Metabolism of the Lipid Peroxidation Product, 4-Hydroxy-trans-2-nonenal, in Isolated Perfused Rat Heart
作者： Sanjay Srivastava , Animesh Chandra , Li-Fei Wang , William E. Seifert , Beverly B. DaGue
关键词: Sorbinil 、 Aldehyde dehydrogenase 、 Aldose reductase 、 Metabolism 、 Aldose 、 Glutathione 、 Lipid peroxidation 、 Chromatography 、 Electrospray ionization 、 Chemistry 、 Biochemistry
摘要: 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 radioactive metabolites recovered from [3H]HNE-treated hearts revealed four major peaks. Based on the retention times synthesized standards, peak I, which accounted for 20% radioactivity administered to heart, identified be due glutathione conjugates HNE. Peaks II and III, containing 2 37% radioactivity, were assigned 1,4-dihydroxy-2-nonene (DHN) 4-hydroxy-2-nonenoic acid, respectively. Peak IV unmetabolized electrospray ionization mass spectrum I two prominent with m/z values corresponding [M + H]+ HNE DHN glutathione. presence acid III substantiated using gas chromatography-chemical spectroscopy. When exposed sorbinil, inhibitor aldose reductase, no GS-DHN coronary effluent, treatment cyanamide, dehydrogenase, attenuated formation. These results show that metabolic transformations heart involve conjugation oxidation acid. Further GS-HNE conjugate involves reductase-mediated reduction, a reaction catalyzed vitro by homogenous cardiac reductase.
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