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 H. Ansari, Satish K. Srivastava, Aruni Bhatnagar

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205 Scopus citations

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Srivastava, S., Chandra, A., Wang, L. F., Seifert, W. E., DaGue, B. B., Ansari, N. H., Srivastava, S. K., & 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