ubiquinone and Neuronal-Ceroid-Lipofuscinoses

The juvenile type of neuronal ceroid lipofuscinosis (JNCL) is a recessively inherited, progressive neurodegenerative disease. In this study the levels of the antioxidant factors coenzyme Q10 (CoQ10) and vitamin E (alpha-tocopherol) were measured in plasma samples of 29 JNCL patients and compared to 48 healthy controls. A significant reduction of the coenzyme Q10 level (0.59 +/- 0.25 microgram/ml) was observed in JNCL patients when compared to control subjects (0.80 +/- 0.26 microgram/ml). The level of vitamin E was also reduced markedly in JNCL patients when compared to controls (10.4 +/- 4.1 and 12.1 +/- 4.5 micrograms/ml, respectively). The low levels of CoQ10 and vitamin E in JNCL patients may indicate an impaired antioxidant protection in this disease.

Topics: Adolescent; Adult; Antioxidants; Child; Child, Preschool; Cholesterol; Coenzymes; Humans; Neuronal Ceroid-Lipofuscinoses; Ubiquinone; Vitamin E

The ceroid lipofuscinoses are inherited lysosomal diseases of children characterized by a fluorescent lipopigment stored in a variety of tissues. Defects in lipid metabolism or the control of lipid peroxidation have been postulated to explain their pathogenesis. In the present study, lipopigment was isolated from the liver of sheep affected with ceroid lipofuscinosis. It was 70% protein, the rest being mainly lipids. These were only one-sixth as fluorescent as total liver lipids, but contained a number of fluorophors. None were major components of the lipopigment or the postulated fluorescent product of lipid peroxidation. Lipopigment lipids included the lysosomal marker bis(monoacylglycero)phosphate that contained 42.9% linoleate and 16.5% linolenate. Lipopigment neutral lipids were dolichol, dolichyl esters, ubiquinone, free fatty acids, and cholesterol, indicative of a lysosomal origin of the lipopigment. Phosphatidylcholine, phosphatidylinositol, phosphatidylserine, and phosphatidylethanolamine were present in proportions and with fatty acid profiles typical of lysosomes. No differences were found between the lipids of total control and affected livers, nor the fatty acid profiles of their phosphatidylcholine, phosphatidylethanolamine, or triglycerides. It is concluded that ovine ceroid lipofuscinosis is not a lipidosis, nor does the lipopigment arise from the abnormal peroxidation of lipids. Strong similarities between the lipopigment and the age pigment lipofuscin were noted.

Topics: Animals; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Disease Models, Animal; Dolichols; Fatty Acids; Fluorescence; Liver; Lysophospholipids; Lysosomes; Magnetic Resonance Spectroscopy; Monoglycerides; Neuronal Ceroid-Lipofuscinoses; Phosphatidic Acids; Phospholipids; Pigments, Biological; Proteins; Sheep; Sheep Diseases; Ubiquinone

Previous studies on the lipopigment from the livers of sheep affected with ceroid lipofuscinosis showed that the disease does not involve a defect in lipid metabolism or abnormal lipid peroxidation and that most of the lipopigment was proteinaceous. In this study, lipopigment was isolated from liver, kidney, pancreas, and brain of affected sheep without the use of proteolytic enzymes. Lipopigment from all tissues was two-thirds protein. Modified silver staining after sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed a major band of Mr = 14,800, heterogeneous material between Mr = 5,000 and 9,000, and a major band of Mr = 3,500. These compounds did not stain for RNA or carbohydrate and were digested by a nuclease-free protease as expected for protein. They are not normal lysosomal proteins. Lipopigment levels of dolichol, ubiquinone, and cholesterol were consistent with the lipopigment being protein-enriched lysosome-derived cytosomes. The presence of the Mr = 3,500 proteins in whole affected tissue homogenates distinguished them from homogenates of normal tissues. It was concluded that low Mr proteins are specifically stored in ovine ceroid lipofuscinosis and that the ceroid lipofuscinoses may result from inherited defects in lysosomal protein catabolism.

Topics: Animals; Brain Chemistry; Cholesterol; Disease Models, Animal; Dolichols; Electrophoresis, Polyacrylamide Gel; Fatty Acids; Fluorescence; Kidney; Lipids; Liver; Lysosomes; Molecular Weight; Neuronal Ceroid-Lipofuscinoses; Pancreas; Phospholipids; Pigments, Biological; Proteins; Sheep; Sheep Diseases; Ubiquinone