Metabolism of 4-hydroxynonenal, a cytotoxic lipid peroxidation product, in thymocytes as an effective secondary antioxidative defense mechanism.

The metabolism of the aldehydic lipid peroxidation product, 4-hydroxynonenal (HNE),was studied in suspensions of mouse thymocytes. Thymocytes are characterized by low lipid peroxidation in comparison with other cell types notwithstanding their high content of arachidonic acid. In our study a very high capacity of HNE metabolism in thymocytes was observed: 27.7 nmol/mg w.w./min. That is about the same HNE degradation rate as determined in liver cells or small intestinal enterocytes, which are the cells with the by far highest capacity for the degradation of HNE and other aldehydic lipid peroxidation products in comparison with other cell types. The primary and secondary HNE metabolites in thymocytes were identified and quantified after the addition of 100 microM HNE to thymocyte suspensions: the glutathione-HNE conjugate, the hydroxynonenoic acid, the 1,4-dihydroxynonene, water, and the glutathione-dihydroxynonene conjugate. Furthermore, the HNE binding to proteins was measured. The very rapid HNE degradation in thymocytes besides the high amounts of lipophilic chain-breaking antioxidants is postulated to be an important secondary antioxidative mechanism and the main factor for the low accumulation of lipid peroxidation products in these cells.1668