Nonspecific lipid transfer protein (sterol carrier protein-2) defective in patients with deficient peroxisomes.
The biosynthesis and intracellular localization of nonspecific lipid transfer protein (nsLTP) in control human subjects and in patients with peroxisome-deficient disorders were investigated. The molecular mass of human nsLTP was indistinguishable from that of rat nsLTP (13 kDa) by immunoblot analysis. Intracellular localization was identical with that of catalase, a marker enzyme of peroxisomal matrix, by a double immunofluorescence study. The nsLTP was deficient in liver tissues or fibroblasts from patients with peroxisome-deficient disorders such as Zellweger syndrome and neonatal adrenoleukodystrophy (ALD). Pulse-chase experiments showed that nsLTP was synthesized as a large precursor in both the control and Zellweger fibroblasts. However, the processing to the 13 kDa mature protein was disturbed and the degradation was rapid in Zellweger fibroblasts. After somatic cell fusion using Zellweger fibroblasts from different genetic groups, the processing was normalized. These results suggest that the biosynthesis and localization of human nsLTP are similar to those of rat nsLTP and that the defect of nsLTP in peroxisome-deficient disorders is a phenomenon secondary to an abnormal transport mechanism of peroxisomal proteins. The defect of nsLTP may play an important role in metabolic disturbances in bile acid synthesis and steroidogenesis in peroxisome-deficient disorders.
Suzuki
Y
Y
Department of Pediatrics, Gifu University School of Medicine, Japan.
Yamaguchi
S
S
Orii
T
T
Tsuneoka
M
M
Tashiro
Y
Y
D001706:Biopsy; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D050356:Lipid Metabolism; D008052:Lipid Metabolism, Inborn Errors / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008715:Methionine / Q000378:metabolism; D008830:Microbodies / Q000378:metabolism* / Q000648:ultrastructure; D010940:Plant Proteins; D011233:Precipitin Tests; D013462:Sulfur Radioisotopes
D002352:Carrier Proteins; D010940:Plant Proteins; D013462:Sulfur Radioisotopes; C072087:sterol carrier proteins; D008715:Methionine; D002374:Catalase