BIOSYNTHESIS AND METABOLISM OF 4-HYDROXYNONENAL IN CANINE CEROID-LIPOFUSCINOSIS

Canine ceroid-lipofuscinosis (CCL) is a model of the juvenile type of Batten disease in human patients, Abnormalities have been reported pre viously in 4-hydroxynonenal (HNE) levels in English setters with CCL, The purpose of this study was to examine the sources of HNE in neutrop hil membranes and plasma of CCL dogs, The fatty acid composition of ne utrophil phospholipids, i.e., phosphatidyl ethanolamine and phosphatid yl serine, was determined by gas-liquid-chromatography (GLC) since som e polyunsaturated fatty acids (PUFA) are precursors of HNE. The copper catalyzed peroxidation of low density lipoprotein (LDL) was examined to determine the susceptibility of LDL from CCL dogs to peroxidation, The results indicated that a number of PUFA precursors of HNE decrease d in affected and carrier neutrophil phospholipids, indicating that th is source of HNE may be disease specific, The Cu++ catalyzed formation of HNE from LDL demonstrated that carrier and normal LDL produced lar ge amounts of HNE, while LDL from affected dogs required much higher c oncentrations of Cu++ for maximal HNE production, These results provid e additional support for the role of HNE in the pathogenetic events in NCL and support the view that lipid peroxidation may be an important contributor to the complex pathogenesis of the NCL. (C) 1995 Wiley-Lis s, Inc.