonene (DHN) and 4-hydroxy-2-nonenoic acid, respectively. Peak IV was due to unmetabolized HNE. The electrospray ionization mass spectrum of peak I revealed two prominent metabolites with m/z values corresponding to [M + H]+ of HNE and DHN conjugates with glutathione. The presence of 4-hydroxy-2- nonenoic acid in peak III was substantiated using gas chromatography-chemical ionization mass spectroscopy. When exposed to sorbinil, an inhibitor of aldose reductase, no GS-DHN was recovered in the coronary effluent, and treatment with cyanamide, an inhibitor of aldehyde dehydrogenase, attenuated 4-hydroxy-2-nonenoic acid formation. These results show that the major metabolic transformations of HNE in rat heart involve conjugation with glutathione and oxidation to 4-hydroxy-2-nonenoic acid. Further metabolism of the GS-HNE conjugate involves aldose reductase-mediated reduction, a reaction catalyzed in vitro by homogenous cardiac aldose reductase.

Original languageEnglish
Pages (from-to)10893-10900
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number18
DOIs
StatePublished - May 1 1998

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Metabolism
Lipid Peroxidation
Rats
Lipids
Aldehyde Reductase
Glutathione
Radioactivity
Metabolites
Cyanamide
Electrospray ionization
Aldehyde Dehydrogenase
High performance liquid chromatography
2-nonenal
4-hydroxy-2-nonenal
Aldehydes
Gas chromatography
Gas Chromatography
Ionization
Effluents
Mass Spectrometry

ASJC Scopus subject areas

  • Biochemistry

Cite this

Srivastava, S., Chandra, A., Wang, L. F., Seifert, W. E., DaGue, B. B., Ansari, N., ... Bhatnagar, A. (1998). Metabolism of the lipid peroxidation product, 4-hydroxy-trans-2-nonenal, in isolated perfused rat heart. Journal of Biological Chemistry, 273(18), 10893-10900. https://doi.org/10.1074/jbc.273.18.10893

Metabolism of the lipid peroxidation product, 4-hydroxy-trans-2-nonenal, in isolated perfused rat heart. / Srivastava, Sanjay; Chandra, Animesh; Wang, Li Fei; Seifert, William E.; DaGue, Beverly B.; Ansari, Naseem; Srivastava, Satish; Bhatnagar, Aruni.

In: Journal of Biological Chemistry, Vol. 273, No. 18, 01.05.1998, p. 10893-10900.

Research output: Contribution to journalArticle

Srivastava, S, Chandra, A, Wang, LF, Seifert, WE, DaGue, BB, Ansari, N, Srivastava, S & Bhatnagar, A 1998, 'Metabolism of the lipid peroxidation product, 4-hydroxy-trans-2-nonenal, in isolated perfused rat heart', Journal of Biological Chemistry, vol. 273, no. 18, pp. 10893-10900. https://doi.org/10.1074/jbc.273.18.10893
Srivastava, Sanjay ; Chandra, Animesh ; Wang, Li Fei ; Seifert, William E. ; DaGue, Beverly B. ; Ansari, Naseem ; Srivastava, Satish ; Bhatnagar, Aruni. / Metabolism of the lipid peroxidation product, 4-hydroxy-trans-2-nonenal, in isolated perfused rat heart. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 18. pp. 10893-10900.
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abstract = "The metabolism of 4-hydroxy-trans-2-nonenal (HNE), an α,β-unsaturated aldehyde generated during lipid peroxidation, was studied in isolated perfused rat hearts. High performance liquid chromatography separation of radioactive metabolites recovered from [3H]HNE-treated hearts revealed four major peaks. Based on the retention times of synthesized standards, peak I, which accounted for 20{\%} radioactivity administered to the heart, was identified to be due to glutathione conjugates of HNE. Peaks II and III, containing 2 and 37{\%} radioactivity, were assigned to 1,4-dihydrexy-2-nonene (DHN) and 4-hydroxy-2-nonenoic acid, respectively. Peak IV was due to unmetabolized HNE. The electrospray ionization mass spectrum of peak I revealed two prominent metabolites with m/z values corresponding to [M + H]+ of HNE and DHN conjugates with glutathione. The presence of 4-hydroxy-2- nonenoic acid in peak III was substantiated using gas chromatography-chemical ionization mass spectroscopy. When exposed to sorbinil, an inhibitor of aldose reductase, no GS-DHN was recovered in the coronary effluent, and treatment with cyanamide, an inhibitor of aldehyde dehydrogenase, attenuated 4-hydroxy-2-nonenoic acid formation. These results show that the major metabolic transformations of HNE in rat heart involve conjugation with glutathione and oxidation to 4-hydroxy-2-nonenoic acid. Further metabolism of the GS-HNE conjugate involves aldose reductase-mediated reduction, a reaction catalyzed in vitro by homogenous cardiac aldose reductase.",
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