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-hydroxyn onenal (HNE), was studied in suspensions of mouse thymocytes. Thymocyt es are characterized by low lipid peroxidation in comparison with othe r cell types notwithstanding their high content of arachidonic acid, I n our study a very high capacity of HNE metabolism in thymocytes was o bserved: 27.7 nmol/mg w.w./min, That is about the same HNE degradation rate as determined in liver cells or small intestinal enterocytes, wh ich 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 th ymocytes were identified and quantified after the addition of 100 mu M HNE to thymocyte suspensions: the glutathione-HNE conjugate, the hydr oxynonenoic acid, the 1, 4-dihydroxynonene water, and the glutathione- dihydroxynonene conjugate, Furthermore, the HNE binding to proteins wa s measured, The very rapid HNE degradation in thymocytes besides the h igh 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 cell s.